p-Coumaric acid attenuates apoptosis in isoproterenol-induced myocardial infarcted rats by inhibiting oxidative stress
Introduction
According to the world health organization, over 80% of cardiovascular diseases take place in low and middle income countries. Myocardial infarction (MI) is the irreversible necrosis of heart muscle secondary to prolonged ischemia that results from an imbalance between coronary blood supply and myocardial demand. Isoproterenol (ISO), a synthetic catecholamine, causes severe stress in the myocardial tissue and its high dose produces myocardial injury in rats as a result of disturbance in physiological balance between the production of free radicals and antioxidant defense system [1]. It is the acute condition of myocardial necrosis which causes impaired cardiac function, elevated levels of cardiac diagnostic markers, increased lipid peroxidation and decreased antioxidant system [2]. ISO-induced myocardial necrosis involves membrane permeability alterations that bring about the loss of function and integrity of myocardial membranes [3]. MI induced by ISO has been reported to show many morphological and metabolic aberrations in the heart tissue of experimental animals similar to those observed in human MI [4].
Dietary factors play an important role in preventing human diseases. Epidemiological studies have shown that diets rich in herbs, fruits and spices reduce the risk of cardiovascular diseases [5]. p-Coumaric acid is a phenolic acid, widely distributed in plants and form a part of human diet [6]. It is widely present in fruits such as apples, pears and also in vegetables and plant products such as beans, potatoes, tomatoes and tea. Also, p-coumaric acid is abundantly present in pineapple. It has been found to reduce the risk of stomach cancer [7] by reducing the formation of carcinogenic nitrosamines [8].
In the myocardium, apoptosis has been observed in a number of cardiac pathologies including hypoxia, ischemia followed by reperfusion, MI, myocardial hypertrophy and in patients with end-stage heart failure [9]. Evidence has accumulated that oxidative stress activates multiple cell signaling pathways, including the apoptotic pathways [10]. Activation of the apoptotic pathways in the heart may lead to contractile dysfunction prior to cell death. Since apoptosis is implicated in the pathogenesis of MI, the inhibition of apoptosis promises to be a potent target for the treatment of MI. During reperfusion, cardiomyocyte apoptosis occurs at a high rate during a defined time period. Thus, a short-term pretreatment is highly effective. The concept of early therapeutic interference with acute pretreatment to prevent MI and heart failure is extremely attractive. Literature survey has shown that there are no scientific reports available on the effects of p-coumaric acid on apoptosis in MI. Hence, this manuscript addresses the protective effects of p-coumaric acid in ISO induced apoptosis in rats.
Section snippets
Experimental animals
All the experiments were carried out with male albino Wistar rats weighing 170–200 g, obtained from The Central Animal House, Rajah Muthiah Institute of Health Sciences, Annamalai University, Tamil Nadu, India. They were housed in polypropylene cages (47 × 34 × 20 cm) lined with husk, renewed every 24 h under a 12:12 h light/dark cycle at around 22 °C. The rats had free access to tap water and food. The rats were fed on a standard pellet diet (Pranav Agro Industries Ltd., Maharashtra, India). The
Effect of p-coumaric acid on the activity of serum CK-MB (Dose dependent study)
A pilot study was performed with three different doses of p-coumaric acid (2, 4 and 8 mg/kg body weight) to determine the dose dependent effect and the duration of pretreatment of p-coumaric acid in the ISO induced (on 8th and 9th day) myocardial infarcted rats. We examined the activity of cardiac marker enzyme, serum CK-MB in the rats pretreated with p-coumaric acid (2, 4 and 8 mg/kg body weight) in the myocardial infarcted rats. We observed near normalized activity of serum CK-MB when compared
Discussion
A dose dependent study was performed with three different doses of p-coumaric acid (2, 4 and 8 mg/kg body weight) on serum CK-MB activity in the ISO induced myocardial infarcted rats. ISO causes an increase in the activity of diagnostic marker enzyme, CK-MB. The increased activity of CK-MB in serum might be due to ISO-induced myocardial necrosis. Pretreatment with p-coumaric acid (2, 4 and 8 mg/kg body weight) daily for a period of 7 days dose dependently decreased the elevated activity of serum
Conclusions
In conclusion, the biochemical, histological and RT-PCR findings observed from our study indicate that p-coumaric acid offers protection to the myocardium against ISO induced apoptosis in Wistar rats. p-Coumaric acid inhibits oxidative stress, thereby attenuating apoptosis in the myocardial infarcted rats. The observed protective effects of p-coumaric acid could be attributed to antilipid peroxidative, antioxidant and antiapoptotic properties. Thus, the findings of this study may be beneficial
Acknowledgements
The authors are grateful to Dr. C.S. Vijayalakshmi, MD, Consultant Pathologist, Vaishnavi Histopathology and Cytology Centre, Chrompet, Chennai, Tamil Nadu for carrying out the histopathology of heart and its interpretation. We also thank Dr. Philomena Mariadoss, Ph.D., Dean, Madras Medical Mission, College of Health Sciences, Chennai, Tamil Nadu for permitting to perform RT-PCR study in the Department of Genetics.
