Cross Talk between Oxidative Stress, PPAR- γ and RAS System in Diabetic Rat Heart Exposed to Ischemia / Reperfusion Injury

Abstract

Introduction: The present study aimed at clarifying the cross talk between peroxisome  proliferator-activated receptor-gamma (PPAR- γ), cardiac reactive Oxygen species (ROS) and Renin-Angiotensin System (RAS). Methods: A total of 90 male albino rats were used. The rats were divided into: Group 1: Control group, Group 2: Type 2 diabetic rats, Group 3: PPARγ agonist protected type 2 diabetic rats. Group 4: Antioxidant protected type2 diabetic rats, Group 5: Metformin treated type 2 diabetic rats. Blood samples were collected for measurement of FBS and fasting insulin. Half the number of each group was sacrificed and the heart excised and perfused, from the rest of the group small piece from the heart was taken for estimation of malondialdehyde (MDA), Angiotensin 2 Receptor (AT2R) and Angiotensin Converting Enzyme 2 (ACE2) gene expression. Results: Treatment with pioglitazone and Vitamin E significantly lowered blood glucose, insulin levels and Homeostasis Model Assessment Insulin Resistance (HOMA IR). However, values did not return to control values. Pioglitazone and Vitamin E improved myocardial performance and percentage recovery following ischemia reperfusion. The cardioprotective effect was more pronounced in the pioglitazone group. This positively correlated with decreased MDA levels and increased AT2R and ACE2 expression in cardiac tissue.  Conclusion: Pioglitazone and Vitamin E in type 2 DM significantly offered cardio-protection through improving the diabetic condition and / or decreasing MDA levels.