Investigation of dose-dependent effects of berberine against renal ischemia/reperfusion injury in experimental diabetic rats

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The data are expressed as mean±standard deviation (* p<0.05 vs. STZ+IRI group. One way ANOVA, post hoc Tukey test)." ] ] ] "textoCompleto" => "IntroductionRenal ischemia/reperfusion injury (IRI) inducing multiple organ dysfunction results in high mortality rates in clinical and experimental studies.<a class="elsevierStyleCrossRefs" href="#bib0255">1–3</a> IRI causes various biochemical and morphological alterations including increased intercellular sodium and calcium concentration, intracellular ATP depletion, oxidative stress, tubular and glomerular damage, inflammation, fibrosis, and cell death via apoptosis or necrosis.<a class="elsevierStyleCrossRefs" href="#bib0265">3–7</a>Diabetes mellitus (DM), common chronic metabolic disorder, is a serious risk factor for ischemic acute renal failure. IRI accompanying by diabetes adversely affects development of severe diabetic nephropathy.<a class="elsevierStyleCrossRefs" href="#bib0290">8–10</a>Berberine (BRB) which is the major active component of Rhizoma Coptidis, has been widely used in Chinese for traditional treatment for diabetes. BRB decreases elevated blood glucose level, and improves insulin sensitivity in diabetic patients and also experimental diabetic animals.<a class="elsevierStyleCrossRefs" href="#bib0305">11,12</a> BRB also has an antioxidant activity against oxidative stress.<a class="elsevierStyleCrossRef" href="#bib0315">13</a> Recently, it has been reported that BRB possesses some additional effects such as anti-inflammatory, anti-bacterial, and anti-viral.<a class="elsevierStyleCrossRefs" href="#bib0315">13–15</a> On the basis of these features, BRB has been used in several studies, especially ischemia/reperfusion studies as a therapeutic agent.The aim of the present study was to explore the most effective therapeutic dose of berberine on renal ischemia/reperfusion injury in streptozotocin-induced diabetic rats by using histopathological and biochemical analysis. To our knowledge, this is the first report related with the dose-dependent therapeutic effects of berberine on renal ischemia/reperfusion in STZ-induced diabetic rats.Materials and methodsDrugs and chemicalsBerberine chloride (BBR) was purchased from Sigma-Aldrich, Germany (B3251). Streptozotocin (STZ; ab142155) was obtained from Abcam, Cambridge, United Kingdom.For enzyme linked immunosorbent assays (ELISA), tumor necrosis factor alpha (TNF-α, ab100785), C reactive protein (CRP, ab108827), lactate dehydrogenase (LDH, ab102526), and creatinine (ab65340) kits were purchased Abcam, Cambridge, United Kingdom while only blood urea nitrogen (BUN, SL1053Ra) was purchased in SunLong Biotech, Hangzhou, Zhejiang, China).Primer antibodies (IgG type rabbit polyclonal antibodies) including Anti-β-actin (ab8227), Anti-Bcl-2 (ab196495) and Anti-Bax (ab32503) antibodies for the Western blot analysis were purchased from Abcam, Cambridge, United Kingdom.Study designAnimalsAnimals were allowed free access to food and water at controlled room temperature (22–25°C) under a 12:12-h day/night cycle for the duration of the study. All procedures were approved by the Animal Care and Use Committee at Bezmialem Vakif University and performed in accordance with institutional guidelines.Thirty male Spraque Dawley rats (Experimental Animal Research Laboratory at Bezmialem Vakif University, Istanbul, Turkey) were divided into five groups as follows: STZ-induced diabetes group (STZ, n=6); STZ-induced diabetes+renal ischemia/reperfusion group (STZ+IRI, n=6); STZ-induced diabetes+renal ischemia/reperfusion+50mg/kg berberine treatment group (STZ+IRI+BRB1, n=6); STZ-induced diabetes+renal ischemia/reperfusion+100mg/kg berberine treatment group 100mg/kg berberine treatment group (STZ+IRI+BRB2, n=6); STZ-induced diabetes+renal ischemia/reperfusion+150mg/kg berberine treatment group (STZ+IRI+BRB3, n=6).Diabetes inductionExperimental diabetes mellitus was induced by a single intraperitoneal injection of STZ at the dose of 50mg/kg. It was prepared in 0.1mol/l citrate buffer (pH 4.5), immediately before use. The blood samples at the 24th hour after STZ injection were obtained from the caudal veins. Rats with a glucose concentration higher than 300mg/dL were considered as diabetic.<a class="elsevierStyleCrossRef" href="#bib0330">16</a>Renal ischemia/reperfusion procedureBilateral renal ischemia model was performed on diabetic rats. Animals were anesthetized with intraperitoneal ketamine (4mg/100g) and xylazine (1.5mg/100g) before the onset of the surgery. All animals were shaved and sterilized. Both left and right kidneys were exposed by lateral incisions. Then, left and right renal arteries and veins were isolated. Renal ischemia was achieved by clamping by left and right renal arteries with vascular clips for 45min.<a class="elsevierStyleCrossRef" href="#bib0335">17</a> At the end of this time, vascular clips were removed, and reperfusion was allowed. Finally, incisions were closed with surgical suture. During the surgical procedure, body temperature was monitored using a Nimomed® infrared thermometer.Berberine administrationBerberine was freshly prepared every day by dissolving in distilled water. The different doses (50mg/kg, 100mg/kg, and 150mg/kg) of berberine were administrated by oral gavage after inducing renal ischemia/reperfusion (IRI). Initial berberine doses were applied at 24th hour after IRI, and daily administrations were made for 14 days. All experimental animals were sacrificed at 24th hour after the all doses were over.Histological analysisEach kidney sample was divided into two equal pieces. One piece was used for histological analyses, the other was used for biochemical analyses. For histological analysis, tissues were fixed in 10% formalin solution and after dehydration, embedded in paraffin. Five-micrometer (μm) sections obtained from paraffin blocks were stained with Harris Hematoxylin (Bio-optica Catalog no. 05-06004/L, Milano, Italy) and Shandon Eosin Y Alcoholic (Thermo scientific, Catalog no. 6766007, Kalamazoo, MI, USA), Masson Trichrome (Bio-optica Catalog no. 04-010802, Milano, Italy), and Periodic Acid Schiff stains (Beslab BS-0040, Turkey). Hematoxylin & Eosin (H&E) staining technique was used for the detection of pathological alterations including proximal/distal tubular atrophy and necrosis, congestion, and infiltration. Masson's trichrome staining technique was used for detecting, and determining the degree of the fibrosis. Periodic Acid Schiff staining technique was used for detecting of the status of the brush border and glomerular basement membrane.Scoring system for evaluation of the kidney injuryTotal kidney injury for each sample was investigated by monitoring proximal tubular damage (proximal tubular dilation and atrophy, loss of brush border, proximal tubular necrosis), distal tubular damage (distal tubular dilation/atrophy and distal tubular necrosis), glomerular damage (glomerular basement membrane thickening), interstitial damage (interstitial fibrosis, hemorrhage, and mononuclear cell filtration) and vascular damage (interstitial congestion). All findings were evaluated and scored as follows: 0=absent (<10%), 1=minimal (10–25%), 2=mild (25–40%), 3=moderate (40–55%), 4: severe (>50%) with a maximum score of 40 for each kidney sample.Sections were scored by two blind observer (Kumas, M and Esrefoglu, M.) using a Nikon Eclipse i5 light microscope with a Nikon DS-Fi1c camera, and Nikon NIS Elements version 4.0 image analysis systems (Nikon Instruments Inc., Tokyo, Japan).Biochemical analysisOxidative stress parametersOxidative stress parameters including total antioxidant status (TAS) and total oxidant status (TOS) levels were determined by using an automatic biochemical analyzer (c800, Abbott, USA). Tissue TAS level was determined by Erel<a class="elsevierStyleCrossRefs" href="#bib0340">18,19</a>. After this assay relied on the ability of antioxidants in the sample to inhibit ABTS (2,2′-azino-di-3-ethylbenz-thiazoline sulfonate) from being oxidized into ABTS+ by a peroxidase metmyoglobin. An antioxidant with a known concentration (1.65mmol/l) was used as the standard to calculate antioxidant levels in the samples. The TAS level was expressed as mmol Trolox equivalent/l (mmol Trolox equiv./l). The tissue TOS level was measured by Erel.<a class="elsevierStyleCrossRefs" href="#bib0345">19,20</a> TOS method which relied on the oxidation of ferrous ions into ferric ions in the presence of various oxidative species in an acidic medium. Ferric ion concentrations were measured by xylenol orange. The assay was calibrated with a standard hydrogen peroxide solution (39.16μmol/l). Results were expressed as μmol H2O2 equivalent/l (μmol H2O2 equiv./l). The TOS/TAS ratio was defined as oxidative stress index (OSI).Immunoblot assaysKidney tissues were homogenized in RIPA buffer (50mmol/l Tris–HCl, pH 7.4, 150mmol/l NaCl, 5mmol/l EDTA, 1% Nonidet P-40, 1% sodium deoxycholate, 0.1% SDS, 1% aprotinin, 50mmol/l NaF, 0.1mmol/l Na3VO4), and proteinase inhibitor cocktail (Merck KGaA, Darmstadt, Germany). After centrifugation at 14,000rpm (Beckman Coulter, Krefeld, Germany) for 10min at 4°C, the final supernatant was used as the total protein. Protein concentrations were determined using the Bradford method, then all protein samples were equilibrated at 40mg/ml with loading buffer (4% SDS, 10% 2-mercaptoethanol, 20% glycerol, 0.004M Tris–HCl, pH 6.8) and loaded 8% and 12% sodium dodecyl sulfate polyacrylamide gel wells as 30μl, transferred onto a polyvinylidene difluoride membrane (PVDF), and then incubated with primary antibodies including Anti-β Actin Anti-Bax, and Anti-Bcl 2 in a solution containing 5% powdered skim milk and 0.05% Triton X-100/TBS, and washed three times in TBS-T for 10min each. Blots were incubated with a horse radish peroxidase (HRP)-conjugated goat anti-rabbit IgG at a concentration of 1μg/ml in 5% powdered skim milk in 0.05% TBS-T. Protein bands were visualized with Pierce ECL Western blotting substrate (Thermo Scientific). Protein bands were visualized using the enhanced chemiluminescence detection system (Vilber Lourmat Fx7, Collégien, France) and analyzed with Image J software.Enzyme-linked ImmunoSorbent Assay (ELISA)Serum and tissue samples were thawed and ELISA kits were used for the quantitative measurement of Rat TNF alpha, CRP, and BUN. Optical density was read on a standard automated plate reader at 450nm (Perkin Elmer, 1420 Victor 3).Assays of lactate dehydrogenase (LDH) and creatinineSerum LDH and creatinine levels were detected by colorimetric method using microplate reader (Perkin Elmer, 1420 Victor 3).Assessment of Na-K-ATPase and Ca-ATPaseNa-K-ATPase and Ca-ATPase levels were measured with ELISA test in kidney tissues. The ELISA assays performed with proteins which isolated from homogenized tissues according to manufacturer's instructions. Results were expressed in nanogram per milliliter of 1mg total protein.Statistical analysisNormality of the all data was tested with Shapiro–Wilk normality test, because of our sample size of less than 50. Data have a normal distribution (Shapiro–Wilk test, p≥0.05) was analyzed by parametric test ANOVA (post hoc Tukey's HSD) for multiple comparisons, while non-normal distributed data (Shapiro–Wilk test, p<0.05) was analyzed by Kruskal–Wallis test for multiple comparison and Mann–Whitney U test for comparing two groups.Values are presented as minimum, maximum and median for non-parametric data, while as mean± standard deviation (SD) for parametric data. p values≤0.05 were approved as statistically significant. Statistical analyses were done with SPSS 20.0 (IBM, New York, USA) and MS Office Excel. Graph Pad Prism 6 was used for drawing bar charts.ResultsWe examined both left and right kidney for histological and biochemical analysis, and compared all results. We did not find any important differences in terms of all evaluated parameters among left and right kidneys. Thus, we preferred to mention only pathological alterations observed in left kidneys.Assessment of histopathological alterationsThe results about histopathological scores of the all of the groups are presented in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>The highest proximal tubular damage scores including tubular dilation and atrophy (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>a), loss of brush border (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>b), and tubular necrosis (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>c) were detected in STZ+IRI group. The median scores of each of those of alterations were also statistically higher in STZ+IRI group than STZ group (p=0.007, p=0.003, and p=0.004, respectively). Proximal tubular damage seen in STZ group was severely aggravated after IRI. 50mg dose of BRB administration was not improved proximal tubular dilation and atrophy, and tubular necrosis in STZ+IRI+BRB1 group (p>0.05, <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>a and b), whereas the loss of brush border score was significantly decreased in that group (p=0.011). All of those alterations improved after 100mg and 150mg BRB administration in STZ+IRI+BRB2 (p=0.004, p=0.003, and p=0.007, respectively; <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>c) and STZ+IRI+BRB3 groups (p=0.004, p=0.003, p=0.004, respectively; <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>d).<elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia>Distal tubular damage including tubular dilation and atrophy (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>a), and tubular necrosis (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>c) severely increased in STZ+IRI group compared to STZ group (p=0.008 and p=0.005, respectively). In both STZ+IRI+BRB2 and STZ+IRI+BRB3 groups, distal tubular dilation and atrophy scores markedly decreased when compared to STZ+IRI group (p=0.012 and p=0.004, respectively; <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>c and d). Distal tubular necrosis score reduced in STZ+IRI+BRB3 (p=0.008; <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>c and d), but it was not detected any statistically significant alteration in other berberine administrated groups (p>0.05). Thyroidization which is the similarity of the tubules, accumulating acidophilic and PAS positive material within the lumen, with thyroid follicles was observed in two sections (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>a). Brown hemosiderin granules accompanied by mononuclear cell infiltration in the necrotic area were also observed (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>c).Glomerular basement membrane seemed to be thickened in STZ+IRI group compared to STZ group (p=0.027, <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>d). Berberine administration was effective in normalization of the basement membrane in STZ+IRI+BRB2 and STZ+IRI+BRB3 (p=0.014, for both). Fibrosis and mononuclear cell infiltration related with interstitial damage were observed in STZ+IRI group. When compared to STZ group, mononuclear cell infiltration score was markedly increased in STZ+IRI group (p=0.008, <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>c and d). Berberine administration at all doses significantly improved those scores (p<0.05). Fibrosis was sometimes observed in STZ+IRI group, but it occupied large area in only one sample (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>c). Berberine administrations had no significant effect on fibrosis.Congestion and dilatation of the capillaries were even for per sample so were collectively scored (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>f). The highest median score was detected in STZ+IRI group (p=0.02). All doses of berberine resulted in decrease in congestion scores (p=0.014, p=0.004, and p=0.003, respectively).The highest total histopathological score was detected in STZ+IRI group (p=0.004). The scores of STZ+IRI+BRB2, and STZ+IRI+BRB3 groups (p=0.004, for both) were lower than that of STZ+IRI group.Assessment of biochemical alterationsThe results of biochemical parameters of all of the groups are represented in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Assessment of kidney functionSerum BUN and creatinine levels which are the markers for kidney functions were evaluated (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). The mean BUN and creatinine levels were markedly higher in STZ+IRI group than that of STZ group. Those levels significantly decreased after berberine administration in all berberine administrated groups (p<0.001), except mean serum creatinine level which was not significantly changed between STZ+IRI+BRB1 and STZ+IRI group (p>0.05).<elsevierMultimedia ident="fig0015"></elsevierMultimedia>Assessment of oxidative stressThe highest mean TOS was detected in STZ+RIR group (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>). The levels in berberine administrated groups were statistically lower than that of STZ+IRI group (p<0.001, for all comparisons). The lowest mean total antioxidant status (TAS) was detected in STZ+IRI group (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>). Berberine administration gradually increased antioxidant status in a dose dependent manner when compared to STZ+RIR group (p<0.001, for all groups).<elsevierMultimedia ident="fig0020"></elsevierMultimedia>Oxidative stress index was calculated as ratio of TOS and TAS. OSI in STZ+IRI group was considerably higher than the other groups (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>). OSI decreased in berberine administrated groups (p<0.001, for all groups). According to these results, berberine markedly suppressed oxidative stress via stimulating antioxidant system.Assessment of lactate dehydrogenaseThe mean serum LDH level which is a marker for tubular necrosis was higher in STZ+IRI group than that of STZ group (p<0.001, <a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a>). The levels in STZ+IRI+BRB1, STZ+IRI+BRB2, and STZ+IRI+BRB3 groups were significantly lower than STZ+IRI group (p<0.001, for all of comparisons).<elsevierMultimedia ident="fig0025"></elsevierMultimedia>Assessment of inflammation markersThe highest mean TNF-α and CRP levels were detected in STZ+IRI group compared to STZ (p<0.001) and the other groups. The levels gradually decreased in berberine administrated groups including STZ+IRI+BRB1, STZ+IRI+BRB2, and STZ+IRI+BRB3 groups (<a class="elsevierStyleCrossRef" href="#fig0030">Fig. 6</a>).<elsevierMultimedia ident="fig0030"></elsevierMultimedia>Berberine significantly showed an anti-inflammatory effect against renal ischemia injury via reducing tissue levels of TNF-α and CRP (p≤0.05).Assessment of apoptosisExpression of pro-apoptotic Bax protein significantly increased but expression of anti-apoptotic Bcl-2 protein decreased in STZ+IRI group compared to the other groups (p<0.001, <a class="elsevierStyleCrossRef" href="#fig0035">Fig. 7</a>). IRI markedly caused apoptosis via inducing pro-apoptotic protein, and suppressing anti-apoptotic protein (p<0.001). Berberine administrations at the doses of 100mg/kg and 150mg/kg increased expression of pro-apoptotic Bcl-2 (p<0.001), but berberine at a dose of 50mg/kg in STZ+IRI+BRB1 did not perform any anti-apoptotic effect compared to STZ+IRI group.<elsevierMultimedia ident="fig0035"></elsevierMultimedia>Assessment of Ca2+ ATPase and Na+/K+-ATPase enzyme activitiesThe mean tissue Ca2+ ATPase enzyme activity was markedly lower in STZ+IRI group than that of STZ group. The highest mean Ca2+ ATPase enzyme activity was detected in STZ+IRI+BRB3. Berberine administration at a dose of 150mg/kg significantly increased that enzyme activity (p<0.01, <a class="elsevierStyleCrossRef" href="#fig0040">Fig. 8</a>). The mean tissue Na+/K+-ATPase enzyme activity was detected as 13.38± 1.21 in STZ group while 10.94±0.47 in STZ+IRI group (p<0.001). The activity of this enzyme in STZ+IRI+BRB2 group was significantly higher than that of STZ+IRI group (p=0.039, <a class="elsevierStyleCrossRef" href="#fig0040">Fig. 8</a>).<elsevierMultimedia ident="fig0040"></elsevierMultimedia>DiscussionAcute kidney injury (AKI) or renal failure has been described as a rapid dysfunction of the kidney. Ischemia/reperfusion injury is the most important reason of acute renal failure.<a class="elsevierStyleCrossRefs" href="#bib0355">21,22</a> Diabetes mellitus is also an important risk factor for the renal failure.<a class="elsevierStyleCrossRef" href="#bib0270">4</a> Animal models have been widely for understanding mechanisms of IRI. It was recorded that IRI has resulted in serious histopathological and biochemical damages in both patients and experimental animals.<a class="elsevierStyleCrossRefs" href="#bib0365">23–25</a>BUN and serum creatinine levels are the most commonly used markers evaluating renal function. Significantly increased BUN and creatinine levels are typical indicators of AKI.<a class="elsevierStyleCrossRefs" href="#bib0380">26–29</a> We detected significantly increased BUN and creatinine levels in ischemic diabetic group. These levels were decreased in BRB administrated groups. Those decreases might show the beneficial effect of berberine on kidney functions.Especially re-oxygenation of tissue after hypoxia seriously causes accumulation of free radicals, known as oxidative stress. Both ischemia and hyperglycemia aggravate production of reactive oxygen species (ROS), and it is possible that the two factors precipitate each other.<a class="elsevierStyleCrossRefs" href="#bib0400">30,31</a> Clinical and experimental studies showed that diabetes increased the degree of ischemic injury.<a class="elsevierStyleCrossRefs" href="#bib0330">16,31,32</a> Measurement of TOS and TAS is a crucial biomarker to evaluate oxidative damage.<a class="elsevierStyleCrossRefs" href="#bib0405">31–33</a> Since tissue TOS level was markedly increased in STZ+IRI group we suggest that IRI induces oxidative stress. Conversely since all doses of BRB decreased TOS level but increased TAS level, we suggest that BRB is effective in reducing oxidative stress and damage induced by IRI in diabetic rats.In the current study, we detected serious histopathological damages including tubular, glomerular, interstitial, and vascular damage in diabetic rats after IRI in accordance with previous studies.