The authors of this manuscript have certified that they comply with the
References (39)
- et al.
Lipid peroxidation and antioxidant enzymes in isoproterenol induced oxidative stress in rat tissues
Pharmacol Res
(1998) - et al.
Cardioprotective effect of Azadirachta indica A. Juss. on isoprenaline induced myocardial infarction in rats
Int J Cardiol
(2008) - et al.
Isoproterenol-induced myocardial necrosis and membrane permeability alterations in the isolated perfused rabbit heart
Exp Mol Pathol
(1980) - et al.
Dietary intake and bioavailability of polyphenols
J Nutr
(2000) - et al.
Lipid peroxidation measured as thiobarbituric acid reactive substances in tissue slices: characterization and comparison with homogenates and microsomes
Free Radic Biol Med
(1988) - et al.
Ferrous ion oxidation in the presence of xylenol orange for detection of lipid hydroperoxides in low-density lipoprotein
Anal Biochem
(1992) Colorimetric assay of catalase
Anal Biochem
(1972)Tissue sulfhydryl groups
Arch Biochem Biophys
(1959)- et al.
Assays for differentiation of glutathione-S-transferases
Methods Enzymol
(1981) - et al.
Selected methods for the determination of ascorbic acid in animal cells, tissues and fluids
Methods Enzymol
(1979)
Protein measurement with Folin-phenol reagent
J Biol Chem
Effect of aspirin on lipid peroxidation in experimental myocardial infarction in rats
J Nutr Biochem
Superoxide dismutase, reduced glutathione and thiobarbituric acid reactive products in erythrocytes of patients with multiple sclerosis
Int J Biochem
Effect of garlic (Allium sativum) on lipid peroxidation in experimental myocardial infarction in rats
J Ethnopharmacol
Mechanical stress-induced apoptosis in the cardiovascular system
Prog Biophys Mol Biol
Protective role of curcumin against isoproterenol induced myocardial infarction in rats
Mol Cell Biochem
Effect of garlic on cardiovascular disorders: a review
J Nutr
Antioxidant and antigenotoxic effects of plant cell wall hydroxycinnamic acids in cultured HT-29 cells
Mol Nutr Food Res
Reaction of p-hydroxycinnamic acid derivatives with nitrite and its relevance to nitrosamine formation
J Agric Food Chem
Cited by (57)
p-Coumaric acid attenuates the effects of Aβ42 in vitro and in a Drosophila Alzheimer's disease model
2023, Behavioural Brain ResearchThe cardioprotective potentials and the involved mechanisms of phenolic acids in drug-induced cardiotoxicity
2022, European Journal of PharmacologyA pharmacokinetic-pharmacodynamic study to elucidate the cardiovascular protective constituents in Danhong Injection
2022, Journal of Pharmaceutical and Biomedical AnalysisCitation Excerpt :These compounds include salvianolic acid B, rosmarinic acid, p-coumaric acid, salvianolic acid A, danshensu, cytidine, uridine, caffeic acid, protocatechuic acid, and ferulic acid, consistent with previous reports [23–25]. In addition, all the 10 compounds had been reported to possess cardiovascular protective effects [26–32]. Thus, we studied the PK of these compounds in rats plasma to establish the PK-PD correlation.