Effect of Quercetin and Glibenclamide Combination on PPAR-γ and Oxidative Stress: A Study on Cardiac Tissue of Diabetic Animal Model

Abstract

INTRODUCTION: Type 2 diabetes mellitus (DM) contributes to cardiac failure through oxidative stress and reduced expression of peroxisome proliferator-activated receptor-γ (PPAR-γ). PPAR-γ plays a protective role by enhancing metabolism and mitigating oxidative stress. Quercetin has been shown to activate PPAR-γ and reduce lipid peroxidation. This study aims to evaluate the effects of combining quercetin with glibenclamide on cardiac PPAR-γ expression and lipid peroxidation in diabetic rats. MATERIALS AND METHODS: This experimental study involved 25 paraffin-embedded cardiac tissue samples from three-month-old Wistar rats, divided into five groups: healthy control, diabetic control (placebo), diabetic with glibenclamide (5 mg/kg/day), diabetic with quercetin (20 mg/kg/day), and diabetic with both glibenclamide and quercetin. Treatments were administered orally for 4 weeks. Cardiac PPAR-γ expression was assessed via immunohistochemistry, and malondialdehyde levels were measured using the thiobarbituric acid reactive substances (TBARS) assay. RESULTS: Both quercetin and glibenclamide monotherapies significantly increased cardiac PPAR-γ expression. However, the combination therapy further enhanced PPAR-γ expression compared to either treatment alone (p<0.05). Malondialdehyde levels significantly decreased in all treated diabetic groups compared to the diabetic control, with no significant difference between monotherapy and combination groups. CONCLUSION: The combination of quercetin and glibenclamide enhances cardiac  PPAR-γ expression more effectively than monotherapy, while reducing lipid peroxidation to a similar extent. This suggests potential synergistic benefits in managing oxidative stress-related cardiac complications in type 2 DM.