<a class="elsevierStyleCrossRefs" href="#bib0270">4,5,10,28</a> Proximal and distal tubular damage was more obvious than glomerular damage as previously reported.<a class="elsevierStyleCrossRefs" href="#bib0420">34–36</a> Endothelial damage in peritubular capillaries caused by vascular congestion, and leukocyte infiltration was reported after IRI.<a class="elsevierStyleCrossRefs" href="#bib0300">10,22,24,25</a> We observed that dilatation and congestion of the capillaries were even for per sample. Mononuclear cell infiltration accompanied by necrosis occupied large area in ischemic group. The glomerular basement membrane in STZ+IRI group was thicker than those of the other groups. BRB, in a dose-dependent manner, improved histopathological findings; the most effective dose was 150mg/kg for tissue healing after IRI. Even the decrease in total pathological score at a dose of 50mg/kg BRB administrated group was evident, it was not statistically significant.Tubular necrosis was obvious in diabetic ischemic group. LDH is an important indicator for necrosis thus increased levels of LDH in serum indicates plasma membrane damage.<a class="elsevierStyleCrossRefs" href="#bib0430">36,37</a> Following IRI, we detected significantly increased LDH levels concomitant with severe tubular damage. Necrotic cell death stimulates inflammatory responses.<a class="elsevierStyleCrossRefs" href="#bib0280">6,22</a> Hence inflammation has been observed generally together with necrosis induced by IRI. TNF-α, TGF-β and CRP have been widely used as inflammation markers. The serum concentrations of those markers increase after acute or chronic renal injury associated with diabetes.<a class="elsevierStyleCrossRefs" href="#bib0390">28,38,39</a> In the present study TNF-α and CRP level in IRI group were markedly increased in diabetic rats. It was mentioned in previous studies that BRB has anti-inflammatory effect via inhibiting inflammatory markers.<a class="elsevierStyleCrossRefs" href="#bib0450">40,41</a> In current study, BRB showed similar anti-inflammatory effect against IRI in all berberine administrated groups via decreasing levels of TNF-α and CRP.Diabetes and ischemia both, significantly induces apoptotic cell death.<a class="elsevierStyleCrossRefs" href="#bib0375">25,42</a> In ischemic tissue, pro-apoptotic Bax protein level significantly increased while anti-apoptotic Bcl2 protein level decreased in diabetic rats. BRB administration at the doses of 100mg/kg and 150mg/kg showed significant anti-apoptotic effect via suppressing anti-apoptotic protein, while BRB administration at a dose of 50mg/kg was not effective as well as other doses. Visnagri et al.<a class="elsevierStyleCrossRef" href="#bib0390">28</a> demonstrated that BRB at the doses of 20mg/kg and 40mg/kg has similar anti-apoptotic effect in non-diabetic rats. During hypoxia, as a result of cellular damage, intracellular calcium level dramatically increases.<a class="elsevierStyleCrossRef" href="#bib0465">43</a> The Ca2+-ATPase(s) enzyme found in the plasma membrane and endoplasmic reticulum has an important role in maintaining the intracellular Ca2+ level.<a class="elsevierStyleCrossRef" href="#bib0470">44</a> In our study Ca2+-ATPase enzyme level significantly decreased after IRI in diabetic rats. We suggest that decrease of Ca2+-ATPase leads to increase of intracellular Ca2+ concentration. Conversely, Visnagri et al.<a class="elsevierStyleCrossRef" href="#bib0390">28</a> have suggested that ischemia induces apoptosis, and Ca2+-ATPase enzyme level increases in ischemic group. We detected decreased levels of Ca2+-ATPase in STZ+IRI group. Increase in intracellular Ca2+ is an indicator of apoptotic cell death.<a class="elsevierStyleCrossRef" href="#bib0475">45</a> Anti-apoptotic Bcl 2 has a crucial function on Ca2+ homeostasis. Bcl-2 overexpression causes decreased Ca2+ releasing from endoplasmic reticulum.<a class="elsevierStyleCrossRef" href="#bib0475">45</a> As we mentioned before, expression of Bcl2 level decreased in ischemic group. Both decreasing of Ca2+-ATPse enzyme and Bcl2 levels indicated that renal tissue cell sustained apoptotic cell death. In contrast to STZ+IRI group, BRB showed anti-apoptotic effect via increasing Ca2+-ATPase enzyme and Bcl 2 protein levels.The Na+/K+-ATPase enzyme, known as energy-dependent sodium pump, transports Na+ into and K+ out of the cell against their concentration gradients.<a class="elsevierStyleCrossRef" href="#bib0480">46</a> This pump is essential for the maintenance of Na+ and K+ concentrations across the membrane. When this pump stops working or destroys, Na+ accumulates in cytoplasm.<a class="elsevierStyleCrossRef" href="#bib0460">42</a> Tubular epithelial cell polarity thus fluid/ion transport are significantly destroyed after IRI. It has been shown in several organs including kidney, myocardium, brain, hippocampus, etc. that ischemia injury resulted in decrease in the levels of Na+/K+-ATPase enzyme.<a class="elsevierStyleCrossRefs" href="#bib0395">29,47–50</a> IRI markedly caused in decline of Na+/K+-ATPase level in diabetic rats, and BRB administration at a dose of 100mg/kg significantly increased that of enzyme level.ConclusionAs a conclusion berberine administration following ischemia/reperfusion markedly improved histopathological findings, prevented necrotic cell death. Berberine normalized kidney function via decreasing BUN and creatinine levels. Berberine showed also anti-oxidant, anti-apoptotic, and anti-inflammatory effect. According to these data we suggest that berberine at the doses of 100 and 150mg may be used as a potential therapeutic agent against renal ischemic injury.Conflict of interestAll authors declared that they have no conflict of interest.FundingThis work was supported by the Bezmialem Vakif University Scientific Research Project Foundation [grant number 6.2017/8]." "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres1256008" "titulo" => "Abstract" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objectives" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1163642" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1256007" "titulo" => "Resumen" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Antecedentes" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivos" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1163641" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Materials and methods" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Drugs and chemicals" ] 1 => array:3 [ "identificador" => "sec0020" "titulo" => "Study design" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0155" "titulo" => "Animals" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Diabetes induction" ] 2 => array:2 [ "identificador" => "sec0035" "titulo" => "Renal ischemia/reperfusion procedure" ] 3 => array:2 [ "identificador" => "sec0040" "titulo" => "Berberine administration" ] ] ] 2 => array:3 [ "identificador" => "sec0045" "titulo" => "Histological analysis" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0050" "titulo" => "Scoring system for evaluation of the kidney injury" ] ] ] 3 => array:3 [ "identificador" => "sec0055" "titulo" => "Biochemical analysis" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0060" "titulo" => "Oxidative stress parameters" ] ] ] 4 => array:3 [ "identificador" => "sec0065" "titulo" => "Immunoblot assays" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0070" "titulo" => "Enzyme-linked ImmunoSorbent Assay (ELISA)" ] 1 => array:2 [ "identificador" => "sec0075" "titulo" => "Assays of lactate dehydrogenase (LDH) and creatinine" ] 2 => array:2 [ "identificador" => "sec0080" "titulo" => "Assessment of Na-K-ATPase and Ca-ATPase" ] ] ] 5 => array:2 [ "identificador" => "sec0085" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0090" "titulo" => "Results" "secciones" => array:8 [ 0 => array:2 [ "identificador" => "sec0095" "titulo" => "Assessment of histopathological alterations" ] 1 => array:2 [ "identificador" => "sec0100" "titulo" => "Assessment of biochemical alterations" ] 2 => array:2 [ "identificador" => "sec0105" "titulo" => "Assessment of kidney function" ] 3 => array:2 [ "identificador" => "sec0110" "titulo" => "Assessment of oxidative stress" ] 4 => array:2 [ "identificador" => "sec0115" "titulo" => "Assessment of lactate dehydrogenase" ] 5 => array:2 [ "identificador" => "sec0120" "titulo" => "Assessment of inflammation markers" ] 6 => array:2 [ "identificador" => "sec0125" "titulo" => "Assessment of apoptosis" ] 7 => array:2 [ "identificador" => "sec0130" "titulo" => "Assessment of Ca ATPase and Na/K-ATPase enzyme activities" ] ] ] 7 => array:2 [ "identificador" => "sec0135" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0140" "titulo" => "Conclusion" ] 9 => array:2 [ "identificador" => "sec0145" "titulo" => "Conflict of interest" ] 10 => array:2 [ "identificador" => "sec0150" "titulo" => "Funding" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-07-16" "fechaAceptado" => "2018-10-23" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1163642" "palabras" => array:6 [ 0 => "Renal ischemia/reperfusion injury" 1 => "Berberine" 2 => "Histopathology" 3 => "Oxidative stress" 4 => "Apoptosis" 5 => "Inflammation" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1163641" "palabras" => array:6 [ 0 => "Insuficiencia renal por isquemia/reperfusión" 1 => "Berberina" 2 => "Histopatología" 3 => "Estrés oxidativo" 4 => "Apoptosis" 5 => "Inflamación" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "BackgroundIschemia–reperfusion injury causes various severe morphological and functional changes in diabetic patients. To date, numerous antidiabetic and antioxidant agents have been used for treatment of the disease-related changes. ObjectivesWe aimed to examine effective therapeutic doses or doses of berberine against renal ischemia/reperfusion injury (IRI) in a streptozotocin (STZ)-induced diabetic rat model by histopathological and biochemical analysis. MethodsThirty male Sprague Dawley rats were treated with STZ injection for the development of diabetes, and divided into the following groups: STZ-induced diabetic group (STZ); IRI-induced diabetic group (STZ+IRI); 50mg/kg berberine (BRB) treated diabetic group after inducing IRI (STZ+IRI+BRB1); 100mg/kg BRB treated diabetic group after IRI (STZ+IRI+BRB2); 150mg/kg BRB treated diabetic group after IRI (STZ+IRI+BRB3). Bilateral renal ischemia model was applied for 45min, then reperfusion was allowed for 14 days in STZ-induced diabetic rats. Renal injury was detected histopathologically. Blood urea nitrogen (BUN), creatinine and lactate dehydrogenase (LDH) levels were measured in serum using the ELISA method. Total antioxidant status (TAS) and total oxidant status (TOS) of renal tissue was studied by spectrophotometric assay. Oxidative stress index (OSI) was calculated as TOS-to-TAS ratio. Tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), Na+/K+-ATPase (sodium pump), and Ca2+-ATPase (calcium ATPase) enzyme levels were measured in tissues using the ELISA method. Anti-apoptotic Bax and pro-apoptotic Bcl-2 protein levels were detected by Western blot analysis. All data were evaluated statistically. ResultsThe highest histopathological score was detected in the STZ+IRI group compared to the other group. BRB administration at the doses of 100mg/kg and 150mg/kg markedly improved renal injury. BUN and creatinine levels significantly increased in the STZ+IRI group compared to the STZ group (p<0.001). 100mg/kg and 150mg/kg BRB administration significantly decreased those levels (p<0.01). The highest TOS and the lowest TAS levels were detected in the STZ+IRI group (p<0.001). IRI markedly aggravated inflammation via increasing levels of TNF-α and CRP (<0.001), and caused apoptosis via inducing Bcl-2 protein, and suppressing Bax protein (p<0.001). BRB administration at the doses of 100mg/kg and 150mg/kg showed anti-oxidant, anti-inflammatory and anti-apoptotic effects (p<0.01). The LDH enzyme, was used as a necrosis marker, was higher in the STZ+IRI group than other groups. BRB administration at all of the doses, resulted in the decline of LDH enzyme level (p<0.001). Ca2+-ATPase and Na+/K+-ATPase enzyme activities decreased in the STZ+IRI group compared to the STZ group (p<0.001), while BRB administration at the doses of 100mg/kg and 150mg/kg significantly increased those of enzyme activities, respectively (p<0.05). ConclusionIschemia with diabetes caused severe histopathological and biochemical damage in renal tissue. The high doses of berberine markedly improved histopathological findings, regulated kidney function via decreasing BUN and creatinine levels, and rearranged intercellular ion concentration via increasing Na+/K+-ATPase and Ca2+− ATPase levels. Berberine showed anti-oxidant, anti-apoptotic, and anti-inflammatory effects. According to these data, we suggest that berberine at the doses of 100 and 150mg may be used as a potential therapeutic agent to prevent renal ischemic injury." "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objectives" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "AntecedentesLa reperfusión de la isquemia provoca graves cambios morfológicos y funcionales en los pacientes diabéticos. Hasta la fecha numerosos antidiabéticos y agentes antioxidantes han sido utilizados para el tratamiento de los cambios relacionados con la enfermedad. ObjetivosEl objetivo fue examinar las dosis terapéuticas efectivas o las dosis de berberina (BRB) frente a la insuficiencia renal por isquemia/reperfusión (IRI) en estreptozotocina (STZ) inducida por el modelo de rata por análisis histopatológico y bioquímico. MétodosTreinta ratas machos Spraque-Dawley fueron tratadas con inyección de STZ para el desarrollo de diabetes, se dividieron en los siguientes grupos: grupo diabético inducido por STZ; grupo diabético inducido por IRI (STZ+IRI); grupo diabético tratado con 50mg/kg de BRB después de la inducción de IRI (STZ+IRI+BRB1); grupo diabético tratado con 100mg/kg de BRB después de IRI (STZ+IRI+BRB2), y grupo diabético tratado con 150mg/kg de BRB después de IRI (STZ+IRI+BRB3). Se aplicó un modelo de isquemia renal bilateral durante 45min, luego se permitió la reperfusión durante 14 días en ratas diabéticas inducidas por STZ. La lesión renal fue detectada histopatológicamente. Los niveles de nitrógeno ureico en sangre (BUN), creatinina y lactato deshidrogenasa (LDH) se midieron en suero por el método ELISA. El estado antioxidante total (TAS) y el estado oxidante total (TOS) del tejido renal se estudiaron mediante un ensayo espectrofotométrico. El índice de estrés oxidativo (OSI) fue calculado como la relación TOS-a-TAS. El factor de necrosis tumoral alfa (TNF-α), proteína C reactiva (CRP), Na+/K+-ATPasa (bomba de sodio) y la Ca2+-ATPasa (calcio ATPasa) de la enzima se midieron los niveles en los tejidos mediante el método ELISA. Los niveles de proteína anti-apoptótica Bax y pro-apoptótica Bcl-2 se detectaron por el análisis de Western blot. Todos los datos fueron evaluados estadísticamente. ResultadosLa mayor puntuación histopatológica fue detectada en el grupo STZ+IRI en comparación con el otro grupo. La administración de BRB en dosis de 100 y 150mg/kg mejoró notablemente la lesión renal. Los niveles de BUN y creatinina aumentaron significativamente en el grupo STZ+IRI en comparación con el grupo STZ (p<0,001). La administración de 100 y 150mg/kg de BRB disminuyó significativamente esos niveles (p<0,01). Los TOS más altos y los niveles más bajos de TAS se detectaron en el grupo STZ+IRI (p<0,001). El IRI agravó notablemente la inflamación a través del aumento de los niveles de TNF-alfa y de PCR (<0,001), y causó la apoptosis a través de la inducción de la proteína Bcl-2 y la supresión de la proteína Bax (p<0,001). La administración de BRB con las dosis de 100 y 150mg/kg mostró efectos antioxidante, antiinflamatorio y antiapoptóticos (p<0,01). La enzima LDH que se usó como marcador de necrosis fue mayor en el grupo STZ+IRI que en los otros grupos. La administración de BRB en todas las dosis, dio lugar a una disminución del nivel de la enzima LDH (p<0,001). Las actividades de las enzimas Ca2+-ATPasa y Na+/K+-ATPasa disminuyeron en el grupo STZ+IRI en comparación con el grupo STZ (p<0,001, mientras que la administración de BRB en dosis de 100 y 150mg/kg incrementó significativamente las actividades de las enzimas, respectivamente (p<0,05). ConclusiónLa isquemia con diabetes causó graves daños histopatológicos y bioquímicos en el tejido renal. Las altas dosis de BRB mejoraron notablemente los hallazgos histopatológicos, la función renal regulada a través de la disminución de los niveles de BUN y creatinina, y la concentración de iones intercelulares reordenados mediante el aumento de los niveles de Na+/K+-ATPasa y la Ca2+-ATPasa. La BRB mostró efectos antioxidantes, antiapoptóticos y antiinflamatorios. De acuerdo con estos datos, sugerimos que la BRB en dosis de 100 y 150mg se puede usar como un agente terapéutico potencial para prevenir la lesión isquémica renal." "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Antecedentes" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivos" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusión" ] ] ] ] "multimedia" => array:10 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 876 "Ancho" => 1740 "Tamanyo" => 679041 ] ] "descripcion" => array:1 [ "en" => "Light microscopic figures of renal cortex in STZ+IRI group. (a) Tubular dilatation, atrophy (asterisks), thyroidization (black arrows) and interstitial mononuclear cell infiltration (yellow arrowheads) are obvious. Hematoxylin & Eosin; 20×. (b) Tubular degeneration (dark blue arrowheads) is obvious. Basement membranes are not clearly seen, brush border loss is prominent. Periodic Acid Schiff; 20×. (c) Tubular necrosis (red arrowheads) and interstitial cell infiltration (yellow arrowheads) are clearly seen. Note that hemosiderin is accumulated within the area. Hematoxylin & Eosin; 10×. (d) Interstitial mononuclear cell infiltration (yellow arrowheads) and glomerular and tubular basement membrane thickening is observed. Periodic Acid Schiff; 40×. (e) Tubular degeneration (red arrowheads), interstitial cell infiltration, and fibrosis (yellow arrows) are seen. Masson's trichrome 20×. (f) Capillary dilatation and congestion are observed. Hematoxylin & Eosin; 20×." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1301 "Ancho" => 1733 "Tamanyo" => 864964 ] ] "descripcion" => array:1 [ "en" => "Histological sections of STZ+BRB1 (a and b), STZ+BRB2 (c), and STZ+BRB3 groups (d). Dose-dependent improvement on all of the histological alterations induced by diabetes (STZ) and ischemia reperfusion injury (IRI) is observed. (a) and (c) Hematoxylin & Eosin stain; (b) and (d) Periodic Acid Schiff stain; 20×)." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1838 "Ancho" => 1355 "Tamanyo" => 106781 ] ] "descripcion" => array:1 [ "en" => "Mean serum blood urea nitrogen (BUN) and creatinine levels in all groups. The data are expressed as mean±standard deviation (*p<0.05 vs. STZ+IRI group. One way ANOVA, post hoc Tukey test)." ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1713 "Ancho" => 2309 "Tamanyo" => 166475 ] ] "descripcion" => array:1 [ "en" => "Mean tissue total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) in all groups. The data are expressed as mean±standard deviation (*p<0.05 vs. STZ+IRI group. One way ANOVA, post hoc Tukey test)." ] ] 4 => array:7 [ "identificador" => "fig0025" "etiqueta" => "Fig. 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1462 "Ancho" => 2158 "Tamanyo" => 92947 ] ] "descripcion" => array:1 [ "en" => "Mean serum lactate dehydrogenase level in all groups. The data are expressed as mean±standard deviation (* p<0.05 vs. STZ+IRI group. One way ANOVA, post hoc Tukey test)." ] ] 5 => array:7 [ "identificador" => "fig0030" "etiqueta" => "Fig. 6" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr6.jpeg" "Alto" => 1823 "Ancho" => 1422 "Tamanyo" => 101980 ] ] "descripcion" => array:1 [ "en" => "Mean tumor necrosis factor alfa (TNF-α) and C-reactive protein (CRP) levels in all groups. The data are expressed as mean±standard deviation (*p<0.05 vs. STZ+IRI group. One way ANOVA, post hoc Tukey test)." ] ] 6 => array:7 [ "identificador" => "fig0035" "etiqueta" => "Fig. 7" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr7.jpeg" "Alto" => 890 "Ancho" => 1518 "Tamanyo" => 98441 ] ] "descripcion" => array:1 [ "en" => "Western blot analysis of Bax and Bcl 2 proteins and mean Bax and Bcl 2 levels in renal tissues of all groups. The data are expressed as mean±standard deviation (*p<0.05 vs. STZ+IRI group. One way ANOVA, post hoc Tukey test)." ] ] 7 => array:7 [ "identificador" => "fig0040" "etiqueta" => "Fig. 8" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr8.jpeg" "Alto" => 875 "Ancho" => 2123 "Tamanyo" => 107112 ] ] "descripcion" => array:1 [ "en" => "Mean calcium triphosphatase (Ca2+-ATPase) and sodium potassium adenosine triphosphatase (Na+/K+-ATPase) enzyme activities in all groups. The data are expressed as mean±standard deviation (*p<0.05 vs. STZ+IRI group. One way ANOVA, post hoc Tukey test)." ] ] 8 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "The data are expressed median, minimum and maximum using non-parametric Kruskal–Wallis test. p value<0.05 was considered significant. All results belong to STZ+IRI compared to the other groups, and p values were represented in the columns." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Left kidney \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Pathological alterations \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">STZ (n=6)</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">STZ+IRI (n=6)</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">STZ+IRI+BRB1 (n=6)</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">STZ+IRI+BRB2 (n=6)</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">STZ+IRI+BRB3 (n=6)</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Minimum to maximum (median) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p value \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Minimum to maximum (median) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p value \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Minimum to maximum (median) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p value \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Minimum to maximum (median) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p value \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Minimum to maximum (median) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Proximal tubular damage</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Proximal tubular dilation and atrophy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1–2 (1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.007 (U=2.00) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2–3 (3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1–3 (2.50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>0.