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

The current study aimed to investigate the possible beneficial effects of saxagliptin and escitalopram each alone or in combination on metabolic changes and cardiac complications in type 2 diabetic rats. Diabetes was induced by feeding the rats HFFD for 8 weeks followed by a subdiabetogenic dose of STZ (35 mg/kg, i.p.). Treatment with saxagliptin (10 mg/kg; p.o.) and escitalopram (10 mg/kg; p.o.) alone or in combination was continued for 4 weeks. At the end of the experiment, blood samples were collected for determination of serum parameters (glucose, insulin, fructosamine, HOMA-IR, TGs and TC). Animals were then euthanized and heart samples were collected for biochemical determinations (RAGE, NADPH oxidase, TAC, NF-mB, TNF-Ü, TGF-Ý1, caspase-8, p53, Ü-MHC, Ý-MHC and connexin-43) as well as histopathological examination. The HFFD/STZ model resulted in disturbances in both glycemic and lipid profiles along with an increase in BW. The model also induced myocardial damage that was evident by the increased oxidative stress, inflammation, fibrosis, apoptosis and hypertrophy as well as reduced conduction and contractility. Both saxagliptin and escitalopram alleviated the HFFD/STZ-induced metabolic and cardiac derangements. Combining both drugs promoted additional decreases in serum insulin, fructosamine and TC levels. Moreover, the combined regimen provided further improvement in controlling the diabetic-induced oxidative stress, inflammation, fibrosis, hypertrophy and contractility dysfunction which could be related to the reduction in RAGE content. Escitalopram thus could be considered a favorable antidepressant option in diabetic patients

Issued also as CD