Study of the possible cardioprotective effects of vitamin D and sitagliptin in Streptozotocin-induced diabetes in irradiated rats / Sara Aly Sanad Aly Ahmed ; Supervised Hala Ahmed Fahmy , Seham Hassan Mohammed , Suzan Mohammed Mansour

Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

Diabetic cardiomyopathy (DCM) is of high prevalence in diabetic patients. Exposure to Þ-radiation may be associated with many cardiovascular effects.This study aimed to investigate the ameliorative effects of sitagliptin, as well as vitamin D and their combination in DCM in Þ-irradiated animals. Diabetes mellitus was induced by single dose injection (50 mg/kg; i.p.) of streptozotocin (STZ). One week thereafter, rats exhibiting blood glucose (BG) level over 300 mg/dl were selected as a good DCM model and were treated with sitagliptin (100 mg/kg/day; p.o.) and/or vitamin D (2.5 æg/day; p.o.) for 2 weeks followed by exposure to a single dose of whole body Þ-radiation (3 Gy). Serum levels of BG, insulin, total cholesterol (TC), triglycerides (TG), reduced glutathione (GSH) and malondialdyhyde (MDA), as well as creatine kinase-MB (CK-MB) activity were determined Moreover, determination of apoptosis inducing factor (AIF) gene expression, in addition to, protein expression of Bcl-2-associated X protein (Bax), B cell lymphoma-2 (Bcl-2) and caspase-3, besides, the level of heat shock protein 70 (HSP-70) were also assessed in left ventricular tissue homogenate. Histopathological study of left ventricular tissue was carried out too. The present findings revealed that treatment with sitagliptin and/or vitamin D in presence or absence of Þ-irradiation ameliorated DCM-induced increase in serum levels of BG, TG, CK-MB and MDA coupled by increased insulin and GSH levels.Their cardioprotective potentials were further confirmed through attenuating the apoptotic process by mitigating Bax, caspase-3 and AIF expression while augmenting the anti-apoptotic factors, Bcl-2 and HSP-70. Such findings were coupled by marked amelioration of STZ-induced histopathological changes. In conclusion, treatment with sitagliptin and/or vitamin D with/without Þ-irradiation may prove beneficial in DCM. This could be attributed to simultaneous factors acting together including the antioxidant, anti-apoptotic and the ability to restore the body{u2019}s defense capacities

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