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1–2 (1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.004 (U=1.00) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–2 (1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.004 (U=1.00) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Loss of brush border \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–1 (1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.003 (U=0.00) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2–4 (3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1–2 (1.50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.011 (U=3.00) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–1 (0.50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.003 (U=0.00) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–1 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.003 (U=0.00) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Proximal tubular necrosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–2 (1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.004 (U=0.50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2–4 (3.50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1–3 (2.50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>0.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1–2 (2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.007 (U=2.00) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–2 (1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.004 (U=0.50) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="12" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Distal tubular damage</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Distal tubular dilation and atrophy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1–2 (1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.008 (U=2.00) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2–4 (3.50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1–4 (2.50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>0.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1–2 (1.50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.012 (U=3.00) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1–2 (1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.004 (U=1.00) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Distal tubular necrosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–2 (1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.005 (U=1.00) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2–4 (3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1–3 (2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>0.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1–3 (2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>0.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1–2 (1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.008 (U=2.00) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="12" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Glomerular damage \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Glomerular basement membrane thickening \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–1 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.027 (U=5.00) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–2 (2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–2 (1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>0.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–1 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.014 (U=4.00) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–1 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.014 (U=4.00) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="12" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Tubulointerstital damage</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Interstitial fibrosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–1 (0.50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>0.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–1 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–2 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>0.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–1 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>0.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–3 (0.50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>0.05 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hemorrhage \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–3 (1.50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.005 (U=1.00) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3–4 (4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–4 (2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.029 (U=5.00) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–1 (1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.003 (U=0.00) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–2 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.003 (U=0.00) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mononuclear cell infiltration \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–2 (1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.008 (U=2.00) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2–4 (3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1–3 (2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.008 (U=2.00) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–2 (0.50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.006 (U=1.00) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–1 (0.50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.003 (U=2.00) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="12" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Vascular damage \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Glomerulointerstitial congestion \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–3 (2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.020 (U=4.00) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2–4 (3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–3 (1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.014 (U=3.00) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–2 (1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.004 (U=0.50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–1 (1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.003 (U=0.00) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="12" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Total damage \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4–17 (10) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.004 (U=0.00) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25–28 (27) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10–26 (15.50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.009 (U=2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6–11 (10) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.004 (U=0.00) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3–10 (8.50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.004 (U=0.00) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2148166.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Summary statistics and Mann Whitney U test results about histopathological scores in the all groups." ] ] 9 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "The data are expressed as mean±standard deviation. p value<0.05 was considered significant. All results belong to STZ+IRI compared to the other groups, and p values were represented in the columns." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Biochemical parameters \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">STZ (n=6)</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">STZ+IRI (n=6)</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">STZ+IRI+BRB1 (n=6)</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">STZ+IRI+BRB2 (n=6)</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">STZ+IRI+BRB3 (n=6)</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mean±SD \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p value \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mean±SD \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p value \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mean±SD \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p value \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mean±SD \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p value \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mean±SD \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Blood urea nitrogen (BUN) (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37.19±2.79 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">120.32±0.98 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">114.29±1.55 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.002 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">95.37±3.76 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">88.96±1.95 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Creatinine (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.98±0.08 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.31±0.17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.17±0.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>0.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.68±0.17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.00±0.09 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Total antioxidant capacity (TAS) (mmol Trolox equiv./l) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.84±0.06 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.21±0.04 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.36±0.06 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.55±0.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.73±0.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Total oxidant status (TOS) (μmol H2O2 Trolox equiv./l) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10.83±0.22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13.08±0.35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11.18±0.32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11.39±0.34 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12.17±0.24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Oxidative stress index (OSI=TOS/TAS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.93±0.09 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10.86±0.48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.25±0.47 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.36±0.31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.05±0.12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Tumor necrosis factor alpha (TNF-α) (pg/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">638.98±16.82 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1108.38±46.02 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1011.43±46.28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.008 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">918.44±19.62 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">895.96±68.23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">C-reactive protein (CRP) (ng/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.28±0.04 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9.93±1.29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.14±0.13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.34±0.23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.91±0.10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lactate dehydrogenase (LDH) (mU/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10.99±0.36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24.28±0.38 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22.14±0.97 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19.98±0.24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17.40±0.87 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Calcium triphosphatase (Ca2+-ATPase) (ng/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12.22±0.79 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10.22±0.56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9.49±0.98 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>0.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10.46±0.42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>0.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12.35±0.52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sodium potassium adenosine triphosphatase (Na+/K+-ATPase) (ng/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13.38±1.21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10.94±0.47 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10.60±0.31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>0.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12.29±0.71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.039 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11.10±0.66 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>0.05 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Bax \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.48±0.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.76±0.17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.54±0.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.009 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.15±0.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.08±0.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Bcl-2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.18±0.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.39±0.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.42±0.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>0.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.10±0.02 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.92±0.03 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2148167.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Summary statistics and One-way ANOVA test (post hoc Tukey HSD) results about biochemical analysis in the all groups." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:50 [ 0 => array:3 [ "identificador" => "bib0255" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatic ischemia/reperfusion injury associates with acute kidney injury in liver transplantation: prospective cohort study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "I. Jochmans" 1 => "N. Meurisse" 2 => "A. Neyrinck" 3 => "M. Verhaegen" 4 => "D. Monbaliu" 5 => "J. Pirenne" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/lt.24728" "Revista" => array:6 [ "tituloSerie" => "Liver Transpl" "fecha" => "2017" "volumen" => "23" "paginaInicial" => "634" "paginaFinal" => "644" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28124458" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0260" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ischemia/reperfusion injury following acute myocardial infarction: a critical issue for clinicians and forensic pathologists" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M. Neri" 1 => "I. Riezzo" 2 => "N. Pascale" 3 => "C. Pomara" 4 => "E. Turillazzi" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Mediators Inflamm" "fecha" => "2017" "volumen" => "2017" "paginaInicial" => "1" "paginaFinal" => "14" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0265" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Current mechanistic concepts in ischemia and reperfusion injury" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.Y. Wu" 1 => "G.T. Yiang" 2 => "W.T. Liao" 3 => "A.P. Tsai" 4 => "Y.L. Cheng" 5 => "P.W. Cheng" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1159/000489241" "Revista" => array:6 [ "tituloSerie" => "Cell Physiol Biochem" "fecha" => "2018" "volumen" => "46" "paginaInicial" => "1650" "paginaFinal" => "1667" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29694958" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0270" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal ischemia/reperfusion injury in diabetic rats: the role of local ischemic preconditioning" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Ozbilgin" 1 => "S. Ozkardesler" 2 => "M. Akan" 3 => "N. Boztas" 4 => "M. Ozbilgin" 5 => "B.U. Ergur" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Biomed Res Int" "fecha" => "2016" "volumen" => "2016" "paginaInicial" => "1" "paginaFinal" => "9" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0275" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Thymoquinone improves the kidney and liver changes induced by chronic cyclosporine A treatment and acute renal ischaemia/reperfusion in rats" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M.M. Farag" 1 => "G.O. Ahmed" 2 => "R.R. Shehata" 3 => "A.H. Kazem" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/jphp.12363" "Revista" => array:6 [ "tituloSerie" => "J Pharm Pharmacol" "fecha" => "2015" "volumen" => "67" "paginaInicial" => "731" "paginaFinal" => "739" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25644194" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0280" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ischemia causes rapidly progressive nephropathy in the diabetic rat" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "J. Melin" 1 => "O. Hellberg" 2 => "L.M. Akyurek" 3 => "O. Kallskog" 4 => "E. Larsson" 5 => "B.C. Fellström" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ki.1997.420" "Revista" => array:6 [ "tituloSerie" => "Kidney Int" "fecha" => "1997" "volumen" => "52" "paginaInicial" => "985" "paginaFinal" => "991" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9328937" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0285" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal ischemia/reperfusion injury; from pathophysiology to treatment" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M. Malek" 1 => "M. Nematbakhsh" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.12861/jrip.2015.06" "Revista" => array:6 [ "tituloSerie" => "J Renal Inj Prev" "fecha" => "2015" "volumen" => "4" "paginaInicial" => "20" "paginaFinal" => "27" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26060833" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0290" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Delayed recovery of renal regional blood flow in diabetic mice" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "H. Shi" 1 => "D. Patschan" 2 => "T. Epstein" 3 => "M.S. Goligorsky" 4 => "J. Winaver" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1152/ajprenal.00215.2007" "Revista" => array:6 [ "tituloSerie" => "Am J Physiol Renal Physiol" "fecha" => "2007" "volumen" => "293" "paginaInicial" => "F1512" "paginaFinal" => "F1517" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17881464" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0295" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Acute renal failure in patients with type 1 diabetes mellitus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "G. Woodrow" 1 => "A.M. Brownjohn" 2 => "J.H. Turney" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/pgmj.70.821.192" "Revista" => array:6 [ "tituloSerie" => "Postgrad Med J" "fecha" => "1994" "volumen" => "70" "paginaInicial" => "192" "paginaFinal" => "194" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8183751" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0300" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hyperglycaemia and renal ischaemia–reperfusion injury" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J. Melin" 1 => "O. Hellberg" 2 => "B. Fellström" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/ndt/18.3.460" "Revista" => array:6 [ "tituloSerie" => "Nephrol Dial Transplant" "fecha" => "2003" "volumen" => "18" "paginaInicial" => "460" "paginaFinal" => "462" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12584261" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0305" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The effects of Berberis vulgaris fruit extract on serum lipoproteins, apoB, apoA-I, homocysteine, glycemic control and total antioxidant capacity in type 2 diabetic patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "F. Shidfar" 1 => "S.S. Ebrahimi" 2 => "S. Hosseini" 3 => "I. Heydari" 4 => "S. Shidfar" 5 => "G. Hajhassani" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Iran J Pharm Res" "fecha" => "2012" "volumen" => "11" "paginaInicial" => "643" "paginaFinal" => "652" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24250489" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0310" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Berberine improves mesenteric artery insulin sensitivity through up-regulating insulin receptor-mediated signaling in diabetic rats" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F.H. Geng" 1 => "G.H. Li" 2 => "X. Zhang" 3 => "P. Zhang" 4 => "M.Q. Dong" 5 => "Z.J. Zhao" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/bph.13466" "Revista" => array:6 [ "tituloSerie" => "Br J Pharmacol" "fecha" => "2016" "volumen" => "173" "paginaInicial" => "1569" "paginaFinal" => "1579" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26914282" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0315" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Antioxidant and anti-inflammatory activities of berberine in the treatment of diabetes mellitus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Z. Li" 1 => "Y.N. Geng" 2 => "J.D. Jiang" 3 => "W.J. Kong" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1155/2014/289264" "Revista" => array:5 [ "tituloSerie" => "Evid Based Complement Alternat Med" "fecha" => "2014" "volumen" => "2014" "paginaInicial" => "289264" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24669227" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0320" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Berberine inhibits enterovirus 71 replication by downregulating the MEK/ERK signaling pathway autophagy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H. Wang" 1 => "K. Li" 2 => "L. Ma" 3 => "S. Wu" 4 => "J. Hu" 5 => "H. Yan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/1743-422X-4-1" "Revista" => array:6 [ "tituloSerie" => "Virol J" "fecha" => "2017" "volumen" => "4" "paginaInicial" => "1" "paginaFinal" => "8" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17204159" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0325" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inhibition of oral streptococci growth induced by the complementary action of berberine chloride and antibacterial compounds" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A. Dziedzic" 1 => "R.D. Wojtyczka" 2 => "R. Kubina" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Molecules" "fecha" => "2015" "volumen" => "20" "paginaInicial" => "13705" "paginaFinal" => "13724" ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0330" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Neuroprotective effect of ischemic preconditioning via modulating the expression of cerebral miRNAs against transient cerebral ischemia in diabetic rats" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "O. Altintas" 1 => "M.O. Altintas" 2 => "M. Kumas" 3 => "T. Asil" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1080/01616412.2016.1232013" "Revista" => array:6 [ "tituloSerie" => "Neurol Res" "fecha" => "2016" "volumen" => "38" "paginaInicial" => "1003" "paginaFinal" => "1011" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27635859" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0335" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Protective role of recombinant human erythropoietin in kidney and lung injury following renal bilateral ischemia–reperfusion in rat model" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Moeini" 1 => "M. Nematbakhsh" 2 => "M. Fazilati" 3 => "A. Talebi" 4 => "A.A. Pilehvarian" 5 => "F. Azarkish" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Int J Prev Med" "fecha" => "2013" "volumen" => "4" "paginaInicial" => "648" "paginaFinal" => "655" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23930182" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0340" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A new automated colorimetric method for measuring total oxidant status" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "O. Erel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.clinbiochem.2005.08.008" "Revista" => array:6 [ "tituloSerie" => "Clin Biochem" "fecha" => "2005" "volumen" => "38" "paginaInicial" => "1103" "paginaFinal" => "1111" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16214125" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0345" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Analysis of the diagnostic efficiency of serum oxidative stress parameters in patients with breast cancer at various clinical stages" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.F. Feng" 1 => "L. Lu" 2 => "C.M. Dai" 3 => "D. Wang" 4 => "Y.H. Yang" 5 => "Y.W. Yang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.clinbiochem.2016.02.005" "Revista" => array:6 [ "tituloSerie" => "Clin Biochem" "fecha" => "2016" "volumen" => "49" "paginaInicial" => "692" "paginaFinal" => "698" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26899366" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0350" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "O. Erel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.clinbiochem.2003.11.015" "Revista" => array:6 [ "tituloSerie" => "Clin Biochem" "fecha" => "2004" "volumen" => "37" "paginaInicial" => "277" "paginaFinal" => "285" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15003729" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0355" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The Madrid Acute Renal Failure Group. Epidemiology of acute renal failure: a prospective multicenter community based study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "F. Liaño" 1 => "J. Pascual" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ki.1996.380" "Revista" => array:6 [ "tituloSerie" => "Kidney Int" "fecha" => "1996" "volumen" => "50" "paginaInicial" => "811" "paginaFinal" => "818" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8872955" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0360" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inflammatory cells in ischemic acute renal failure" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J.J. Friedewald" 1 => "H. Rabb" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1523-1755.2004.761_3.x" "Revista" => array:6 [ "tituloSerie" => "Kidney Int" "fecha" => "2004" "volumen" => "66" "paginaInicial" => "486" "paginaFinal" => "490" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15253694" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0365" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Animal models of kidney inflammation in translational medicine" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A. Holderied" 1 => "N.H. Andersen" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Drug Discov Today Dis Model" "fecha" => "2014" "volumen" => "11" "paginaInicial" => "19" "paginaFinal" => "27" ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0370" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ischemic acute renal failure: an inflammatory disease?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J.V. Bonventre" 1 => "A. Zuk" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1523-1755.2004.761_2.x" "Revista" => array:6 [ "tituloSerie" => "Kidney Int" "fecha" => "2004" "volumen" => "66" "paginaInicial" => "480" "paginaFinal" => "485" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15253693" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0375" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cellular pathophysiology of ischemic acute kidney injury" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J.V. Bonventre" 1 => "L. Yang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1172/JCI45161" "Revista" => array:6 [ "tituloSerie" => "J Clin Invest" "fecha" => "2011" "volumen" => "121" "paginaInicial" => "4210" "paginaFinal" => "4221" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22045571" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0380" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Treatment of acute renal failure" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "R.A. Star" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1046/j.1523-1755.1998.00210.x" "Revista" => array:6 [ "tituloSerie" => "Kidney Int" "fecha" => "1998" "volumen" => "54" "paginaInicial" => "1817" "paginaFinal" => "1831" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9853246" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0385" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal ischemia/reperfusion injury: functional tissue preservation by anti-activated 1 integrin therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Molina" 1 => "M. Ubeda" 2 => "M.M. Escribese" 3 => "L. García-Bermejo" 4 => "D. Sancho" 5 => "G. Pérez de Lema" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1681/ASN.2004070528" "Revista" => array:6 [ "tituloSerie" => "J Am Soc Nephrol" "fecha" => "2005" "volumen" => "16" "paginaInicial" => "374" "paginaFinal" => "382" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15590758" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0390" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renoprotective effect of berberine via intonation on apoptosis and mitochondrial-dependent pathway in renal ischemia reperfusion-induced mutilation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A. Visnagri" 1 => "A.D. Kandhare" 2 => "S.L. Bodhankar" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Ren Fail" "fecha" => "2015" "volumen" => "7" "paginaInicial" => "482" "paginaFinal" => "493" ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0395" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lycopene has reduced renal damage histopathologically and biochemically in experimental renal ischemia–reperfusion injury" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Kaya" 1 => "R. Karabulut" 2 => "Z. Turkyilmaz" 3 => "K. Sonmez" 4 => "G. Kulduk" 5 => "Ö. Gülbahar" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3109/0886022X.2015.1064742" "Revista" => array:6 [ "tituloSerie" => "Ren Fail" "fecha" => "2015" "volumen" => "37" "paginaInicial" => "1390" "paginaFinal" => "1395" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26161692" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0400" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hyperglycemia increases susceptibility to ischemic necrosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "D. Lévigne" 1 => "M. Tobalem" 2 => "A. Modarressi" 3 => "B. Pittet-Cuénod" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Biomed Res Int" "fecha" => "2013" "volumen" => "2013" "paginaInicial" => "1" "paginaFinal" => "5" ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0405" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Neuroprotective effect of ischemic preconditioning via modulating the expression of adropin and oxidative markers against transient cerebral ischemia in diabetic rats" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "O. Altintas" 1 => "M. Kumas" 2 => "M.O. Altintas" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.peptides.2016.03.011" "Revista" => array:6 [ "tituloSerie" => "Peptides" "fecha" => "2016" "volumen" => "79" "paginaInicial" => "31" "paginaFinal" => "38" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27020247" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0410" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vascularization pattern after ischemic stroke is different in control versus diabetic rats: relevance to stroke recovery" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "R. Prakash" 1 => "W. Li" 2 => "Z. Qu" 3 => "M.A. Johnson" 4 => "S.C. Fagan" 5 => "A. Ergul" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/STROKEAHA.113.001660" "Revista" => array:6 [ "tituloSerie" => "Stroke" "fecha" => "2013" "volumen" => "44" "paginaInicial" => "2875" "paginaFinal" => "2882" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23920018" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0415" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Antioxidant capacity after acute ischaemic stroke" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "S.E. Gariballa" 1 => "T.P. Hutchin" 2 => "A.J. Sinclair" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/qjmed/95.10.685" "Revista" => array:6 [ "tituloSerie" => "QJM" "fecha" => "2002" "volumen" => "95" "paginaInicial" => "685" "paginaFinal" => "690" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12324641" "web" => "Medline" ] ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0420" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Glomerular and proximal tubular morphology after single nephron obstruction" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "G.A. Tanner" 1 => "A.P. Evan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ki.1989.300" "Revista" => array:6 [ "tituloSerie" => "Kidney Int" "fecha" => "1989" "volumen" => "36" "paginaInicial" => "1050" "paginaFinal" => "1060" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2601255" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0425" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Update on Mechanisms of ischemic acute kidney injury" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "P. Devarajan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1681/ASN.2006010017" "Revista" => array:6 [ "tituloSerie" => "J Am Soc Nephrol" "fecha" => "2006" "volumen" => "17" "paginaInicial" => "1503" "paginaFinal" => "1520" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16707563" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0430" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Detection of necrosis by release of lactate dehydrogenase activity" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "F.K. Chan" 1 => "K. Moriwaki" 2 => "M.J. De Rosa" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/978-1-62703-290-2_7" "Revista" => array:6 [ "tituloSerie" => "Methods Mol Biol" "fecha" => "2013" "volumen" => "979" "paginaInicial" => "65" "paginaFinal" => "70" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23397389" "web" => "Medline" ] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0435" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal cortical lactate dehydrogenase: a useful, accurate, quantitative marker of in vivo tubular injury and acute renal failure" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "R.A. Zager" 1 => "A.C. Johnson" 2 => "K. Becker" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "PLoS One" "fecha" => "2013" "volumen" => "8" "paginaInicial" => "1" "paginaFinal" => "8" ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0440" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Modulation of C-reactive protein, tumor necrosis factor-alpha, and adiponectin by diet, exercise, and weight loss" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M.J. Puglisi" 1 => "M.L. Fernandez" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3945/jn.108.097188" "Revista" => array:6 [ "tituloSerie" => "J Nutr" "fecha" => "2008" "volumen" => "138" "paginaInicial" => "2293" "paginaFinal" => "2296" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19022947" "web" => "Medline" ] ] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0445" "etiqueta" => "39" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tumor necrosis factor (TNF-alpha) and C-reactive protein (CRP) are positively associated with the risk of chronic kidney disease in patients with type 2 diabetes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "E.S. Yeo" 1 => "J.Y. Hwang" 2 => "J.E. Park" 3 => "Y.J. Choi" 4 => "K.B. Huh" 5 => "W.Y. Kim" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3349/ymj.2010.51.4.519" "Revista" => array:6 [ "tituloSerie" => "Yonsei Med J" "fecha" => "2010" "volumen" => "51" "paginaInicial" => "519" "paginaFinal" => "525" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20499416" "web" => "Medline" ] ] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0450" "etiqueta" => "40" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Berberine improves glucose homeostasis in streptozotocin-induced diabetic rats in association with multiple factors of insulin resistance" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Y. Chen" 1 => "Y. Wang" 2 => "J. Zhang" 3 => "C. Sun" 4 => "A. Lopez" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "ISRN Endocrinol" "fecha" => "2011" "volumen" => "2011" "paginaInicial" => "1" "paginaFinal" => "8" ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib0455" "etiqueta" => "41" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Berberine reduces the expression of adipogenic enzymes and inflammatory molecules of 3T3-L1 adipocyte" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B.H. Choi" 1 => "I.S. Ahn" 2 => "Y.H. Kim" 3 => "J.W. Park" 4 => "S.Y. Lee" 5 => "C.K. Hyun" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/emm.2006.71" "Revista" => array:6 [ "tituloSerie" => "Exp Mol Med" "fecha" => "2006" "volumen" => "38" "paginaInicial" => "599" "paginaFinal" => "605" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17202835" "web" => "Medline" ] ] ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib0460" "etiqueta" => "42" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Protective effect of ischemic preconditioning on myocardium against remote tissue injury following transient focal cerebral ischemia in diabetic rats" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M. Kumas" 1 => "O. Altintas" 2 => "E. Karatas" 3 => "A. Kocyigit" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.5935/abc.20170164" "Revista" => array:7 [ "tituloSerie" => "Arq Bras Cardiol" "fecha" => "2017" "volumen" => "109" "paginaInicial" => "516" "paginaFinal" => "526" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29160389" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0195670117301354" "estado" => "S300" "issn" => "01956701" ] ] ] ] ] ] ] 42 => array:3 [ "identificador" => "bib0465" "etiqueta" => "43" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hypoxia leads to Na, K-ATPase downregulation via Ca2+ release-activated Ca2+ channels and AMPK activation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G.A. Gusarova" 1 => "H.E. Trejo" 2 => "L.A. Dada" 3 => "A. Briva" 4 => "L.C. Welch" 5 => "R.B. Hamanaka" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/MCB.05114-11" "Revista" => array:6 [ "tituloSerie" => "Mol Cell Biol" "fecha" => "2011" "volumen" => "31" "paginaInicial" => "3546" "paginaFinal" => "3556" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21730292" "web" => "Medline" ] ] ] ] ] ] ] ] 43 => array:3 [ "identificador" => "bib0470" "etiqueta" => "44" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Plasma membrane and sarcoplasmic reticulum Ca-ATPase and smooth muscle" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J.M. Gonzalez" 1 => "L.J. Jost" 2 => "D. Rouse" 3 => "W.N. Suki" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Miner Electrolyte Metab" "fecha" => "1996" "volumen" => "22" "paginaInicial" => "345" "paginaFinal" => "348" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8933505" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0140673610614584" "estado" => "S300" "issn" => "01406736" ] ] ] ] ] ] ] 44 => array:3 [ "identificador" => "bib0475" "etiqueta" => "45" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Evidence that BCL-2 represses apoptosis by regulating endoplasmic reticulum-associated Ca2+ fluxes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M. Lam" 1 => "G. Dubyak" 2 => "L. Chen" 3 => "G. Nuñez" 4 => "R.L. Miesfeld" 5 => "C.W. Distelhorst" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1073/pnas.91.14.6569" "Revista" => array:6 [ "tituloSerie" => "Proc Natl Acad Sci USA" "fecha" => "1994" "volumen" => "91" "paginaInicial" => "6569" "paginaFinal" => "6573" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8022822" "web" => "Medline" ] ] ] ] ] ] ] ] 45 => array:3 [ "identificador" => "bib0480" "etiqueta" => "46" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The Na,K-ATPase" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J.C. Skou" 1 => "M. Esmann" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/bf00768846" "Revista" => array:6 [ "tituloSerie" => "J. Bioenerg Biomembr" "fecha" => "1992" "volumen" => "24" "paginaInicial" => "249" "paginaFinal" => "261" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1328174" "web" => "Medline" ] ] ] ] ] ] ] ] 46 => array:3 [ "identificador" => "bib0485" "etiqueta" => "47" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Down-regulated Na(+)/K(+)-ATPase activity in ischemic penumbra after focal cerebral ischemia/reperfusion in rats" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H. Huang" 1 => "Y.M. Chen" 2 => "F. Zhu" 3 => "S.T. Tang" 4 => "J.D. Xiao" 5 => "L.L. Li" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Int J Clin Exp Pathol" "fecha" => "2015" "volumen" => "8" "paginaInicial" => "12708" "paginaFinal" => "12717" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26722460" "web" => "Medline" ] ] ] ] ] ] ] ] 47 => array:3 [ "identificador" => "bib0490" "etiqueta" => "48" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Modulation of cardiac Na+,K+-ATPase cell surface abundance by simulated ischemia–reperfusion and ouabain preconditioning" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A. Belliard" 1 => "Y. Sottejeau" 2 => "Q. Duan" 3 => "J.L. Karabin" 4 => "S.V. Pierre" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1152/ajpheart.00374.2012" "Revista" => array:6 [ "tituloSerie" => "Am J Physiol Heart Circ Physiol" "fecha" => "2013" "volumen" => "304" "paginaInicial" => "H94" "paginaFinal" => "H103" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23086991" "web" => "Medline" ] ] ] ] ] ] ] ] 48 => array:3 [ "identificador" => "bib0495" "etiqueta" => "49" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Folic acid can contribute to memory deficit and Na+, K+-ATPase failure in the hippocampus of adolescent rats submitted to hypoxia-ischemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.V. Carletti" 1 => "B.F. Deniz" 2 => "J.J. Rojas" 3 => "P.M. Miguel" 4 => "J. Kolling" 5 => "E.B. Scherer" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "CNS Neurol Disord Drug Targets" "fecha" => "2016" "volumen" => "15" "paginaInicial" => "64" "paginaFinal" => "72" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26553162" "web" => "Medline" ] ] ] ] ] ] ] ] 49 => array:3 [ "identificador" => "bib0500" "etiqueta" => "50" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of FDP and Danshen on renal cortical Na-K-ATPase activity in rats after treatment with renal ischemia and gentamicin" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "F.M. Lu" 1 => "S.Y. Lin" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Chin Med J" "fecha" => "1989" "volumen" => "102" "paginaInicial" => "516" "paginaFinal" => "523" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2560955" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/02116995/0000003900000004/v3_201910190657/S0211699519300049/v3_201910190657/en/main.assets" "Apartado" => array:4 [ "identificador" => "42448" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Originales" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/02116995/0000003900000004/v3_201910190657/S0211699519300049/v3_201910190657/en/main.pdf?idApp=UINPBA000064&text.app=https://revistanefrologia.com/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0211699519300049?idApp=UINPBA000064"]

