The Possible Protective Effect of Resveratrol Alone or in Combination with Metformin on Diabetic Cardiomyopathy in Adult Male Rats

Diabetes mellitus (DM) is commonly associated with metabolic alterations and various complications. Resveratrol (RSV) is a natural polyphenolic compound with multiple beneficial activities. The current study investigated the potential cardioprotective role of RSV, administered alone or with a standard anti-diabetic drug, metformin (MET), in type 2 diabetic rat model. Type 2 DM was induced in the current study by administration of a high fat diet (HFD) and a single dose of streptozotocin (STZ). Male rats were classified into 5 groups; normal control, diabetic, MET-treated diabetic, RSV-treated diabetic and MET&RSV-treated diabetic rats. Fasting plasma glucose (FPG), plasma insulin, homeostasis model assessment for insulin resistance (HOMA-IR), cardiac injury markers, oxidative/antioxidative stress markers and apoptotic genes expression were measured. Cardiac histopathological study was also performed. Diabetic rats exhibited significant increase in FPG, insulin, HOMA-IR, troponin I, creatine kinase-MB, malondialdehyde as well as glycogen synthase kinase-3β (GSK-3β) and BAX gene expressions, while a significant reduction in reduced glutathione and Bcl-2 gene expression was observed. These changes were coupled by marked histological alterations of the examined cardiac tissue in comparison to the control group. The altered parameters were improved by treatment with MET, RSV, or both. HFD/STZ resulted in characteristic metabolic features of type 2 DM with elevation of markers of cardiac injury, oxidative stress, and apoptosis. Concomitant treatment with MET and RSV revealed synergistic effect in most of studied parameters, demonstrating that RSV could improve the medicinal efficacy of MET.