title: Hesperidin blunts streptozotocin-isoproternol induced myocardial toxicity in rats by altering of PPAR-γ receptor.
abstract: Hesperidin has been shown to possess cardioprotective and anti-diabetic potential. Hitherto, its molecular mechanism on isoproterenol (ISO)-induced myocardial dysfunction in diabetes is still not explored. Hence, for the first time we sought to investigate whether hesperidin exerts any beneficial effect on the pathophysiology of myocardial infarction (MI) in diabetes through the PPAR-γ pathway by assessing a variety of indices e.g., apoptosis, hemodynamic, biochemical and histoarchitectural changes. Diabetes was induced by a single dose of STZ (50 mg/kg IP). Diabetic rats received either hesperidin (100 mg/kg/day orally), the PPAR-γ antagonist GW9662 (1 mg/kg/day IP), or both for 14 days with concurrent administration of ISO (85 mg/kg SC) on days 13 and 14. ISO-STZ rats resulted in severe myocardial dysfunction (decreased ±LVdP/dt and increased LVEDP). In addition, augmented myocardial thiobarbituric acid-reactive substances and serum troponin-I with a concomitant decrease in level of glutathione and activities of catalase, superoxide dismutase antioxidants with cardiac injury biomarkers creatine kinase-MB isoenzyme, lactate dehydrogenase were seen. Morphological studies of the ISO-STZ challenged myocardium exhibited severe necrosis, edema and inflammatory changes. In Western blot analysis, Bcl-2 and PPAR-γ expression were decreased where as Bax expression was significantly increased, suggesting role of apoptosis in myocardial dysfunction. Interestingly, hesperidin treatment positively modulated these parameters as validated by improved hemodynamic and left ventricular functions, fortified endogenous anti-oxidant defence system and improved structural integrity of the myocardium. However, significant effects were lowered in animals treated with hesperidin plus GW9662. Moreover, down-regulated PPAR-γ and Bcl-2 expressions in myocardial infarcted diabetic hearts were increased by hesperidin treatment. Hence, for the first time the present study suggests that, hesperidin reduces oxidative stress, apoptosis and improves cardiac function via the PPAR-γ pathway.
authors: School of Pharmaceutical Sciences, Jaipur National University, Jagatpura, Jaipur 302017, India; Department of Pharmacology, All India Institute of Medical Sciences, New Delhi 110029, India; Department of Pharmacology, R.C. Patel Institute of Pharmaceutical Education and Research, Shirpur 425405, Maharashtra, India.
authors: Yogeeta O
authors: YO
authors: Agrawal
authors: School of Pharmaceutical Sciences, Jaipur National University, Jagatpura, Jaipur 302017, India.
authors: Pankaj Kumar
authors: PK
authors: Sharma
authors: School of Pharmaceutical Sciences, Jaipur National University, Jagatpura, Jaipur 302017, India.
authors: Birendra
authors: B
authors: Shrivastava
authors: Department of Pharmacology, All India Institute of Medical Sciences, New Delhi 110029, India.
authors: Dharamvir Singh
authors: DS
authors: Arya
authors: Department of Pharmacology, R.C. Patel Institute of Pharmaceutical Education and Research, Shirpur 425405, Maharashtra, India. Electronic address: goyal.aiims@gmail.com.
authors: Sameer N
authors: SN
authors: Goyal
mesh_terms: D000813:Anilides / Q000494:pharmacology*; D000818:Animals; D002374:Catalase / Q000097:blood; D052279:Creatine Kinase, MB Form / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000097:blood; D006569:Hesperidin / Q000494:pharmacology*; D007545:Isoproterenol / Q000008:administration & dosage*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D046529:Microscopy, Electron, Transmission; D009203:Myocardial Infarction / Q000139:chemically induced* / Q000378:metabolism; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011897:Random Allocation; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000097:blood; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D019210:Troponin I / Q000097:blood
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D047495:PPAR gamma; D017392:Thiobarbituric Acid Reactive Substances; D019210:Troponin I; D006569:Hesperidin; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D013482:Superoxide Dismutase; D052279:Creatine Kinase, MB Form; D005978:Glutathione; D007545:Isoproterenol
keywords: Apoptosis; Bioflavonoid; Cardiotoxicity; Isoproterenol; Myocardial infarction; PPAR