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Investigación de los efectos dependientes de dosis de la berberina contra la lesión de isquemia/reperfusión renal en ratas diabéticas experimentales

Meltem Kumaşa,

Autor para correspondencia

kumasmeltem@gmail.com

Corresponding author.

, Mukaddes Eşrefoğlua, Ersin Karataşb, Nurcihan Duymaçc, Songül Kanbayc, Ilyas Samet Ergünc, Mehmet Üyüklüd, Abdurrahim Koçyiğite

a Department of Histology and Embryology, Faculty of Medicine, Bezmialem Vakif University, 34093 Istanbul, Turkey

b Department of Molecular Biology and Genetics, Gebze Technical University, Kocaeli, Turkey

c Department of Pathology Laboratory Techniques, Vocational School of Health Services, Bezmialem Vakif University, 34093 Istanbul, Turkey

d Department of Physiology, Faculty of Medicine, Bezmialem Vakif University, 34093 Istanbul, Turkey

e Department of Medical Biochemistry, Faculty of Medicine, Bezmialem Vakif University, 34093 Istanbul, Turkey

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common chronic metabolic disorder&#44; is a serious risk factor for ischemic acute renal failure&#46; IRI accompanying by diabetes adversely affects development of severe diabetic nephropathy&#46;<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">8&#8211;10</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Berberine &#40;BRB&#41; which is the major active component of <span class="elsevierStyleItalic">Rhizoma Coptidis</span>&#44; has been widely used in Chinese for traditional treatment for diabetes&#46; BRB decreases elevated blood glucose level&#44; and improves insulin sensitivity in diabetic patients and also experimental diabetic animals&#46;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">11&#44;12</span></a> BRB also has an antioxidant activity against oxidative stress&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">13</span></a> Recently&#44; it has been reported that BRB possesses some additional effects such as anti-inflammatory&#44; 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Cambridge&#44; United Kingdom&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Study design</span><span id="sec0155" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Animals</span><p id="par0040" class="elsevierStylePara elsevierViewall">Animals were allowed free access to food and water at controlled room temperature &#40;22&#8211;25<span class="elsevierStyleHsp" style=""></span>&#176;C&#41; under a 12&#58;12-h day&#47;night cycle for the duration of the study&#46; All procedures were approved by the Animal Care and Use Committee at Bezmialem Vakif University and performed in accordance with institutional guidelines&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Thirty male Spraque Dawley rats &#40;Experimental Animal Research Laboratory at Bezmialem Vakif University&#44; Istanbul&#44; Turkey&#41; were divided into five groups as follows&#58; 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<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#41;&#59; STZ-induced diabetes<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>renal ischemia&#47;reperfusion<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>100<span class="elsevierStyleHsp" style=""></span>mg&#47;kg berberine treatment group 100<span class="elsevierStyleHsp" style=""></span>mg&#47;kg berberine treatment group &#40;STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">2</span>&#44; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#41;&#59; STZ-induced diabetes<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>renal ischemia&#47;reperfusion<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>150<span class="elsevierStyleHsp" style=""></span>mg&#47;kg berberine treatment group &#40;STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">3</span>&#44; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#41;&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Diabetes induction</span><p id="par0050" class="elsevierStylePara elsevierViewall">Experimental diabetes mellitus was induced by a single intraperitoneal injection of STZ at the dose of 50<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#46; It was prepared in 0&#46;1<span class="elsevierStyleHsp" style=""></span>mol&#47;l citrate buffer &#40;pH 4&#46;5&#41;&#44; immediately before use&#46; The blood samples at the 24th hour after STZ injection were obtained from the caudal veins&#46; Rats with a glucose concentration higher than 300<span class="elsevierStyleHsp" style=""></span>mg&#47;dL were considered as diabetic&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">16</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Renal ischemia&#47;reperfusion procedure</span><p id="par0055" class="elsevierStylePara elsevierViewall">Bilateral renal ischemia model was performed on diabetic rats&#46; Animals were anesthetized with intraperitoneal ketamine &#40;4<span class="elsevierStyleHsp" style=""></span>mg&#47;100<span class="elsevierStyleHsp" style=""></span>g&#41; and xylazine &#40;1&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;100<span class="elsevierStyleHsp" style=""></span>g&#41; before the onset of the surgery&#46; All animals were shaved and sterilized&#46; Both left and right kidneys were exposed by lateral incisions&#46; Then&#44; left and right renal arteries and veins were isolated&#46; Renal ischemia was achieved by clamping by left and right renal arteries with vascular clips for 45<span class="elsevierStyleHsp" style=""></span>min&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">17</span></a> At the end of this time&#44; vascular clips were removed&#44; and reperfusion was allowed&#46; Finally&#44; incisions were closed with surgical suture&#46; During the surgical procedure&#44; body temperature was monitored using a Nimomed&#174; infrared thermometer&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Berberine administration</span><p id="par0060" class="elsevierStylePara elsevierViewall">Berberine was freshly prepared every day by dissolving in distilled water&#46; The different doses &#40;50<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#44; 100<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#44; and 150<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#41; of berberine were administrated by oral gavage after inducing renal ischemia&#47;reperfusion &#40;IRI&#41;&#46; Initial berberine doses were applied at 24th hour after IRI&#44; and daily administrations were made for 14 days&#46; All experimental animals were sacrificed at 24th hour after the all doses were over&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Histological analysis</span><p id="par0065" class="elsevierStylePara elsevierViewall">Each kidney sample was divided into two equal pieces&#46; One piece was used for histological analyses&#44; the other was used for biochemical analyses&#46; For histological analysis&#44; tissues were fixed in 10&#37; formalin solution and after dehydration&#44; embedded in paraffin&#46; Five-micrometer &#40;&#956;m&#41; sections obtained from paraffin blocks were stained with Harris Hematoxylin &#40;Bio-optica Catalog no&#46; 05-06004&#47;L&#44; Milano&#44; Italy&#41; and Shandon Eosin Y Alcoholic &#40;Thermo scientific&#44; Catalog no&#46; 6766007&#44; Kalamazoo&#44; MI&#44; USA&#41;&#44; Masson Trichrome &#40;Bio-optica Catalog no&#46; 04-010802&#44; Milano&#44; Italy&#41;&#44; and Periodic Acid Schiff stains &#40;Beslab BS-0040&#44; Turkey&#41;&#46; Hematoxylin &#38; Eosin &#40;H&#38;E&#41; staining technique was used for the detection of pathological alterations including proximal&#47;distal tubular atrophy and necrosis&#44; congestion&#44; and infiltration&#46; Masson&#39;s trichrome staining technique was used for detecting&#44; and determining the degree of the fibrosis&#46; Periodic Acid Schiff staining technique was used for detecting of the status of the brush border and glomerular basement membrane&#46;</p><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Scoring system for evaluation of the kidney injury</span><p id="par0070" class="elsevierStylePara elsevierViewall">Total kidney injury for each sample was investigated by monitoring proximal tubular damage &#40;proximal tubular dilation and atrophy&#44; loss of brush border&#44; proximal tubular necrosis&#41;&#44; distal tubular damage &#40;distal tubular dilation&#47;atrophy and distal tubular necrosis&#41;&#44; glomerular damage &#40;glomerular basement membrane thickening&#41;&#44; interstitial damage &#40;interstitial fibrosis&#44; hemorrhage&#44; and mononuclear cell filtration&#41; and vascular damage &#40;interstitial congestion&#41;&#46; All findings were evaluated and scored as follows&#58; 0<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>absent &#40;&#60;10&#37;&#41;&#44; 1<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>minimal &#40;10&#8211;25&#37;&#41;&#44; 2<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>mild &#40;25&#8211;40&#37;&#41;&#44; 3<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>moderate &#40;40&#8211;55&#37;&#41;&#44; 4&#58; severe &#40;&#62;50&#37;&#41; with a maximum score of 40 for each kidney sample&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Sections were scored by two blind observer &#40;Kumas&#44; M and Esrefoglu&#44; M&#46;&#41; using a Nikon Eclipse i5 light microscope with a Nikon DS-Fi1c camera&#44; and Nikon NIS Elements version 4&#46;0 image analysis systems &#40;Nikon Instruments Inc&#46;&#44; Tokyo&#44; Japan&#41;&#46;</p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Biochemical analysis</span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Oxidative stress parameters</span><p id="par0080" class="elsevierStylePara elsevierViewall">Oxidative stress parameters including total antioxidant status &#40;TAS&#41; and total oxidant status &#40;TOS&#41; levels were determined by using an automatic biochemical analyzer &#40;c800&#44; Abbott&#44; USA&#41;&#46; Tissue TAS level was determined by Erel<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">18&#44;19</span></a>&#46; After this assay relied on the ability of antioxidants in the sample to inhibit ABTS &#40;2&#44;2&#8242;-azino-di-3-ethylbenz-thiazoline sulfonate&#41; from being oxidized into ABTS&#43; by a peroxidase metmyoglobin&#46; An antioxidant with a known concentration &#40;1&#46;65<span class="elsevierStyleHsp" style=""></span>mmol&#47;l&#41; was used as the standard to calculate antioxidant levels in the samples&#46; The TAS level was expressed as mmol Trolox equivalent&#47;l &#40;mmol Trolox equiv&#46;&#47;l&#41;&#46; The tissue TOS level was measured by Erel&#46;<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">19&#44;20</span></a> TOS method which relied on the oxidation of ferrous ions into ferric ions in the presence of various oxidative species in an acidic medium&#46; Ferric ion concentrations were measured by xylenol orange&#46; The assay was calibrated with a standard hydrogen peroxide solution &#40;39&#46;16<span class="elsevierStyleHsp" style=""></span>&#956;mol&#47;l&#41;&#46; Results were expressed as &#956;mol H<span class="elsevierStyleInf">2</span>O<span class="elsevierStyleInf">2</span> equivalent&#47;l &#40;&#956;mol H<span class="elsevierStyleInf">2</span>O<span class="elsevierStyleInf">2</span> equiv&#46;&#47;l&#41;&#46; The TOS&#47;TAS ratio was defined as oxidative stress index &#40;OSI&#41;&#46;</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Immunoblot assays</span><p id="par0085" class="elsevierStylePara elsevierViewall">Kidney tissues were homogenized in RIPA buffer &#40;50<span class="elsevierStyleHsp" style=""></span>mmol&#47;l Tris&#8211;HCl&#44; pH 7&#46;4&#44; 150<span class="elsevierStyleHsp" style=""></span>mmol&#47;l NaCl&#44; 5<span class="elsevierStyleHsp" style=""></span>mmol&#47;l EDTA&#44; 1&#37; Nonidet P-40&#44; 1&#37; sodium deoxycholate&#44; 0&#46;1&#37; SDS&#44; 1&#37; aprotinin&#44; 50<span class="elsevierStyleHsp" style=""></span>mmol&#47;l NaF&#44; 0&#46;1<span class="elsevierStyleHsp" style=""></span>mmol&#47;l Na<span class="elsevierStyleInf">3</span>VO<span class="elsevierStyleInf">4</span>&#41;&#44; and proteinase inhibitor cocktail &#40;Merck KGaA&#44; Darmstadt&#44; Germany&#41;&#46; After centrifugation at 14&#44;000<span class="elsevierStyleHsp" style=""></span>rpm &#40;Beckman Coulter&#44; Krefeld&#44; Germany&#41; for 10<span class="elsevierStyleHsp" style=""></span>min at 4<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; the final supernatant was used as the total protein&#46; Protein concentrations were determined using the Bradford method&#44; then all protein samples were equilibrated at 40<span class="elsevierStyleHsp" style=""></span>mg&#47;ml with loading buffer &#40;4&#37; SDS&#44; 10&#37; 2-mercaptoethanol&#44; 20&#37; glycerol&#44; 0&#46;004<span class="elsevierStyleHsp" style=""></span>M Tris&#8211;HCl&#44; pH 6&#46;8&#41; and loaded 8&#37; and 12&#37; sodium dodecyl sulfate polyacrylamide gel wells as 30<span class="elsevierStyleHsp" style=""></span>&#956;l&#44; transferred onto a polyvinylidene difluoride membrane &#40;PVDF&#41;&#44; and then incubated with primary antibodies including Anti-&#946; Actin Anti-Bax&#44; and Anti-Bcl 2 in a solution containing 5&#37; powdered skim milk and 0&#46;05&#37; Triton X-100&#47;TBS&#44; and washed three times in TBS-T for 10<span class="elsevierStyleHsp" style=""></span>min each&#46; Blots were incubated with a horse radish peroxidase &#40;HRP&#41;-conjugated goat anti-rabbit IgG at a concentration of 1<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml in 5&#37; powdered skim milk in 0&#46;05&#37; TBS-T&#46; Protein bands were visualized with Pierce ECL Western blotting substrate &#40;Thermo Scientific&#41;&#46; Protein bands were visualized using the enhanced chemiluminescence detection system &#40;Vilber Lourmat Fx7&#44; Coll&#233;gien&#44; France&#41; and analyzed with Image J software&#46;</p><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Enzyme-linked ImmunoSorbent Assay &#40;ELISA&#41;</span><p id="par0090" class="elsevierStylePara elsevierViewall">Serum and tissue samples were thawed and ELISA kits were used for the quantitative measurement of Rat TNF alpha&#44; CRP&#44; and BUN&#46; Optical density was read on a standard automated plate reader at 450<span class="elsevierStyleHsp" style=""></span>nm &#40;Perkin Elmer&#44; 1420 Victor 3&#41;&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Assays of lactate dehydrogenase &#40;LDH&#41; and creatinine</span><p id="par0095" class="elsevierStylePara elsevierViewall">Serum LDH and creatinine levels were detected by colorimetric method using microplate reader &#40;Perkin Elmer&#44; 1420 Victor 3&#41;&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Assessment of Na-K-ATPase and Ca-ATPase</span><p id="par0100" class="elsevierStylePara elsevierViewall">Na-K-ATPase and Ca-ATPase levels were measured with ELISA test in kidney tissues&#46; The ELISA assays performed with proteins which isolated from homogenized tissues according to manufacturer&#39;s instructions&#46; Results were expressed in nanogram per milliliter of 1<span class="elsevierStyleHsp" style=""></span>mg total protein&#46;</p></span></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Statistical analysis</span><p id="par0105" class="elsevierStylePara elsevierViewall">Normality of the all data was tested with Shapiro&#8211;Wilk normality test&#44; because of our sample size of less than 50&#46; Data have a normal distribution &#40;Shapiro&#8211;Wilk test&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41; was analyzed by parametric test ANOVA &#40;post hoc Tukey&#39;s HSD&#41; for multiple comparisons&#44; while non-normal distributed data &#40;Shapiro&#8211;Wilk test&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41; was analyzed by Kruskal&#8211;Wallis test for multiple comparison and Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test for comparing two groups&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Values are presented as minimum&#44; maximum and median for non-parametric data&#44; while as mean<span class="elsevierStyleHsp" style=""></span>&#177; standard deviation &#40;SD&#41; for parametric data&#46; <span class="elsevierStyleItalic">p</span> values<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>0&#46;05 were approved as statistically significant&#46; Statistical analyses were done with SPSS 20&#46;0 &#40;IBM&#44; New York&#44; USA&#41; and MS Office Excel&#46; Graph Pad Prism 6 was used for drawing bar charts&#46;</p></span></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Results</span><p id="par0115" class="elsevierStylePara elsevierViewall">We examined both left and right kidney for histological and biochemical analysis&#44; and compared all results&#46; We did not find any important differences in terms of all evaluated parameters among left and right kidneys&#46; Thus&#44; we preferred to mention only pathological alterations observed in left kidneys&#46;</p><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Assessment of histopathological alterations</span><p id="par0120" class="elsevierStylePara elsevierViewall">The results about histopathological scores of the all of the groups are presented in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0125" class="elsevierStylePara elsevierViewall">The highest proximal tubular damage scores including tubular dilation and atrophy &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>a&#41;&#44; loss of brush border &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>b&#41;&#44; and tubular necrosis &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>c&#41; were detected in STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group&#46; The median scores of each of those of alterations were also statistically higher in STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group than STZ group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;007&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;003&#44; and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;004&#44; respectively&#41;&#46; Proximal tubular damage seen in STZ group was severely aggravated after IRI&#46; 50<span class="elsevierStyleHsp" style=""></span>mg dose of BRB administration was not improved proximal tubular dilation and atrophy&#44; and tubular necrosis in STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">1</span> group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#44; <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>a and b&#41;&#44; whereas the loss of brush border score was significantly decreased in that group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;011&#41;&#46; All of those alterations improved after 100<span class="elsevierStyleHsp" style=""></span>mg and 150<span class="elsevierStyleHsp" style=""></span>mg BRB administration in STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">2</span> &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;004&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;003&#44; and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;007&#44; respectively&#59; <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>c&#41; and STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">3</span> groups &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;004&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;003&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;004&#44; respectively&#59; <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>d&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0130" class="elsevierStylePara elsevierViewall">Distal tubular damage including tubular dilation and atrophy &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>a&#41;&#44; and tubular necrosis &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>c&#41; severely increased in STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group compared to STZ group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;008 and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;005&#44; respectively&#41;&#46; In both STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">2</span> and STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">3</span> groups&#44; distal tubular dilation and atrophy scores markedly decreased when compared to STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;012 and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;004&#44; respectively&#59; <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>c and d&#41;&#46; Distal tubular necrosis score reduced in STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">3</span> &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;008&#59; <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>c and d&#41;&#44; but it was not detected any statistically significant alteration in other berberine administrated groups &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; Thyroidization which is the similarity of the tubules&#44; accumulating acidophilic and PAS positive material within the lumen&#44; with thyroid follicles was observed in two sections &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>a&#41;&#46; Brown hemosiderin granules accompanied by mononuclear cell infiltration in the necrotic area were also observed &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>c&#41;&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Glomerular basement membrane seemed to be thickened in STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group compared to STZ group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;027&#44; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>d&#41;&#46; Berberine administration was effective in normalization of the basement membrane in STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">2</span> and STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">3</span> &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;014&#44; for both&#41;&#46; Fibrosis and mononuclear cell infiltration related with interstitial damage were observed in STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group&#46; When compared to STZ group&#44; mononuclear cell infiltration score was markedly increased in STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;008&#44; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>c and d&#41;&#46; Berberine administration at all doses significantly improved those scores &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; Fibrosis was sometimes observed in STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group&#44; but it occupied large area in only one sample &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>c&#41;&#46; Berberine administrations had no significant effect on fibrosis&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Congestion and dilatation of the capillaries were even for per sample so were collectively scored &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>f&#41;&#46; The highest median score was detected in STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41;&#46; All doses of berberine resulted in decrease in congestion scores &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;014&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;004&#44; and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;003&#44; respectively&#41;&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">The highest total histopathological score was detected in STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;004&#41;&#46; The scores of STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">2</span>&#44; and STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">3</span> groups &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;004&#44; for both&#41; were lower than that of STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group&#46;</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Assessment of biochemical alterations</span><p id="par0150" class="elsevierStylePara elsevierViewall">The results of biochemical parameters of all of the groups are represented in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Assessment of kidney function</span><p id="par0155" class="elsevierStylePara elsevierViewall">Serum BUN and creatinine levels which are the markers for kidney functions were evaluated &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; The mean BUN and creatinine levels were markedly higher in STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group than that of STZ group&#46; Those levels significantly decreased after berberine administration in all berberine administrated groups &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; except mean serum creatinine level which was not significantly changed between STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">1</span> and STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Assessment of oxidative stress</span><p id="par0160" class="elsevierStylePara elsevierViewall">The highest mean TOS was detected in STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>RIR group &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46; The levels in berberine administrated groups were statistically lower than that of STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#44; for all comparisons&#41;&#46; The lowest mean total antioxidant status &#40;TAS&#41; was detected in STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46; Berberine administration gradually increased antioxidant status in a dose dependent manner when compared to STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>RIR group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#44; for all groups&#41;&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0165" class="elsevierStylePara elsevierViewall">Oxidative stress index was calculated as ratio of TOS and TAS&#46; OSI in STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group was considerably higher than the other groups &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46; OSI decreased in berberine administrated groups &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#44; for all groups&#41;&#46; According to these results&#44; berberine markedly suppressed oxidative stress via stimulating antioxidant system&#46;</p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0185">Assessment of lactate dehydrogenase</span><p id="par0170" class="elsevierStylePara elsevierViewall">The mean serum LDH level which is a marker for tubular necrosis was higher in STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group than that of STZ group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#44; <a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>&#41;&#46; The levels in STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">1</span>&#44; STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">2</span>&#44; and STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">3</span> groups were significantly lower than STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#44; for all of comparisons&#41;&#46;</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0190">Assessment of inflammation markers</span><p id="par0175" class="elsevierStylePara elsevierViewall">The highest mean TNF-&#945; and CRP levels were detected in STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group compared to STZ &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; and the other groups&#46; The levels gradually decreased in berberine administrated groups including STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">1</span>&#44; STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">2</span>&#44; and STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">3</span> groups &#40;<a class="elsevierStyleCrossRef" href="#fig0030">Fig&#46; 6</a>&#41;&#46;</p><elsevierMultimedia ident="fig0030"></elsevierMultimedia><p id="par0180" class="elsevierStylePara elsevierViewall">Berberine significantly showed an anti-inflammatory effect against renal ischemia injury via reducing tissue levels of TNF-&#945; and CRP &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46;</p></span><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0195">Assessment of apoptosis</span><p id="par0185" class="elsevierStylePara elsevierViewall">Expression of pro-apoptotic Bax protein significantly increased but expression of anti-apoptotic Bcl-2 protein decreased in STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group compared to the other groups &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#44; <a class="elsevierStyleCrossRef" href="#fig0035">Fig&#46; 7</a>&#41;&#46; IRI markedly caused apoptosis via inducing pro-apoptotic protein&#44; and suppressing anti-apoptotic protein &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; Berberine administrations at the doses of 100<span class="elsevierStyleHsp" style=""></span>mg&#47;kg and 150<span class="elsevierStyleHsp" style=""></span>mg&#47;kg increased expression of pro-apoptotic Bcl-2 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; but berberine at a dose of 50<span class="elsevierStyleHsp" style=""></span>mg&#47;kg in STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">1</span> did not perform any anti-apoptotic effect compared to STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group&#46;</p><elsevierMultimedia ident="fig0035"></elsevierMultimedia></span><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0200">Assessment of Ca<span class="elsevierStyleSup">2&#43;</span> ATPase and Na<span class="elsevierStyleSup">&#43;</span>&#47;K<span class="elsevierStyleSup">&#43;</span>-ATPase enzyme activities</span><p id="par0190" class="elsevierStylePara elsevierViewall">The mean tissue Ca<span class="elsevierStyleSup">2&#43;</span> ATPase enzyme activity was markedly lower in STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group than that of STZ group&#46; The highest mean Ca<span class="elsevierStyleSup">2&#43;</span> ATPase enzyme activity was detected in STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">3</span>&#46; Berberine administration at a dose of 150<span class="elsevierStyleHsp" style=""></span>mg&#47;kg significantly increased that enzyme activity &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#44; <a class="elsevierStyleCrossRef" href="#fig0040">Fig&#46; 8</a>&#41;&#46; The mean tissue Na<span class="elsevierStyleSup">&#43;</span>&#47;K<span class="elsevierStyleSup">&#43;</span>-ATPase enzyme activity was detected as 13&#46;38<span class="elsevierStyleHsp" style=""></span>&#177; 1&#46;21 in STZ group while 10&#46;94<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;47 in STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; The activity of this enzyme in STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">2</span> group was significantly higher than that of STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;039&#44; <a class="elsevierStyleCrossRef" href="#fig0040">Fig&#46; 8</a>&#41;&#46;</p><elsevierMultimedia ident="fig0040"></elsevierMultimedia></span></span><span id="sec0135" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0205">Discussion</span><p id="par0195" class="elsevierStylePara elsevierViewall">Acute kidney injury &#40;AKI&#41; or renal failure has been described as a rapid dysfunction of the kidney&#46; Ischemia&#47;reperfusion injury is the most important reason of acute renal failure&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">21&#44;22</span></a> Diabetes mellitus is also an important risk factor for the renal failure&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">4</span></a> Animal models have been widely for understanding mechanisms of IRI&#46; It was recorded that IRI has resulted in serious histopathological and biochemical damages in both patients and experimental animals&#46;<a class="elsevierStyleCrossRefs" href="#bib0365"><span class="elsevierStyleSup">23&#8211;25</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">BUN and serum creatinine levels are the most commonly used markers evaluating renal function&#46; Significantly increased BUN and creatinine levels are typical indicators of AKI&#46;<a class="elsevierStyleCrossRefs" href="#bib0380"><span class="elsevierStyleSup">26&#8211;29</span></a> We detected significantly increased BUN and creatinine levels in ischemic diabetic group&#46; These levels were decreased in BRB administrated groups&#46; Those decreases might show the beneficial effect of berberine on kidney functions&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">Especially re-oxygenation of tissue after hypoxia seriously causes accumulation of free radicals&#44; known as oxidative stress&#46; Both ischemia and hyperglycemia aggravate production of reactive oxygen species &#40;ROS&#41;&#44; and it is possible that the two factors precipitate each other&#46;<a class="elsevierStyleCrossRefs" href="#bib0400"><span class="elsevierStyleSup">30&#44;31</span></a> Clinical and experimental studies showed that diabetes increased the degree of ischemic injury&#46;<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">16&#44;31&#44;32</span></a> Measurement of TOS and TAS is a crucial biomarker to evaluate oxidative damage&#46;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">31&#8211;33</span></a> Since tissue TOS level was markedly increased in STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group we suggest that IRI induces oxidative stress&#46; Conversely since all doses of BRB decreased TOS level but increased TAS level&#44; we suggest that BRB is effective in reducing oxidative stress and damage induced by IRI in diabetic rats&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">In the current study&#44; we detected serious histopathological damages including tubular&#44; glomerular&#44; interstitial&#44; and vascular damage in diabetic rats after IRI in accordance with previous studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">4&#44;5&#44;10&#44;28</span></a> Proximal and distal tubular damage was more obvious than glomerular damage as previously reported&#46;<a class="elsevierStyleCrossRefs" href="#bib0420"><span class="elsevierStyleSup">34&#8211;36</span></a> Endothelial damage in peritubular capillaries caused by vascular congestion&#44; and leukocyte infiltration was reported after IRI&#46;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">10&#44;22&#44;24&#44;25</span></a> We observed that dilatation and congestion of the capillaries were even for per sample&#46; Mononuclear cell infiltration accompanied by necrosis occupied large area in ischemic group&#46; The glomerular basement membrane in STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group was thicker than those of the other groups&#46; BRB&#44; in a dose-dependent manner&#44; improved histopathological findings&#59; the most effective dose was 150<span class="elsevierStyleHsp" style=""></span>mg&#47;kg for tissue healing after IRI&#46; Even the decrease in total pathological score at a dose of 50<span class="elsevierStyleHsp" style=""></span>mg&#47;kg BRB administrated group was evident&#44; it was not statistically significant&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">Tubular necrosis was obvious in diabetic ischemic group&#46; LDH is an important indicator for necrosis thus increased levels of LDH in serum indicates plasma membrane damage&#46;<a class="elsevierStyleCrossRefs" href="#bib0430"><span class="elsevierStyleSup">36&#44;37</span></a> Following IRI&#44; we detected significantly increased LDH levels concomitant with severe tubular damage&#46; Necrotic cell death stimulates inflammatory responses&#46;<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">6&#44;22</span></a> Hence inflammation has been observed generally together with necrosis induced by IRI&#46; TNF-&#945;&#44; TGF-&#946; and CRP have been widely used as inflammation markers&#46; The serum concentrations of those markers increase after acute or chronic renal injury associated with diabetes&#46;<a class="elsevierStyleCrossRefs" href="#bib0390"><span class="elsevierStyleSup">28&#44;38&#44;39</span></a> In the present study TNF-&#945; and CRP level in IRI group were markedly increased in diabetic rats&#46; It was mentioned in previous studies that BRB has anti-inflammatory effect via inhibiting inflammatory markers&#46;<a class="elsevierStyleCrossRefs" href="#bib0450"><span class="elsevierStyleSup">40&#44;41</span></a> In current study&#44; BRB showed similar anti-inflammatory effect against IRI in all berberine administrated groups via decreasing levels of TNF-&#945; and CRP&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">Diabetes and ischemia both&#44; significantly induces apoptotic cell death&#46;<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">25&#44;42</span></a> In ischemic tissue&#44; pro-apoptotic Bax protein level significantly increased while anti-apoptotic Bcl2 protein level decreased in diabetic rats&#46; BRB administration at the doses of 100<span class="elsevierStyleHsp" style=""></span>mg&#47;kg and 150<span class="elsevierStyleHsp" style=""></span>mg&#47;kg showed significant anti-apoptotic effect via suppressing anti-apoptotic protein&#44; while BRB administration at a dose of 50<span class="elsevierStyleHsp" style=""></span>mg&#47;kg was not effective as well as other doses&#46; Visnagri et al&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">28</span></a> demonstrated that BRB at the doses of 20<span class="elsevierStyleHsp" style=""></span>mg&#47;kg and 40<span class="elsevierStyleHsp" style=""></span>mg&#47;kg has similar anti-apoptotic effect in non-diabetic rats&#46; During hypoxia&#44; as a result of cellular damage&#44; intracellular calcium level dramatically increases&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">43</span></a> The Ca<span class="elsevierStyleSup">2&#43;</span>-ATPase&#40;s&#41; enzyme found in the plasma membrane and endoplasmic reticulum has an important role in maintaining the intracellular Ca<span class="elsevierStyleSup">2&#43;</span> level&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">44</span></a> In our study Ca<span class="elsevierStyleSup">2&#43;</span>-ATPase enzyme level significantly decreased after IRI in diabetic rats&#46; We suggest that decrease of Ca<span class="elsevierStyleSup">2&#43;</span>-ATPase leads to increase of intracellular Ca<span class="elsevierStyleSup">2&#43;</span> concentration&#46; Conversely&#44; Visnagri et al&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">28</span></a> have suggested that ischemia induces apoptosis&#44; and Ca<span class="elsevierStyleSup">2&#43;</span>-ATPase enzyme level increases in ischemic group&#46; We detected decreased levels of Ca<span class="elsevierStyleSup">2&#43;</span>-ATPase in STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group&#46; Increase in intracellular Ca<span class="elsevierStyleSup">2&#43;</span> is an indicator of apoptotic cell death&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">45</span></a> Anti-apoptotic Bcl 2 has a crucial function on Ca<span class="elsevierStyleSup">2&#43;</span> homeostasis&#46; Bcl-2 overexpression causes decreased Ca<span class="elsevierStyleSup">2&#43;</span> releasing from endoplasmic reticulum&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">45</span></a> As we mentioned before&#44; expression of Bcl2 level decreased in ischemic group&#46; Both decreasing of Ca<span class="elsevierStyleSup">2&#43;</span>-ATPse enzyme and Bcl2 levels indicated that renal tissue cell sustained apoptotic cell death&#46; In contrast to STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group&#44; BRB showed anti-apoptotic effect via increasing Ca<span class="elsevierStyleSup">2&#43;</span>-ATPase enzyme and Bcl 2 protein levels&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">The Na<span class="elsevierStyleSup">&#43;</span>&#47;K<span class="elsevierStyleSup">&#43;</span>-ATPase enzyme&#44; known as energy-dependent sodium pump&#44; transports Na<span class="elsevierStyleSup">&#43;</span> into and K<span class="elsevierStyleSup">&#43;</span> out of the cell against their concentration gradients&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">46</span></a> This pump is essential for the maintenance of Na<span class="elsevierStyleSup">&#43;</span> and K<span class="elsevierStyleSup">&#43;</span> concentrations across the membrane&#46; When this pump stops working or destroys&#44; Na<span class="elsevierStyleSup">&#43;</span> accumulates in cytoplasm&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">42</span></a> Tubular epithelial cell polarity thus fluid&#47;ion transport are significantly destroyed after IRI&#46; It has been shown in several organs including kidney&#44; myocardium&#44; brain&#44; hippocampus&#44; etc&#46; that ischemia injury resulted in decrease in the levels of Na<span class="elsevierStyleSup">&#43;</span>&#47;K<span class="elsevierStyleSup">&#43;</span>-ATPase enzyme&#46;<a class="elsevierStyleCrossRefs" href="#bib0395"><span class="elsevierStyleSup">29&#44;47&#8211;50</span></a> IRI markedly caused in decline of Na<span class="elsevierStyleSup">&#43;</span>&#47;K<span class="elsevierStyleSup">&#43;</span>-ATPase level in diabetic rats&#44; and BRB administration at a dose of 100<span class="elsevierStyleHsp" style=""></span>mg&#47;kg significantly increased that of enzyme level&#46;</p></span><span id="sec0140" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0210">Conclusion</span><p id="par0230" class="elsevierStylePara elsevierViewall">As a conclusion berberine administration following ischemia&#47;reperfusion markedly improved histopathological findings&#44; prevented necrotic cell death&#46; Berberine normalized kidney function via decreasing BUN and creatinine levels&#46; Berberine showed also anti-oxidant&#44; anti-apoptotic&#44; and anti-inflammatory effect&#46; According to these data we suggest that berberine at the doses of 100 and 150<span class="elsevierStyleHsp" style=""></span>mg may be used as a potential therapeutic agent against renal ischemic injury&#46;</p></span><span id="sec0145" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0215">Conflict of interest</span><p id="par0235" class="elsevierStylePara elsevierViewall">All authors declared that they have no conflict of interest&#46;</p></span><span id="sec0150" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0220">Funding</span><p id="par0240" class="elsevierStylePara elsevierViewall">This work was supported by the <span class="elsevierStyleGrantSponsor" id="gs1">Bezmialem Vakif University Scientific Research Project Foundation</span> &#91;grant number <span class="elsevierStyleGrantNumber" refid="gs1">6&#46;2017&#47;8</span>&#93;&#46;</p></span></span>"
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              "titulo" => "Background"
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          "titulo" => "Introduction"
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                  "titulo" => "Animals"
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                1 => array:2 [
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                  "titulo" => "Diabetes induction"
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                  "titulo" => "Renal ischemia&#47;reperfusion procedure"
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                  "titulo" => "Berberine administration"
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              "titulo" => "Histological analysis"
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                  "titulo" => "Scoring system for evaluation of the kidney injury"
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              "titulo" => "Biochemical analysis"
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              "titulo" => "Immunoblot assays"
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                  "titulo" => "Enzyme-linked ImmunoSorbent Assay &#40;ELISA&#41;"
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                  "identificador" => "sec0075"
                  "titulo" => "Assays of lactate dehydrogenase &#40;LDH&#41; and creatinine"
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                  "titulo" => "Assessment of Na-K-ATPase and Ca-ATPase"
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          "titulo" => "Results"
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              "identificador" => "sec0095"
              "titulo" => "Assessment of histopathological alterations"
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              "identificador" => "sec0100"
              "titulo" => "Assessment of biochemical alterations"
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              "identificador" => "sec0105"
              "titulo" => "Assessment of kidney function"
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              "identificador" => "sec0110"
              "titulo" => "Assessment of oxidative stress"
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              "identificador" => "sec0115"
              "titulo" => "Assessment of lactate dehydrogenase"
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              "identificador" => "sec0120"
              "titulo" => "Assessment of inflammation markers"
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              "identificador" => "sec0125"
              "titulo" => "Assessment of apoptosis"
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              "identificador" => "sec0130"
              "titulo" => "Assessment of Ca ATPase and Na&#47;K-ATPase enzyme activities"
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          "titulo" => "Discussion"
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    "fechaRecibido" => "2018-07-16"
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            0 => "Renal ischemia&#47;reperfusion injury"
            1 => "Berberine"
            2 => "Histopathology"
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            5 => "Inflammation"
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            0 => "Insuficiencia renal por isquemia&#47;reperfusi&#243;n"
            1 => "Berberina"
            2 => "Histopatolog&#237;a"
            3 => "Estr&#233;s oxidativo"
            4 => "Apoptosis"
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    "resumen" => array:2 [
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Ischemia&#8211;reperfusion injury causes various severe morphological and functional changes in diabetic patients&#46; To date&#44; numerous antidiabetic and antioxidant agents have been used for treatment of the disease-related changes&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objectives</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We aimed to examine effective therapeutic doses or doses of berberine against renal ischemia&#47;reperfusion injury &#40;IRI&#41; in a streptozotocin &#40;STZ&#41;-induced diabetic rat model by histopathological and biochemical analysis&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Thirty male Sprague Dawley rats were treated with STZ injection for the development of diabetes&#44; and divided into the following groups&#58; STZ-induced diabetic group &#40;STZ&#41;&#59; IRI-induced diabetic group &#40;STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI&#41;&#59; 50<span class="elsevierStyleHsp" style=""></span>mg&#47;kg berberine &#40;BRB&#41; treated diabetic group after inducing IRI &#40;STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">1</span>&#41;&#59; 100<span class="elsevierStyleHsp" style=""></span>mg&#47;kg BRB treated diabetic group after IRI &#40;STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">2</span>&#41;&#59; 150<span class="elsevierStyleHsp" style=""></span>mg&#47;kg BRB treated diabetic group after IRI &#40;STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">3</span>&#41;&#46; Bilateral renal ischemia model was applied for 45<span class="elsevierStyleHsp" style=""></span>min&#44; then reperfusion was allowed for 14 days in STZ-induced diabetic rats&#46; Renal injury was detected histopathologically&#46; Blood urea nitrogen &#40;BUN&#41;&#44; creatinine and lactate dehydrogenase &#40;LDH&#41; levels were measured in serum using the ELISA method&#46; Total antioxidant status &#40;TAS&#41; and total oxidant status &#40;TOS&#41; of renal tissue was studied by spectrophotometric assay&#46; Oxidative stress index &#40;OSI&#41; was calculated as TOS-to-TAS ratio&#46; Tumor necrosis factor alpha &#40;TNF-&#945;&#41;&#44; C-reactive protein &#40;CRP&#41;&#44; Na<span class="elsevierStyleSup">&#43;</span>&#47;K<span class="elsevierStyleSup">&#43;</span>-ATPase &#40;sodium pump&#41;&#44; and Ca<span class="elsevierStyleSup">2&#43;</span>-ATPase &#40;calcium ATPase&#41; enzyme levels were measured in tissues using the ELISA method&#46; Anti-apoptotic Bax and pro-apoptotic Bcl-2 protein levels were detected by Western blot analysis&#46; All data were evaluated statistically&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The highest histopathological score was detected in the STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group compared to the other group&#46; BRB administration at the doses of 100<span class="elsevierStyleHsp" style=""></span>mg&#47;kg and 150<span class="elsevierStyleHsp" style=""></span>mg&#47;kg markedly improved renal injury&#46; BUN and creatinine levels significantly increased in the STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group compared to the STZ group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; 100<span class="elsevierStyleHsp" style=""></span>mg&#47;kg and 150<span class="elsevierStyleHsp" style=""></span>mg&#47;kg BRB administration significantly decreased those levels &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#46; The highest TOS and the lowest TAS levels were detected in the STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; IRI markedly aggravated inflammation via increasing levels of TNF-&#945; and CRP &#40;&#60;0&#46;001&#41;&#44; and caused apoptosis via inducing Bcl-2 protein&#44; and suppressing Bax protein &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; BRB administration at the doses of 100<span class="elsevierStyleHsp" style=""></span>mg&#47;kg and 150<span class="elsevierStyleHsp" style=""></span>mg&#47;kg showed anti-oxidant&#44; anti-inflammatory and anti-apoptotic effects &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#46; The LDH enzyme&#44; was used as a necrosis marker&#44; was higher in the STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group than other groups&#46; BRB administration at all of the doses&#44; resulted in the decline of LDH enzyme level &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; Ca<span class="elsevierStyleSup">2&#43;</span>-ATPase and Na<span class="elsevierStyleSup">&#43;</span>&#47;K<span class="elsevierStyleSup">&#43;</span>-ATPase enzyme activities decreased in the STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group compared to the STZ group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; while BRB administration at the doses of 100<span class="elsevierStyleHsp" style=""></span>mg&#47;kg and 150<span class="elsevierStyleHsp" style=""></span>mg&#47;kg significantly increased those of enzyme activities&#44; respectively &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusion</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Ischemia with diabetes caused severe histopathological and biochemical damage in renal tissue&#46; The high doses of berberine markedly improved histopathological findings&#44; regulated kidney function via decreasing BUN and creatinine levels&#44; and rearranged intercellular ion concentration via increasing Na<span class="elsevierStyleSup">&#43;</span>&#47;K<span class="elsevierStyleSup">&#43;</span>-ATPase and Ca<span class="elsevierStyleSup">2&#43;&#8722;</span> ATPase levels&#46; Berberine showed anti-oxidant&#44; anti-apoptotic&#44; and anti-inflammatory effects&#46; According to these data&#44; we suggest that berberine at the doses of 100 and 150<span class="elsevierStyleHsp" style=""></span>mg may be used as a potential therapeutic agent to prevent renal ischemic injury&#46;</p></span>"
        "secciones" => array:5 [
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            "titulo" => "Background"
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          1 => array:2 [
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            "titulo" => "Objectives"
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          2 => array:2 [
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            "titulo" => "Methods"
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Antecedentes</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">La reperfusi&#243;n de la isquemia provoca graves cambios morfol&#243;gicos y funcionales en los pacientes diab&#233;ticos&#46; Hasta la fecha numerosos antidiab&#233;ticos y agentes antioxidantes han sido utilizados para el tratamiento de los cambios relacionados con la enfermedad&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">El objetivo fue examinar las dosis terap&#233;uticas efectivas o las dosis de berberina &#40;BRB&#41; frente a la insuficiencia renal por isquemia&#47;reperfusi&#243;n &#40;IRI&#41; en estreptozotocina &#40;STZ&#41; inducida por el modelo de rata por an&#225;lisis histopatol&#243;gico y bioqu&#237;mico&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Treinta ratas machos Spraque-Dawley fueron tratadas con inyecci&#243;n de STZ para el desarrollo de diabetes&#44; se dividieron en los siguientes grupos&#58; grupo diab&#233;tico inducido por STZ&#59; grupo diab&#233;tico inducido por IRI &#40;STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI&#41;&#59; grupo diab&#233;tico tratado con 50<span class="elsevierStyleHsp" style=""></span>mg&#47;kg de BRB despu&#233;s de la inducci&#243;n de IRI &#40;STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">1</span>&#41;&#59; grupo diab&#233;tico tratado con 100<span class="elsevierStyleHsp" style=""></span>mg&#47;kg de BRB despu&#233;s de IRI &#40;STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">2</span>&#41;&#44; y grupo diab&#233;tico tratado con 150<span class="elsevierStyleHsp" style=""></span>mg&#47;kg de BRB despu&#233;s de IRI &#40;STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">3</span>&#41;&#46; Se aplic&#243; un modelo de isquemia renal bilateral durante 45<span class="elsevierStyleHsp" style=""></span>min&#44; luego se permiti&#243; la reperfusi&#243;n durante 14 d&#237;as en ratas diab&#233;ticas inducidas por STZ&#46; La lesi&#243;n renal fue detectada histopatol&#243;gicamente&#46; Los niveles de nitr&#243;geno ureico en sangre &#40;BUN&#41;&#44; creatinina y lactato deshidrogenasa &#40;LDH&#41; se midieron en suero por el m&#233;todo ELISA&#46; El estado antioxidante total &#40;TAS&#41; y el estado oxidante total &#40;TOS&#41; del tejido renal se estudiaron mediante un ensayo espectrofotom&#233;trico&#46; El &#237;ndice de estr&#233;s oxidativo &#40;OSI&#41; fue calculado como la relaci&#243;n TOS-a-TAS&#46; El factor de necrosis tumoral alfa &#40;TNF-&#945;&#41;&#44; prote&#237;na C reactiva &#40;CRP&#41;&#44; Na<span class="elsevierStyleSup">&#43;</span>&#47;K<span class="elsevierStyleSup">&#43;</span>-ATPasa &#40;bomba de sodio&#41; y la Ca<span class="elsevierStyleSup">2&#43;</span>-ATPasa &#40;calcio ATPasa&#41; de la enzima se midieron los niveles en los tejidos mediante el m&#233;todo ELISA&#46; Los niveles de prote&#237;na anti-apopt&#243;tica Bax y pro-apopt&#243;tica Bcl-2 se detectaron por el an&#225;lisis de <span class="elsevierStyleItalic">Western blot</span>&#46; Todos los datos fueron evaluados estad&#237;sticamente&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">La mayor puntuaci&#243;n histopatol&#243;gica fue detectada en el grupo STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI en comparaci&#243;n con el otro grupo&#46; La administraci&#243;n de BRB en dosis de 100 y 150<span class="elsevierStyleHsp" style=""></span>mg&#47;kg mejor&#243; notablemente la lesi&#243;n renal&#46; Los niveles de BUN y creatinina aumentaron significativamente en el grupo STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI en comparaci&#243;n con el grupo STZ &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; La administraci&#243;n de 100 y 150<span class="elsevierStyleHsp" style=""></span>mg&#47;kg de BRB disminuy&#243; significativamente esos niveles &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#41;&#46; Los TOS m&#225;s altos y los niveles m&#225;s bajos de TAS se detectaron en el grupo STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; El IRI agrav&#243; notablemente la inflamaci&#243;n a trav&#233;s del aumento de los niveles de TNF-alfa y de PCR &#40;&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; y caus&#243; la apoptosis a trav&#233;s de la inducci&#243;n de la prote&#237;na Bcl-2 y la supresi&#243;n de la prote&#237;na Bax &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; La administraci&#243;n de BRB con las dosis de 100 y 150<span class="elsevierStyleHsp" style=""></span>mg&#47;kg mostr&#243; efectos antioxidante&#44; antiinflamatorio y antiapopt&#243;ticos &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#41;&#46; La enzima LDH que se us&#243; como marcador de necrosis fue mayor en el grupo STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI que en los otros grupos&#46; La administraci&#243;n de BRB en todas las dosis&#44; dio lugar a una disminuci&#243;n del nivel de la enzima LDH &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; Las actividades de las enzimas Ca<span class="elsevierStyleSup">2&#43;</span>-ATPasa y Na<span class="elsevierStyleSup">&#43;</span>&#47;K<span class="elsevierStyleSup">&#43;</span>-ATPasa disminuyeron en el grupo STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI en comparaci&#243;n con el grupo STZ &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#44; mientras que la administraci&#243;n de BRB en dosis de 100 y 150<span class="elsevierStyleHsp" style=""></span>mg&#47;kg increment&#243; significativamente las actividades de las enzimas&#44; respectivamente &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusi&#243;n</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">La isquemia con diabetes caus&#243; graves da&#241;os histopatol&#243;gicos y bioqu&#237;micos en el tejido renal&#46; Las altas dosis de BRB mejoraron notablemente los hallazgos histopatol&#243;gicos&#44; la funci&#243;n renal regulada a trav&#233;s de la disminuci&#243;n de los niveles de BUN y creatinina&#44; y la concentraci&#243;n de iones intercelulares reordenados mediante el aumento de los niveles de Na<span class="elsevierStyleSup">&#43;</span>&#47;K<span class="elsevierStyleSup">&#43;</span>-ATPasa y la Ca<span class="elsevierStyleSup">2&#43;</span>-ATPasa&#46; La BRB mostr&#243; efectos antioxidantes&#44; antiapopt&#243;ticos y antiinflamatorios&#46; De acuerdo con estos datos&#44; sugerimos que la BRB en dosis de 100 y 150<span class="elsevierStyleHsp" style=""></span>mg se puede usar como un agente terap&#233;utico potencial para prevenir la lesi&#243;n isqu&#233;mica renal&#46;</p></span>"
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          2 => array:2 [
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          3 => array:2 [
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Light microscopic figures of renal cortex in STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group&#46; &#40;a&#41; Tubular dilatation&#44; atrophy &#40;asterisks&#41;&#44; thyroidization &#40;black arrows&#41; and interstitial mononuclear cell infiltration &#40;yellow arrowheads&#41; are obvious&#46; Hematoxylin &#38; Eosin&#59; 20&#215;&#46; &#40;b&#41; Tubular degeneration &#40;dark blue arrowheads&#41; is obvious&#46; Basement membranes are not clearly seen&#44; brush border loss is prominent&#46; Periodic Acid Schiff&#59; 20&#215;&#46; &#40;c&#41; Tubular necrosis &#40;red arrowheads&#41; and interstitial cell infiltration &#40;yellow arrowheads&#41; are clearly seen&#46; Note that hemosiderin is accumulated within the area&#46; Hematoxylin &#38; Eosin&#59; 10&#215;&#46; &#40;d&#41; Interstitial mononuclear cell infiltration &#40;yellow arrowheads&#41; and glomerular and tubular basement membrane thickening is observed&#46; Periodic Acid Schiff&#59; 40&#215;&#46; &#40;e&#41; Tubular degeneration &#40;red arrowheads&#41;&#44; interstitial cell infiltration&#44; and fibrosis &#40;yellow arrows&#41; are seen&#46; Masson&#39;s trichrome 20&#215;&#46; &#40;f&#41; Capillary dilatation and congestion are observed&#46; Hematoxylin &#38; Eosin&#59; 20&#215;&#46;</p>"
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        "etiqueta" => "Fig&#46; 2"
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          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Histological sections of STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">1</span> &#40;a and b&#41;&#44; STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">2</span> &#40;c&#41;&#44; and STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">3</span> groups &#40;d&#41;&#46; Dose-dependent improvement on all of the histological alterations induced by diabetes &#40;STZ&#41; and ischemia reperfusion injury &#40;IRI&#41; is observed&#46; &#40;a&#41; and &#40;c&#41; Hematoxylin &#38; Eosin stain&#59; &#40;b&#41; and &#40;d&#41; Periodic Acid Schiff stain&#59; 20&#215;&#41;&#46;</p>"
