Pantoprazole abrogated cisplatin-induced nephrotoxicity in mice via suppression of inflammation, apoptosis, and oxidative stress.

Abstract

The current study was designed to evaluate the potential abatement effect of pantoprazole against cisplatin-induced nephrotoxicity and establishing the possible protective mechanisms. Thirty-two male mice were allocated for treatment with saline, single dose of cisplatin (10mg/kg/i.p), pantoprazole (30mg/kg/once daily) for 5days or combination of pantoprazole and cisplatin for 5days. Urine, blood, and both kidneys were collected for further evaluations. Pantoprazole significantly countermand cisplatin-induced disfigurement of renal histology, kidney weight to body weight ratio, serum levels of creatinine and urea, and microalbuminuria. Furthermore, pantoprazole mostly normalized cisplatin-induced distortion of renal levels of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-6, interleukin-10) and renal content of apoptosis regulating protein expressions (Bax, Bcl2, and active caspase 3). In addition, pantoprazole significantly subsided cisplatin-induced distortion of renal lipid peroxidation marker (MDA), renal superoxide dismutase, and catalase activities and renal reduced glutathione content. This study provides an evidence for the protective utility of short-term pantoprazole against cisplatin-induced nephrotoxicity in mice. The protective mechanism of pantoprazole could be through diminution of cisplatin-induced inflammation, oxidative stress, and their subsequent apoptotic renal cell death via abatement of apoptosis regulating protein expressions (Bax, Bcl2, and active caspase3).