Cardioprotective effect of pioglitazone in diabetic and non-diabetic rats subjected to acute myocardial infarction involves suppression of AGE-RAGE axis and inhibition of apoptosis.
Insulin resistance increases risk of cardiovascular diseases. This work investigated the protective effect of pioglitazone on myocardial infarction (MI) in non-diabetic and diabetic rats, focusing on its role on advanced glycated endproducts (AGEs) and cardiac apoptotic machinery. Male rats were divided into 2 experiments: experiment I and II (non-diabetic and diabetic rats) were assigned as saline, MI (isoproterenol, 85 mg/kg, daily), and MI+pioglitazone (5, 10, and 20 mg/kg). Injection of isoproterenol in diabetic rats produced greater ECG disturbances compared to non-diabetic rats. Treatment with pioglitazone (5 mg/kg) reduced the infarct size and improved some ECG findings. Pioglitazone (10 mg/kg) enhanced ECG findings, improved the histopathological picture and downregulated apoptosis in cardiac tissues. Whereas the higher dose of pioglitazone (20 mg/kg) did not improve most of the measured parameters but rather worsened some of them, such as proapoptotic markers. Importantly, a positive correlation was found between serum AGEs and cardiac AGE receptors (RAGEs) versus caspase 3 expression in the two experiments. Therefore, the current effect of pioglitazone was, at least in part, mediated through downregulation of AGE-RAGE axis and inhibition of apoptosis. Consequently, these data suggest that pioglitazone, at optimized doses, may have utility in protection from acute MI.
a Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, 41522 Ismailia, Egypt.
Dina M
DM
Khodeer
a Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, 41522 Ismailia, Egypt.
Sawsan A
SA
Zaitone
b Department of Physiology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
Noha E
NE
Farag
a Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, 41522 Ismailia, Egypt.
Yasser M
YM
Moustafa
D000318:Adrenergic beta-Agonists / Q000506:poisoning; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D058065:Diabetic Cardiomyopathies / Q000139:chemically induced / Q000517:prevention & control*; D059305:Diet, High-Fat / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007333:Insulin Resistance; D007545:Isoproterenol / Q000506:poisoning; D008297:Male; D009203:Myocardial Infarction / Q000139:chemically induced / Q000150:complications / Q000517:prevention & control*; D009929:Organ Size / Q000187:drug effects; D050177:Overweight / Q000150:complications / Q000209:etiology / Q000517:prevention & control; D000077205:Pioglitazone; D011897:Random Allocation; D017208:Rats, Wistar; D000067759:Receptor for Advanced Glycation End Products / Q000037:antagonists & inhibitors / Q000378:metabolism; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D000318:Adrenergic beta-Agonists; D002316:Cardiotonic Agents; D017127:Glycation End Products, Advanced; D007004:Hypoglycemic Agents; D000067759:Receptor for Advanced Glycation End Products; D045162:Thiazolidinediones; D007545:Isoproterenol; D000077205:Pioglitazone
advanced glycated end products; apoptose; apoptosis; infarctus du myocarde; myocardial infarction; pioglitazone; produits terminaux de glycation; rat