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          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Mean serum blood urea nitrogen &#40;BUN&#41; and creatinine levels in all groups&#46; The data are expressed as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation &#40;&#42;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 vs&#46; STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group&#46; One way ANOVA&#44; post hoc Tukey test&#41;&#46;</p>"
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        "mostrarFloat" => true
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        "figura" => array:1 [
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          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Mean tissue total antioxidant status &#40;TAS&#41;&#44; total oxidant status &#40;TOS&#41; and oxidative stress index &#40;OSI&#41; in all groups&#46; The data are expressed as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation &#40;&#42;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 vs&#46; STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group&#46; One way ANOVA&#44; post hoc Tukey test&#41;&#46;</p>"
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        "mostrarFloat" => true
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          "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Mean serum lactate dehydrogenase level in all groups&#46; The data are expressed as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation &#40;&#42; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 vs&#46; STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group&#46; One way ANOVA&#44; post hoc Tukey test&#41;&#46;</p>"
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        "mostrarFloat" => true
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        "figura" => array:1 [
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          "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Mean tumor necrosis factor alfa &#40;TNF-&#945;&#41; and C-reactive protein &#40;CRP&#41; levels in all groups&#46; The data are expressed as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation &#40;&#42;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 vs&#46; STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group&#46; One way ANOVA&#44; post hoc Tukey test&#41;&#46;</p>"
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          "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Western blot analysis of Bax and Bcl 2 proteins and mean Bax and Bcl 2 levels in renal tissues of all groups&#46; The data are expressed as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation &#40;&#42;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 vs&#46; STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group&#46; One way ANOVA&#44; post hoc Tukey test&#41;&#46;</p>"
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        "figura" => array:1 [
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          "en" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Mean calcium triphosphatase &#40;Ca<span class="elsevierStyleSup">2&#43;</span>-ATPase&#41; and sodium potassium adenosine triphosphatase &#40;Na<span class="elsevierStyleSup">&#43;</span>&#47;K<span class="elsevierStyleSup">&#43;</span>-ATPase&#41; enzyme activities in all groups&#46; The data are expressed as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation &#40;&#42;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 vs&#46; STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI group&#46; One way ANOVA&#44; post hoc Tukey test&#41;&#46;</p>"
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      8 => array:8 [
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          "leyenda" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">The data are expressed median&#44; minimum and maximum using non-parametric Kruskal&#8211;Wallis test&#46; <span class="elsevierStyleItalic">p</span> value<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 was considered significant&#46; All results belong to STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI compared to the other groups&#44; and <span class="elsevierStyleItalic">p</span> values were represented in the columns&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Left kidney&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t" scope="col">Pathological alterations&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " colspan="2" align="center" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">STZ &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#41;</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#41;</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">1</span> &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#41;</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">2</span> &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#41;</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">3</span> &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#41;</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Minimum to maximum &#40;median&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Minimum to maximum &#40;median&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Minimum to maximum &#40;median&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Minimum to maximum &#40;median&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Minimum to maximum &#40;median&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Proximal tubular damage</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Proximal tubular dilation and atrophy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#8211;2 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;007 &#40;<span class="elsevierStyleItalic">U</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;00&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#8211;3 &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#8211;3 &#40;2&#46;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;0&#46;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">1&#8211;2 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;004 &#40;<span class="elsevierStyleItalic">U</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;00&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#8211;2 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;004 &#40;<span class="elsevierStyleItalic">U</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;00&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Loss of brush border&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#8211;1 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&#46;003 &#40;<span class="elsevierStyleItalic">U</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;00&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#8211;4 &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#8211;2 &#40;1&#46;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;011 &#40;<span class="elsevierStyleItalic">U</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#46;00&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#8211;1 &#40;0&#46;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#8211;1 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;003 &#40;<span class="elsevierStyleItalic">U</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;00&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Proximal tubular necrosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#8211;2 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&#46;004 &#40;<span class="elsevierStyleItalic">U</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#8211;4 &#40;3&#46;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#8211;3 &#40;2&#46;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;0&#46;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#8211;2 &#40;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;007 &#40;<span class="elsevierStyleItalic">U</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;00&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#8211;2 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;004 &#40;<span class="elsevierStyleItalic">U</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="12" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Distal tubular damage</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Distal tubular dilation and atrophy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#8211;2 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;008 &#40;<span class="elsevierStyleItalic">U</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;00&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#8211;4 &#40;3&#46;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#8211;4 &#40;2&#46;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;0&#46;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#8211;2 &#40;1&#46;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;012 &#40;<span class="elsevierStyleItalic">U</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#46;00&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#8211;2 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;004 &#40;<span class="elsevierStyleItalic">U</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;00&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Distal tubular necrosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#8211;2 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;005 &#40;<span class="elsevierStyleItalic">U</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;00&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#8211;4 &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#8211;3 &#40;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;0&#46;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#8211;3 &#40;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;0&#46;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#8211;2 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;008 &#40;<span class="elsevierStyleItalic">U</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;00&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="12" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Glomerular damage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Glomerular basement membrane thickening&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#8211;1 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;027 &#40;<span class="elsevierStyleItalic">U</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5&#46;00&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#8211;2 &#40;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#8211;2 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;0&#46;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#8211;1 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;014 &#40;<span class="elsevierStyleItalic">U</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#46;00&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#8211;1 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;014 &#40;<span class="elsevierStyleItalic">U</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#46;00&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="12" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tubulointerstital damage</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Interstitial fibrosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#8211;1 &#40;0&#46;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;0&#46;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#8211;1 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">0&#8211;2 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">&#62;0&#46;05&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#8211;1 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">&#62;0&#46;05&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#8211;3 &#40;0&#46;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">&#62;0&#46;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hemorrhage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#8211;3 &#40;1&#46;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;005 &#40;<span class="elsevierStyleItalic">U</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;00&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">3&#8211;4 &#40;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#8211;4 &#40;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;029 &#40;<span class="elsevierStyleItalic">U</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5&#46;00&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#8211;1 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;003 &#40;<span class="elsevierStyleItalic">U</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;00&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&#8211;2 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;003 &#40;<span class="elsevierStyleItalic">U</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;00&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mononuclear cell infiltration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#8211;2 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;008 &#40;<span class="elsevierStyleItalic">U</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;00&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">2&#8211;4 &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#8211;3 &#40;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;008 &#40;<span class="elsevierStyleItalic">U</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;00&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#8211;2 &#40;0&#46;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;006 &#40;<span class="elsevierStyleItalic">U</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;00&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#8211;1 &#40;0&#46;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;003 &#40;<span class="elsevierStyleItalic">U</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;00&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="12" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vascular damage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Glomerulointerstitial congestion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#8211;3 &#40;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;020 &#40;<span class="elsevierStyleItalic">U</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#46;00&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#8211;4 &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#8211;3 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;014 &#40;<span class="elsevierStyleItalic">U</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#46;00&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#8211;2 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;004 &#40;<span class="elsevierStyleItalic">U</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">0&#46;003 &#40;<span class="elsevierStyleItalic">U</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;00&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Total damage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;004 &#40;<span class="elsevierStyleItalic">U</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;00&#41;&nbsp;\t\t\t\t\t\t\n
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                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2148166.png"
              ]
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          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Summary statistics and Mann Whitney U test results about histopathological scores in the all groups&#46;</p>"
        ]
      ]
      9 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table "
            "rol" => "short"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">The data are expressed as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation&#46; <span class="elsevierStyleItalic">p</span> value<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 was considered significant&#46; All results belong to STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI compared to the other groups&#44; and <span class="elsevierStyleItalic">p</span> values were represented in the columns&#46;</p>"
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t" scope="col">Biochemical parameters&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">STZ &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#41;</th><th class="td" title="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#41;</th><th class="td" title="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">1</span> &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#41;</th><th class="td" title="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">2</span> &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#41;</th><th class="td" title="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">STZ<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IRI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BRB<span class="elsevierStyleInf">3</span> &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#41;</th></tr><tr title="table-row"><th class="td" title="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> value&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> value&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> value&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> value&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> value&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Blood urea nitrogen &#40;BUN&#41; &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">37&#46;19<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;79&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">120&#46;32<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;98&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">114&#46;29<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;55&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;002&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">95&#46;37<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">88&#46;96<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Creatinine &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">1&#46;98<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;08&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;31<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">5&#46;17<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;0&#46;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;68<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;00<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;09&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Total antioxidant capacity &#40;TAS&#41; &#40;mmol Trolox equiv&#46;&#47;l&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;84<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;06&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;21<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;36<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;06&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;55<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;73<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Total oxidant status &#40;TOS&#41; &#40;&#956;mol H<span class="elsevierStyleInf">2</span>O<span class="elsevierStyleInf">2</span> Trolox equiv&#46;&#47;l&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#46;83<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#46;08<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#46;18<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#46;39<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#46;17<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Oxidative stress index &#40;OSI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>TOS&#47;TAS&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;93<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;09&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#46;86<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;25<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;36<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;05<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tumor necrosis factor alpha &#40;TNF-&#945;&#41; &#40;pg&#47;ml&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">638&#46;98<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&#46;82&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1108&#46;38<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>46&#46;02&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1011&#46;43<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>46&#46;28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;008&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">918&#46;44<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>19&#46;62&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">895&#46;96<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>68&#46;23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C-reactive protein &#40;CRP&#41; &#40;ng&#47;ml&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;28<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#46;93<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;14<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;34<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;91<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lactate dehydrogenase &#40;LDH&#41; &#40;mU&#47;ml&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#46;99<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&#46;28<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
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                            3 => "N&#46; Boztas"
                            4 => "M&#46; Ozbilgin"
                            5 => "B&#46;U&#46; Ergur"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Biomed Res Int"
                        "fecha" => "2016"
                        "volumen" => "2016"
                        "paginaInicial" => "1"
                        "paginaFinal" => "9"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0275"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Thymoquinone improves the kidney and liver changes induced by chronic cyclosporine A treatment and acute renal ischaemia&#47;reperfusion in rats"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46;M&#46; Farag"
                            1 => "G&#46;O&#46; Ahmed"
                            2 => "R&#46;R&#46; Shehata"
                            3 => "A&#46;H&#46; Kazem"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/jphp.12363"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Pharm Pharmacol"
                        "fecha" => "2015"
                        "volumen" => "67"
                        "paginaInicial" => "731"
                        "paginaFinal" => "739"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25644194"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0280"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Ischemia causes rapidly progressive nephropathy in the diabetic rat"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "J&#46; Melin"
                            1 => "O&#46; Hellberg"
                            2 => "L&#46;M&#46; Akyurek"
                            3 => "O&#46; Kallskog"
                            4 => "E&#46; Larsson"
                            5 => "B&#46;C&#46; Fellstr&#246;m"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ki.1997.420"
                      "Revista" => array:6 [
                        "tituloSerie" => "Kidney Int"
                        "fecha" => "1997"
                        "volumen" => "52"
                        "paginaInicial" => "985"
                        "paginaFinal" => "991"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9328937"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0285"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Renal ischemia&#47;reperfusion injury&#59; from pathophysiology to treatment"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "M&#46; Malek"
                            1 => "M&#46; Nematbakhsh"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.12861/jrip.2015.06"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Renal Inj Prev"
                        "fecha" => "2015"
                        "volumen" => "4"
                        "paginaInicial" => "20"
                        "paginaFinal" => "27"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26060833"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0290"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Delayed recovery of renal regional blood flow in diabetic mice"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "H&#46; Shi"
                            1 => "D&#46; Patschan"
                            2 => "T&#46; Epstein"
                            3 => "M&#46;S&#46; Goligorsky"
                            4 => "J&#46; Winaver"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1152/ajprenal.00215.2007"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Physiol Renal Physiol"
                        "fecha" => "2007"
                        "volumen" => "293"
                        "paginaInicial" => "F1512"
                        "paginaFinal" => "F1517"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17881464"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0295"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Acute renal failure in patients with type 1 diabetes mellitus"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "G&#46; Woodrow"
                            1 => "A&#46;M&#46; Brownjohn"
                            2 => "J&#46;H&#46; Turney"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/pgmj.70.821.192"
                      "Revista" => array:6 [
                        "tituloSerie" => "Postgrad Med J"
                        "fecha" => "1994"
                        "volumen" => "70"
                        "paginaInicial" => "192"
                        "paginaFinal" => "194"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8183751"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0300"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hyperglycaemia and renal ischaemia&#8211;reperfusion injury"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "J&#46; Melin"
                            1 => "O&#46; Hellberg"
                            2 => "B&#46; Fellstr&#246;m"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/ndt/18.3.460"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nephrol Dial Transplant"
                        "fecha" => "2003"
                        "volumen" => "18"
                        "paginaInicial" => "460"
                        "paginaFinal" => "462"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12584261"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0305"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "The effects of Berberis vulgaris fruit extract on serum lipoproteins&#44; apoB&#44; apoA-I&#44; homocysteine&#44; glycemic control and total antioxidant capacity in type 2 diabetic patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "F&#46; Shidfar"
                            1 => "S&#46;S&#46; Ebrahimi"
                            2 => "S&#46; Hosseini"
                            3 => "I&#46; Heydari"
                            4 => "S&#46; Shidfar"
                            5 => "G&#46; Hajhassani"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Iran J Pharm Res"
                        "fecha" => "2012"
                        "volumen" => "11"
                        "paginaInicial" => "643"
                        "paginaFinal" => "652"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24250489"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0310"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Berberine improves mesenteric artery insulin sensitivity through up-regulating insulin receptor-mediated signaling in diabetic rats"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46;H&#46; Geng"
                            1 => "G&#46;H&#46; Li"
                            2 => "X&#46; Zhang"
                            3 => "P&#46; Zhang"
                            4 => "M&#46;Q&#46; Dong"
                            5 => "Z&#46;J&#46; Zhao"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/bph.13466"
                      "Revista" => array:6 [
                        "tituloSerie" => "Br J Pharmacol"
                        "fecha" => "2016"
                        "volumen" => "173"
                        "paginaInicial" => "1569"
                        "paginaFinal" => "1579"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26914282"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0315"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antioxidant and anti-inflammatory activities of berberine in the treatment of diabetes mellitus"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "Z&#46; Li"
                            1 => "Y&#46;N&#46; Geng"
                            2 => "J&#46;D&#46; Jiang"
                            3 => "W&#46;J&#46; Kong"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1155/2014/289264"
                      "Revista" => array:5 [
                        "tituloSerie" => "Evid Based Complement Alternat Med"
                        "fecha" => "2014"
                        "volumen" => "2014"
                        "paginaInicial" => "289264"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24669227"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0320"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Berberine inhibits enterovirus 71 replication by downregulating the MEK&#47;ERK signaling pathway autophagy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "H&#46; Wang"
                            1 => "K&#46; Li"
                            2 => "L&#46; Ma"
                            3 => "S&#46; Wu"
                            4 => "J&#46; Hu"
                            5 => "H&#46; Yan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/1743-422X-4-1"
                      "Revista" => array:6 [
                        "tituloSerie" => "Virol J"
                        "fecha" => "2017"
                        "volumen" => "4"
                        "paginaInicial" => "1"
                        "paginaFinal" => "8"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17204159"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0325"
