Clinical toxicities of immunosuppressantsNephrotoxicityMagnesium Supplementation Prevents Chronic Cyclosporine Nephrotoxicity via Adjusting Nitric Oxide Synthase Activity
Section snippets
Animal
The present experiments were conducted in accord with the National Institutes of Health Guide for Care and Use of Laboratory Animals. A total of 21 male Wistar rats with body weights between 180 and 220 g were obtained from the Laboratory Animal Center of Hubei Province, China. All rats were allowed free access to standard rat chow for a week. Rats were then housed in a temperature- and light-controlled environment while receiving a semisynthetic low sodium (0.05% sodium) and normal Mg (0.05%
Physiological Study
Physiological parameters are summarized in Table 1. The final body weights of rats in the Mg supplementation group were significantly less than those in the CsA group or the normal control group (CsA + Mg vs CsA, P < .05). On day 28, plasma Mg concentration declined markedly with the duration of CsA treatment (CsA group vs control group, P < .05). Dietary supplementation with Mg attenuated the CsA-induced hypomagnesemia (CsA group vs CsA + Mg group, P < .05).
Plasma creatinine concentration
Discussion
In this study, the histological lesions of chronic cyclosporine nephrotoxicity were observed in rats administered the drug: arteriolopathy, tubular atrophy, tubulointerstitial fibrosis, and thickening of glomerular basement membrane. Oral Mg supplementation markedly attenuated the development of lesions induced by CsA; the Pcr was lower than in the CsA group, strongly suggesting that the renal function deterioration elicited by drug treatment was improved.
NO generated by nNOS within the macula
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Cited by (34)
Can magnesium sulfate prophylaxis reduce colistin nephrotoxicity?
2021, NefrologiaCitation Excerpt :In a study conducted with people who received cisplatin chemotherapy, the supplementation of magnesium to hydration reduced cisplatin nephrotoxicity.18 In another study performed on cyclosporine-treated mice, magnesium supplementation had a renal protective effect by increasing nitric oxide synthase activity in the renal tissue.32 Because there is no study examining the supplementation of Mg with colistin, we referenced other studies for the Mg sulfate doses.
Magnesium Balance in Chronic and End-Stage Kidney Disease
2018, Advances in Chronic Kidney DiseaseCitation Excerpt :There is also increasing evidence that magnesium supplementation can abrogate CNI nephrotoxicity in animal models.69 Various models have shown that magnesium prevents CNI-associated fibrosis, macrophage, and monocyte recruitment and attenuates cyclosporine-induced reduction in kidney nitric oxide production.69-71 The kidneys provide the main route for magnesium excretion, and we have seen how tubular function is responsible for regulating magnesium balance in health and in mild CKD.
Hypomagnesaemia in kidney transplantation
2015, Transplantation ReviewsCitation Excerpt :The anti-oxidant magnesium also blocked the up-regulation of endothelin-1, possibly leading to beneficial effects on glomerular dysfunction [57]. Also, magnesium supplementation attenuated the cyclosporine-induced decrease in renal nitric oxide content versus non-supplemented rats [59]. Magnesium further decreased the activation of the ubiquitous redox-sensitive transcription factor nuclear factor-κB [60], which is up-regulated in rats exposed to cyclosporine in some [58,60], but not all studies [61].
Magnesium-deficiency does not alter calcineurin inhibitors activity in mice
2012, Transplant ImmunologyCitation Excerpt :Hypomagnesemia did not seem to be caused by renal dysfunction or decreased Mg2+ absorption, because it preceded an increase in plasma creatinine level and a decrease in intestinal Mg2+ absorption, and no histological sign of renal injury was observed [32]. Only Mg2+ supplementation supplied as high Mg2+-content diet or Mg2+-enriched drinking water was shown to prevent experimental CsA renal fibrosis [33,34]. Mg2+ is the most abundant intracellular divalent cation and plays an essential role in a wide range of fundamental cellular reactions [35].
The use of cyclosporine in dermatology: Part II
2010, Journal of the American Academy of DermatologyCitation Excerpt :Hypomagnesemia has been reported in 5% to 15% of patients and should be treated with oral magnesium supplements (beginning at 200 mg magnesium daily and increased as needed), with adherence monitored.50 Studies in rats have shown that magnesium supplementation may prevent chronic cyclosporine nephropathy by adjusting nitric oxide synthase activity.154 Hyperuricemia should be treated with a low purine diet and sufficient fluid intake.50
Renal protection with magnesium subcarbonate and magnesium sulphate in patients with epithelial ovarian cancer after cisplatin and paclitaxel chemotherapy: A randomised phase II study
2008, European Journal of CancerCitation Excerpt :Other mechanisms spread to activate mitogen-activated protein kinases, promotion of apoptosis, and stimulation of inflammation and fibrogenesis.22 Yuan and colleagues23 have recently studied the role of magnesium salt supplementation on the development of Cyclosporine A induced nephrotoxicity in rats. Dietary supplementation with magnesium seems to improve renal function and almost abolishes CsA-induced histological lesions via alteration of the abnormal activation of constitutive nitric oxide synthase in this model.
Supported by the Chinese National Basic Research Program (973 Program, No. 2003CB515505).