Thesis (M.Sc.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

Type -II- diabetes mellitus prevalence and incidence is rapidly increasing worldwide; it is predicted, according to the latest estimates of the world health organization (WHO), that diabetes will be the 7th leading cause of death in 2030. The present study was constructed in order to investigate the possible beneficial anti-diabetic effect of simultaneous administration of quercetin (bioflavonoid, 50 mg/kg,p.o.) with either sitagliptin (DPP-IV inhibitor, 70 mg/kg,p.o) or gliclazide (10 mg/kg, p.o.) in streptozotocin (STZ, 45 mg/kg, i.p.) - induced type -II- diabetic rats. In order to achieve the goals of the present study, serum glucose, C-peptide, total cholesterol, triglycerides, malondialdehyde (MDA), tumor necrosis factor alpha (TNF-Ü) and adiponectin levels were measured at the end of the study period (3 consecutive weeks). In addition, histopathological, morphometrical and immunohistochemical examination of pancreas was conducted. Daily oral administration of diabetic rats with gliclazide significantly reduced serum glucose, MDA, TNF-Ü and significantly increased serum C-peptide and adiponectin levels, in addition normalized serum total cholesterol and triglycerides levels. Daily oral administration of sitagliptin or quercetin significantly reduced serum glucose, MDA and significantly increased serum C-peptide and adiponectin levels, as well as normalized serum total cholesterol, triglycerides and TNF-Ü levels. Moreover, all single treatments induced significant improvement in islet and beta cell parameters (number and size) and in the immunostaining intensity. Combined administration of quercetin with gliclazide ameliorated the hyperglycemia, as well as significantly increased the serum C-peptide level; in addition it normalized MDA, TNF-Ü and adiponectin levels

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