Resveratrol Combined with Pioglitazone Ameliorates Cardiovascular Complications in db/db Diabetic Mice

Abstract

Type 2 Diabetes Mellitus patients are predisposed to serious cardiovascular morbidity and mortality. Diabetes causes different structural and functional alterations in the myocardial tissue, which are induced by hyperglycemia, insulin resistance, and hyperlipidemia. The resulting cardiomyopathy is characterized by myocardial fibrosis, dysfunctional remodeling and eventually, clinical heart failure. This study addressed the effects of resveratrol and pioglitazone to ameliorate diabetic cardiovascular complications using a db/db diabetic mice model. Male db/db diabetic mice were randomly assigned to orally receive resveratrol (50 mg/kg, n=5), resveratrol/pioglitazone (50 mg/kg and 20 mg/day, respectively, n=5) for the space of 6 weeks. Non-diabetic lean mice (n=5) were included as a control group. Histopathological analyses were performed in heart and aortic vessel tissue samples using hematoxylin and eosin, as well as Masson Trichromic staining. VCAM-1 immunohistochemistry was also assessed. Blood glucose, hemoglobin A1c, insulin, glycosuria, triglycerides, cholesterol, and LDL cholesterol were all examined. Present data suggest that the combination of pioglitazone plus resveratrol significantly lower circulating levels of insulin, hemoglobin A1c, glucose, triglycerides, cholesterol, and LDL levels. Our results also show that tissue damage to the heart and aortic vessels caused by diabetes can also be improved by the administration of said combination. The present study demonstrates that resveratrol/pioglitazone combination therapy improves carbohydrate and lipid metabolism, as well as improving diabetic cardiomyopathy in diabetic mice by producing a synergistic pharmacological effect. The combination of resveratrol plus pioglitazone has therapeutic potential against diabetic cardiomyopathy.