P442Chrysin alleviates isoproterenol-induced myocardial infarction in diabetic rats through modulation of PPAR-gamma

Abstract

Purpose: Chrysin (5,7-dihydroxylflavone), an agonist of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) has been shown to possess antioxidant and anti-inflammatory properties. Here, we investigated whether chrysin (60 mg/kg/day) can improve the pathophysiology of myocardial infarction in diabetes partially through the PPAR-gamma pathway by assessing a variety of indices, e.g., hemodynamic, biochemical, histoarchitectural changes, and apoptosis. Methods: Diabetes was induced by a single dose of streptozotocin (70 mg/kg, i.p.). Diabetic rats received either chrysin (60 mg/kg/day, orally), PPAR-gamma antagonist GW9662 (1 mg/kg/day, i.p.) or both for 28 days with concurrent administration of isoproterenol (85 mg/kg, SC) on days 27th and 28th. Results: Compared with diabetic controls, diabetic rats with myocardial infarction exhibited altered hemodynamic profiles (MAP, LVEDP, ±LVdP/dtmax) and reduction in the activities of creatine kinase-MB isoenzyme, lactate dehydrogenase, superoxide dismutase, catalase, and glutathione level along with increased level of malondialdehyde. Further, diabetic animals with myocardial infarction exhibited increased myonecrosis, edema, and apoptotic cell death. Treatment with chrysin significantly improved the redox status of the myocardium with subsequent cardiac functional recovery. However, significant effects were lowered in animals treated with chrysin plus GW9662. Chrysin markedly inhibited Bax expression, TUNEL-positive cells, and increased Bcl2 expression. Moreover, down-regulated PPAR-gamma expression in myocardial infarcted diabetic hearts was also increased by chrysin. Conclusion: Chrysin improves myocardial infarction in diabetic rats through a pathway involving PPAR- gamma.