Pyruvate attenuates cardiac dysfunction and oxidative stress in isoproterenol-induced cardiotoxicity.
Pyruvate, a potent endogenous antioxidant and an important metabolic fuel is essential for the cardiac function and tissue defense mechanism. The present study was evaluated to investigate whether pyruvate attenuates the development of cardiotoxicity in isoproterenol (ISO)-induced myocardial infarction by assessing hemodynamic, biochemical and histopathological parameters. Subcutaneous injection of ISO (85 mg/kg) administered for 2 days at an interval of 24h was used for induction of cardiotoxicity. ISO administration significantly decreased arterial pressure indices, heart rate, contractility {(+)LVdP/dt} and relaxation {(-)LVdP/dt} and increased left ventricular end-diastolic pressure. In addition, a significant reduction in activities of myocardial creatine phosphokinase-MB, lactate dehydrogenase, superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione levels along with increase in thiobarbituric acid reactive substances were also observed following ISO administration. However, pretreatment with pyruvate (0.25, 0.5 and 1.0 g/kg, p.o.) favorably modulated all most every studied parameters in ISO-induced myocardial injury. Furthermore, protective effect of pyruvate was confirmed by histopathological studies. Rats pretreated only with pyruvate did not produce significant change in hemodynamic, biochemical and histopathological parameters. Pyruvate at 0.50 and 1.0 g/kg doses was found to exert optimal cardioprotective effect against ISO-induced myocardial infarction. The results of our study suggest that pyruvate possessing antioxidant activity has a significant cardioprotective effect against ISO-induced myocardial injury.
Cardiovascular Laboratory, Department of Pharmacology, All India Institute of Medical Sciences, New Delhi 29, India. shreeshojha@gmail.com
Shreesh
S
Ojha
Sameer
S
Goyal
Santosh
S
Kumari
Dharamvir Singh
DS
Arya
D000318:Adrenergic beta-Agonists / Q000633:toxicity*; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D007279:Injections, Subcutaneous; D007545:Isoproterenol / Q000633:toxicity*; D008297:Male; D009203:Myocardial Infarction / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D010088:Oxidoreductases; D019289:Pyruvic Acid / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013858:Thiobarbiturates / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D002316:Cardiotonic Agents; D013858:Thiobarbiturates; D019289:Pyruvic Acid; D010088:Oxidoreductases; D007545:Isoproterenol; C029684:thiobarbituric acid