A novel therapeutic combination of vildagliptin and agomelatine alleviates the nephropathy in streptozocininduced diabetic rats: A structural & biochemical study

Diabetes mellitus is a worldwide epidemic causes numerous health problems including nephropathy and depression which are caused by oxygen radicals. We investigated the antioxidative effects of agomelatine or vildagliptin on streptozotocin-induced diabetic nephropathy in rats. 50 male albino rats were distributed into five groups, (n = 10/ group): the normal control, A single intraperitoneal injection of streptozotocin was given to the other four groups to induce diabetes at a dose of 60 mg/kg body weight. After diabetes induction, one of the groups was chosen as a positive control. Other rats were treated with either vildagliptin (10 mg/kg) and/or agomelatine (20 mg/kg/day) daily for 4 weeks. We used different biochemical parameters (blood glucose level, insulin levels, oxidative stress markers) as well as histological analysis on the kidney tissues of the experimental animals. Statistical evaluation was performed by Oneway ANOVA for comparison of those groups followed by Duncan's post hoc test for multiple group comparison. Diabetes induced nephropathy via oxidative pathway as this was confirmed by increased serum levels of urea, uric acid and creatinine with decrease in serum total antioxidant Capacity (TAC) in diabetic rats compared to control rats. Also, there were significant increase in renal levels of malondialdehyde (MDA) and nitric oxide (NO); significant decrease in the levels of renal glutathione (GSH) and superoxide dismutase (SOD) in diabetic group compared to the control group. Administration of either vildagliptin and/or agomelatine or both to diabetic rats alleviated the previous indices as confirmed by the biochemical and histological changes with better improvement in (vildagliptin+agomelatine) to that of vildagliptin treatment alone. Conclusion: Combination of agomelatine and vildagliptin could ameliorate diabetic nephropathy through inhibition of oxidative stress.