              "etiqueta" => "15"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inhibition of oral streptococci growth induced by the complementary action of berberine chloride and antibacterial compounds"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "A&#46; Dziedzic"
                            1 => "R&#46;D&#46; Wojtyczka"
                            2 => "R&#46; Kubina"
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                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Molecules"
                        "fecha" => "2015"
                        "volumen" => "20"
                        "paginaInicial" => "13705"
                        "paginaFinal" => "13724"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0330"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neuroprotective effect of ischemic preconditioning via modulating the expression of cerebral miRNAs against transient cerebral ischemia in diabetic rats"
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                          "etal" => false
                          "autores" => array:4 [
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                            1 => "M&#46;O&#46; Altintas"
                            2 => "M&#46; Kumas"
                            3 => "T&#46; Asil"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1080/01616412.2016.1232013"
                      "Revista" => array:6 [
                        "tituloSerie" => "Neurol Res"
                        "fecha" => "2016"
                        "volumen" => "38"
                        "paginaInicial" => "1003"
                        "paginaFinal" => "1011"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27635859"
                            "web" => "Medline"
                          ]
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                      ]
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              "identificador" => "bib0335"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Protective role of recombinant human erythropoietin in kidney and lung injury following renal bilateral ischemia&#8211;reperfusion in rat model"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Moeini"
                            1 => "M&#46; Nematbakhsh"
                            2 => "M&#46; Fazilati"
                            3 => "A&#46; Talebi"
                            4 => "A&#46;A&#46; Pilehvarian"
                            5 => "F&#46; Azarkish"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Prev Med"
                        "fecha" => "2013"
                        "volumen" => "4"
                        "paginaInicial" => "648"
                        "paginaFinal" => "655"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23930182"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0340"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A new automated colorimetric method for measuring total oxidant status"
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                          "etal" => false
                          "autores" => array:1 [
                            0 => "O&#46; Erel"
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                        ]
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                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.clinbiochem.2005.08.008"
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                        "tituloSerie" => "Clin Biochem"
                        "fecha" => "2005"
                        "volumen" => "38"
                        "paginaInicial" => "1103"
                        "paginaFinal" => "1111"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16214125"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0345"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Analysis of the diagnostic efficiency of serum oxidative stress parameters in patients with breast cancer at various clinical stages"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;F&#46; Feng"
                            1 => "L&#46; Lu"
                            2 => "C&#46;M&#46; Dai"
                            3 => "D&#46; Wang"
                            4 => "Y&#46;H&#46; Yang"
                            5 => "Y&#46;W&#46; Yang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.clinbiochem.2016.02.005"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Biochem"
                        "fecha" => "2016"
                        "volumen" => "49"
                        "paginaInicial" => "692"
                        "paginaFinal" => "698"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26899366"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0350"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A novel automated direct measurement method for total antioxidant capacity using a new generation&#44; more stable ABTS radical cation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
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                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.clinbiochem.2003.11.015"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Biochem"
                        "fecha" => "2004"
                        "volumen" => "37"
                        "paginaInicial" => "277"
                        "paginaFinal" => "285"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15003729"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0355"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The Madrid Acute Renal Failure Group&#46; Epidemiology of acute renal failure&#58; a prospective multicenter community based study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "F&#46; Lia&#241;o"
                            1 => "J&#46; Pascual"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ki.1996.380"
                      "Revista" => array:6 [
                        "tituloSerie" => "Kidney Int"
                        "fecha" => "1996"
                        "volumen" => "50"
                        "paginaInicial" => "811"
                        "paginaFinal" => "818"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8872955"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0360"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inflammatory cells in ischemic acute renal failure"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "J&#46;J&#46; Friedewald"
                            1 => "H&#46; Rabb"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1523-1755.2004.761_3.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Kidney Int"
                        "fecha" => "2004"
                        "volumen" => "66"
                        "paginaInicial" => "486"
                        "paginaFinal" => "490"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15253694"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0365"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Animal models of kidney inflammation in translational medicine"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46; Holderied"
                            1 => "N&#46;H&#46; Andersen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Drug Discov Today Dis Model"
                        "fecha" => "2014"
                        "volumen" => "11"
                        "paginaInicial" => "19"
                        "paginaFinal" => "27"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0370"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Ischemic acute renal failure&#58; an inflammatory disease&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "J&#46;V&#46; Bonventre"
                            1 => "A&#46; Zuk"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1523-1755.2004.761_2.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Kidney Int"
                        "fecha" => "2004"
                        "volumen" => "66"
                        "paginaInicial" => "480"
                        "paginaFinal" => "485"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15253693"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0375"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cellular pathophysiology of ischemic acute kidney injury"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "J&#46;V&#46; Bonventre"
                            1 => "L&#46; Yang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1172/JCI45161"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Invest"
                        "fecha" => "2011"
                        "volumen" => "121"
                        "paginaInicial" => "4210"
                        "paginaFinal" => "4221"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22045571"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0380"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Treatment of acute renal failure"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "R&#46;A&#46; Star"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1046/j.1523-1755.1998.00210.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Kidney Int"
                        "fecha" => "1998"
                        "volumen" => "54"
                        "paginaInicial" => "1817"
                        "paginaFinal" => "1831"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9853246"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0385"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Renal ischemia&#47;reperfusion injury&#58; functional tissue preservation by anti-activated 1 integrin therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Molina"
                            1 => "M&#46; Ubeda"
                            2 => "M&#46;M&#46; Escribese"
                            3 => "L&#46; Garc&#237;a-Bermejo"
                            4 => "D&#46; Sancho"
                            5 => "G&#46; P&#233;rez de Lema"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1681/ASN.2004070528"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Soc Nephrol"
                        "fecha" => "2005"
                        "volumen" => "16"
                        "paginaInicial" => "374"
                        "paginaFinal" => "382"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15590758"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0390"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Renoprotective effect of berberine via intonation on apoptosis and mitochondrial-dependent pathway in renal ischemia reperfusion-induced mutilation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "A&#46; Visnagri"
                            1 => "A&#46;D&#46; Kandhare"
                            2 => "S&#46;L&#46; Bodhankar"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Ren Fail"
                        "fecha" => "2015"
                        "volumen" => "7"
                        "paginaInicial" => "482"
                        "paginaFinal" => "493"
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0395"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lycopene has reduced renal damage histopathologically and biochemically in experimental renal ischemia&#8211;reperfusion injury"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46; Kaya"
                            1 => "R&#46; Karabulut"
                            2 => "Z&#46; Turkyilmaz"
                            3 => "K&#46; Sonmez"
                            4 => "G&#46; Kulduk"
                            5 => "&#214;&#46; G&#252;lbahar"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3109/0886022X.2015.1064742"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ren Fail"
                        "fecha" => "2015"
                        "volumen" => "37"
                        "paginaInicial" => "1390"
                        "paginaFinal" => "1395"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26161692"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0400"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hyperglycemia increases susceptibility to ischemic necrosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "D&#46; L&#233;vigne"
                            1 => "M&#46; Tobalem"
                            2 => "A&#46; Modarressi"
                            3 => "B&#46; Pittet-Cu&#233;nod"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Biomed Res Int"
                        "fecha" => "2013"
                        "volumen" => "2013"
                        "paginaInicial" => "1"
                        "paginaFinal" => "5"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0405"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neuroprotective effect of ischemic preconditioning via modulating the expression of adropin and oxidative markers against transient cerebral ischemia in diabetic rats"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "O&#46; Altintas"
                            1 => "M&#46; Kumas"
                            2 => "M&#46;O&#46; Altintas"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.peptides.2016.03.011"
                      "Revista" => array:6 [
                        "tituloSerie" => "Peptides"
                        "fecha" => "2016"
                        "volumen" => "79"
                        "paginaInicial" => "31"
                        "paginaFinal" => "38"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27020247"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0410"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vascularization pattern after ischemic stroke is different in control versus diabetic rats&#58; relevance to stroke recovery"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "R&#46; Prakash"
                            1 => "W&#46; Li"
                            2 => "Z&#46; Qu"
                            3 => "M&#46;A&#46; Johnson"
                            4 => "S&#46;C&#46; Fagan"
                            5 => "A&#46; Ergul"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1161/STROKEAHA.113.001660"
                      "Revista" => array:6 [
                        "tituloSerie" => "Stroke"
                        "fecha" => "2013"
                        "volumen" => "44"
                        "paginaInicial" => "2875"
                        "paginaFinal" => "2882"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23920018"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0415"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antioxidant capacity after acute ischaemic stroke"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "S&#46;E&#46; Gariballa"
                            1 => "T&#46;P&#46; Hutchin"
                            2 => "A&#46;J&#46; Sinclair"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/qjmed/95.10.685"
                      "Revista" => array:6 [
                        "tituloSerie" => "QJM"
                        "fecha" => "2002"
                        "volumen" => "95"
                        "paginaInicial" => "685"
                        "paginaFinal" => "690"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12324641"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0420"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Glomerular and proximal tubular morphology after single nephron obstruction"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "G&#46;A&#46; Tanner"
                            1 => "A&#46;P&#46; Evan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ki.1989.300"
                      "Revista" => array:6 [
                        "tituloSerie" => "Kidney Int"
                        "fecha" => "1989"
                        "volumen" => "36"
                        "paginaInicial" => "1050"
                        "paginaFinal" => "1060"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2601255"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0425"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Update on Mechanisms of ischemic acute kidney injury"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "P&#46; Devarajan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1681/ASN.2006010017"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Soc Nephrol"
                        "fecha" => "2006"
                        "volumen" => "17"
                        "paginaInicial" => "1503"
                        "paginaFinal" => "1520"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16707563"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib0430"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Detection of necrosis by release of lactate dehydrogenase activity"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "F&#46;K&#46; Chan"
                            1 => "K&#46; Moriwaki"
                            2 => "M&#46;J&#46; De Rosa"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/978-1-62703-290-2_7"
                      "Revista" => array:6 [
                        "tituloSerie" => "Methods Mol Biol"
                        "fecha" => "2013"
                        "volumen" => "979"
                        "paginaInicial" => "65"
                        "paginaFinal" => "70"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23397389"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0435"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Renal cortical lactate dehydrogenase&#58; a useful&#44; accurate&#44; quantitative marker of in vivo tubular injury and acute renal failure"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "R&#46;A&#46; Zager"
                            1 => "A&#46;C&#46; Johnson"
                            2 => "K&#46; Becker"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "PLoS One"
                        "fecha" => "2013"
                        "volumen" => "8"
                        "paginaInicial" => "1"
                        "paginaFinal" => "8"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib0440"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Modulation of C-reactive protein&#44; tumor necrosis factor-alpha&#44; and adiponectin by diet&#44; exercise&#44; and weight loss"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "M&#46;J&#46; Puglisi"
                            1 => "M&#46;L&#46; Fernandez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3945/jn.108.097188"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Nutr"
                        "fecha" => "2008"
                        "volumen" => "138"
                        "paginaInicial" => "2293"
                        "paginaFinal" => "2296"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19022947"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib0445"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tumor necrosis factor &#40;TNF-alpha&#41; and C-reactive protein &#40;CRP&#41; are positively associated with the risk of chronic kidney disease in patients with type 2 diabetes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
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                            1 => "J&#46;Y&#46; Hwang"
                            2 => "J&#46;E&#46; Park"
                            3 => "Y&#46;J&#46; Choi"
                            4 => "K&#46;B&#46; Huh"
                            5 => "W&#46;Y&#46; Kim"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
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                        "tituloSerie" => "Yonsei Med J"
                        "fecha" => "2010"
                        "volumen" => "51"
                        "paginaInicial" => "519"
                        "paginaFinal" => "525"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20499416"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib0450"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Berberine improves glucose homeostasis in streptozotocin-induced diabetic rats in association with multiple factors of insulin resistance"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
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                            1 => "Y&#46; Wang"
                            2 => "J&#46; Zhang"
                            3 => "C&#46; Sun"
                            4 => "A&#46; Lopez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "ISRN Endocrinol"
                        "fecha" => "2011"
                        "volumen" => "2011"
                        "paginaInicial" => "1"
                        "paginaFinal" => "8"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib0455"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Berberine reduces the expression of adipogenic enzymes and inflammatory molecules of 3T3-L1 adipocyte"
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                          "etal" => true
                          "autores" => array:6 [
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                            1 => "I&#46;S&#46; Ahn"
                            2 => "Y&#46;H&#46; Kim"
                            3 => "J&#46;W&#46; Park"
                            4 => "S&#46;Y&#46; Lee"
                            5 => "C&#46;K&#46; Hyun"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/emm.2006.71"
                      "Revista" => array:6 [
                        "tituloSerie" => "Exp Mol Med"
                        "fecha" => "2006"
                        "volumen" => "38"
                        "paginaInicial" => "599"
                        "paginaFinal" => "605"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17202835"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib0460"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Protective effect of ischemic preconditioning on myocardium against remote tissue injury following transient focal cerebral ischemia in diabetic rats"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
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                            1 => "O&#46; Altintas"
                            2 => "E&#46; Karatas"
                            3 => "A&#46; Kocyigit"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.5935/abc.20170164"
                      "Revista" => array:7 [
                        "tituloSerie" => "Arq Bras Cardiol"
                        "fecha" => "2017"
                        "volumen" => "109"
                        "paginaInicial" => "516"
                        "paginaFinal" => "526"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29160389"
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                    0 => array:2 [
                      "titulo" => "Hypoxia leads to Na&#44; K-ATPase downregulation via Ca<span class="elsevierStyleSup">2&#43;</span> release-activated Ca<span class="elsevierStyleSup">2&#43;</span> channels and AMPK activation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46;A&#46; Gusarova"
                            1 => "H&#46;E&#46; Trejo"
                            2 => "L&#46;A&#46; Dada"
                            3 => "A&#46; Briva"
                            4 => "L&#46;C&#46; Welch"
                            5 => "R&#46;B&#46; Hamanaka"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1128/MCB.05114-11"
                      "Revista" => array:6 [
                        "tituloSerie" => "Mol Cell Biol"
                        "fecha" => "2011"
                        "volumen" => "31"
                        "paginaInicial" => "3546"
                        "paginaFinal" => "3556"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21730292"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib0470"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Plasma membrane and sarcoplasmic reticulum Ca-ATPase and smooth muscle"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "J&#46;M&#46; Gonzalez"
                            1 => "L&#46;J&#46; Jost"
                            2 => "D&#46; Rouse"
                            3 => "W&#46;N&#46; Suki"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Miner Electrolyte Metab"
                        "fecha" => "1996"
                        "volumen" => "22"
                        "paginaInicial" => "345"
                        "paginaFinal" => "348"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8933505"
                            "web" => "Medline"
                          ]
                        ]
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                  ]
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              ]
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            44 => array:3 [
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              "etiqueta" => "45"
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                    0 => array:2 [
                      "titulo" => "Evidence that BCL-2 represses apoptosis by regulating endoplasmic reticulum-associated Ca<span class="elsevierStyleSup">2&#43;</span> fluxes"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "M&#46; Lam"
                            1 => "G&#46; Dubyak"
                            2 => "L&#46; Chen"
                            3 => "G&#46; Nu&#241;ez"
                            4 => "R&#46;L&#46; Miesfeld"
                            5 => "C&#46;W&#46; Distelhorst"
                          ]
                        ]
                      ]
                    ]
                  ]
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                    0 => array:2 [
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                        "tituloSerie" => "Proc Natl Acad Sci USA"
                        "fecha" => "1994"
                        "volumen" => "91"
                        "paginaInicial" => "6569"
                        "paginaFinal" => "6573"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8022822"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0480"
              "etiqueta" => "46"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The Na&#44;K-ATPase"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "J&#46;C&#46; Skou"
                            1 => "M&#46; Esmann"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/bf00768846"
                      "Revista" => array:6 [
                        "tituloSerie" => "J&#46; Bioenerg Biomembr"
                        "fecha" => "1992"
                        "volumen" => "24"
                        "paginaInicial" => "249"
                        "paginaFinal" => "261"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1328174"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "etiqueta" => "47"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Down-regulated Na<span class="elsevierStyleSup">&#40;&#43;&#41;</span>&#47;K<span class="elsevierStyleSup">&#40;&#43;&#41;</span>-ATPase activity in ischemic penumbra after focal cerebral ischemia&#47;reperfusion in rats"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "H&#46; Huang"
                            1 => "Y&#46;M&#46; Chen"
                            2 => "F&#46; Zhu"
                            3 => "S&#46;T&#46; Tang"
                            4 => "J&#46;D&#46; Xiao"
                            5 => "L&#46;L&#46; Li"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Clin Exp Pathol"
                        "fecha" => "2015"
                        "volumen" => "8"
                        "paginaInicial" => "12708"
                        "paginaFinal" => "12717"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26722460"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "etiqueta" => "48"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Modulation of cardiac Na<span class="elsevierStyleSup">&#43;</span>&#44;K<span class="elsevierStyleSup">&#43;</span>-ATPase cell surface abundance by simulated ischemia&#8211;reperfusion and ouabain preconditioning"
                      "autores" => array:1 [
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                          "etal" => false
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                            1 => "Y&#46; Sottejeau"
                            2 => "Q&#46; Duan"
                            3 => "J&#46;L&#46; Karabin"
                            4 => "S&#46;V&#46; Pierre"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1152/ajpheart.00374.2012"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Physiol Heart Circ Physiol"
                        "fecha" => "2013"
                        "volumen" => "304"
                        "paginaInicial" => "H94"
                        "paginaFinal" => "H103"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23086991"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "etiqueta" => "49"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Folic acid can contribute to memory deficit and Na<span class="elsevierStyleSup">&#43;</span>&#44; K<span class="elsevierStyleSup">&#43;</span>-ATPase failure in the hippocampus of adolescent rats submitted to hypoxia-ischemia"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;V&#46; Carletti"
                            1 => "B&#46;F&#46; Deniz"
                            2 => "J&#46;J&#46; Rojas"
                            3 => "P&#46;M&#46; Miguel"
                            4 => "J&#46; Kolling"
                            5 => "E&#46;B&#46; Scherer"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "CNS Neurol Disord Drug Targets"
                        "fecha" => "2016"
                        "volumen" => "15"
                        "paginaInicial" => "64"
                        "paginaFinal" => "72"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26553162"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            49 => array:3 [
              "identificador" => "bib0500"
              "etiqueta" => "50"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effects of FDP and Danshen on renal cortical Na-K-ATPase activity in rats after treatment with renal ischemia and gentamicin"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "F&#46;M&#46; Lu"
                            1 => "S&#46;Y&#46; Lin"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Chin Med J"
                        "fecha" => "1989"
                        "volumen" => "102"
                        "paginaInicial" => "516"
                        "paginaFinal" => "523"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2560955"
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                          ]
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                      ]
                    ]
                  ]
                ]
              ]
            ]
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Información del artículo

ISSN: 02116995
Idioma original: Inglés

DOI:10.1016/j.nefro.2018.10.006

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