Beneficial effects of sitagliptin ,metformin and their combination on myocardial ischemic and vascular changes in type-two diabetic rats

Abstract

Background: Myocardial infarction is a critical complication frequently occurs with type 2 diabetes mellitus (T2DM). Sitagliptin is antidiabetic drug inhibits DPP-4,which augments endogenous level of glucagon like peptide 1(GLP-1).Metformin is an FDA-approved antidiabetic drug, which is commonly prescribed for management of T2DM. Objectives: Is to investigate the possible beneficial effects of sitagliptin, metformin, and their combination on myocardial ischemic and vascular changes in T2D rats and possible mechanisms underlying these effects. Methods: Adult male albino rats were used in this study and were randomly divided into control normal group, control diabetic group , sham diabetic group and diabetic with induction of MI group. Diabetic rats with myocardial infarction(MI) were divided into the following treated subgroups: Oral Sitagliptin (300 mg/kg/day), Metformin(120mg/kg/day) and Combined metformin sitagliptin treated subgroups for 6 weeks. blood glucose (bl gl) level, serum Triglycerides (TG) and Low-density lipoprotein (LDL) levels, markers of oxidative stress(vascular Malondialdehyde (MDA) and cardiac Superoxide dismutase(SOD)levels),inflammation marker(plasma Interleukin-6( IL6),and plasma Creatin kinase-MB (CK-MB) were measured. Hematoxylin and Eosin stained sections of cardiac tissue were examined. vascular reactivity of thoracic aortas were measured. Results:DMT2 with induction of MI evoked oxidative stress, inflammation, as well as histopathological derangements in cardiac tissue and decreased vascular reactivity. Treatment with sitagliptin , metformin and their combination improved the cardiac histopathological changes and vascular reactivity as well as attenuating the oxidative stress and inflammatory processes. Conclusion: Sitagliptin has beneficial protective effects against myocardial ischemic changes induced in T2D rats but combined administration of metformin sitagliptin was superior to each drug alone in cardiovascular protection effects. This protective effect of sitagliptin may be due to its anti-inflammatory and antioxidant potentials.