The protective effect of metformin and exenatide on doxorubicin-induced nephrotoxicity in rats

Abstract

Objective The aim was to study the protective effect of metformin and exenatide on doxorubicin (DOX)-induced nephrotoxicity in rats. Background DOX is an effective chemotherapeutic agent used for treatment of various solid as well as hematological neoplasms. Its use is limited owing to well-documented nephrotoxicity. Treatment with metformin and exenatide ameliorates nephrotoxicity in rats through antioxidant and antiapoptotic effects. Materials and methods In this experimental study, rats were divided as follows: group 1 was injected with saline intraperitoneal and orally, group 2 was injected with intraperitoneal DOX (15 mg/kg) and oral saline, group 3 was injected with intraperitoneal DOX and received metformin (250 mg/kg/day) orally, group 4 was injected with intraperitoneal DOX and received exenatide (10 μg/kg twice daily) Sc, and group 5 was injected with intraperitoneal DOX and metformin + exenatide. Basal body weight (Wt.), final body Wt., kidney Wt., kidney index, kidney malondialdehyde (MDA), reduced glutathione (GSH), serum tumor necrosis factor-α (TNF-α), serum albumin, serum urea and creatinine, urinary proteins, histopathological examination of hematoxylin and eosin, and caspase-3 immunostaining were evaluated. Results DOX group showed a significant decrease in body Wt, GSH levels, and serum albumin, with an increase in kidney Wt., kidney index, serum TNF-α, kidney MDA levels, urine proteins, serum urea and creatinine, and caspase-3 immunoexpression compared with the control group. In contrast, metformin-, exenatide-, and metformin + exenatide-treated groups showed significant increase in body Wt. and kidney GSH levels, with a decrease in kidney Wt., serum TNF-α, kidney MDA levels, and caspase-3 immunoexpression compared with DOX group. Conclusion Metformin and exenatide improved DOX nephrotoxicity in rats.