Metformin as a protective substance against cisplatin-induced acute renal injury in rats

Abstract

Despite the efficacy of cisplatin as a chemotherapeutic agent against various cancers, its clinical utility is limited by serious adverse reactions including nephrotoxicity. Various studies revealed that metformin is more than a simple antidiabetic agent. Metformin was found to improve inflammatory, and fibrotic renal damage. The present study aims to investigate the protective effect of metformin against cisplatin-induced acute renal injury in rats. 40 adult male albino rats were divided into 4 groups with 10 rats in each group. Group I (control group). Group ІІ animals receive metformin at a dose of 200 mg/kg/day by oral gavage for 10 days. Group ІІI animals receive a single injection of cisplatin intraperitoneally at a dose of 8 mg/kg. Group ІV animals receive cisplatin Plus metformin. At the end of the experiment, the kidneys were removed, weighed, and sampled for histopathological, immunohistochemical, and biochemical studies. Metformin decreased elevated serum creatinine, blood urea nitrogen, renal malondialdehyde (MDA) and immunoexpression of the proapoptotic protein (Bax) induced by cisplatin. It increased reduced glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and immunoexpression of the antiapoptotic protein (Bcl2). It also ameliorated the morphological changes induced by cisplatin. Cisplatin has nephrotoxic effects as indicated by biochemical, histological, and immunohistochemical alterations. Metformin was found to have protective effects against cisplatin-induced nephrotoxicity through the improvement of kidney function, and histopathological changes in rat kidney.