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

Document Type : Original Article

Authors

1 Clinical pharmacology department faculty of medicine zagazig university

2 Pharmacology Department, Faculty of Medicine, Zagazig University

3 Pathology Department - Faculty of Medicine - Zagazig University -Zagazig - sharkeya - Egypt

Abstract

Background: Myocardial infarction is a critical complication frequently occurs with type2diabetes mellitus. Sitagliptin is antidiabetic drug inhibits DPP-4,which augments endogenous levels of GLP-1.Metformin is an FDA-approved antidiabetic drug, which commonly prescribed for management ofT2DM.Objectives: Is to investigate the possible beneficial effects of sitagliptin, metformin, and their combination on myocardial ischemic and vascular changes in T2Drats and possible mechanisms underlying this effects
Methods: Adult male albino rats were used in this study and randomly divided into control normal group, control diabetic group , sham diabetic group and diabetic with induction of MI group. Diabetic rats with MI were divided into the following treated subgroups: Oral Sitagliptin (300 mg/kg/day),Metformin(120mg/kg/day)and Combined metformin sitagliptin treated subgroups for6weeks. bl gl level, serum TG and LDL levels, markers of oxidative stress(vascular MDA and cardiac SOD levels),inflammation marker(plasmaIL6),and plasma CK-MB were measured. Hematoxylin and Eosin stained sections of cardiac tissue were examined. vascular reactivity of thoracic aortas were measured.
Results:DMT2with induction of MI evoked oxidative stress, inflammation, as well as histopathological derangements in cardiac tissue and decrease 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 T2Drats but combined administration of metformin sitagliptin was superior to each drug alone in cardiovascular protection effects. This protective effects of sitagliptin may be due to its anti-inflammatory and antioxidant potentials.

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