Melatonin synergistically enhances protective effect of atorvastatin against gentamicin-induced nephrotoxicity in rat kidney

The risk of serious side-effects as nephrotoxicity is the principal limitation of gentamicin (GEN) therapeutic efficacy. Oxidative stress is considered to be an important mediator of GEN-induced nephrotoxicity. The present study was designed to evaluate the efficacy of the combination of melatonin (MT) plus atorvastatin (ATO) against GEN-induced nephrotoxicity in rats. We utilized 30 male Wistar albino rats allocated in five groups each containing six rats: control, GEN (100 mg/kg/day), ATO (10 mg/kg/day) + GEN, MT (20 mg/kg/day) + GEN and ATO (10 mg/kg/day) plus MT (20 mg/kg/day) + GEN. Kidneys weight, serum creatinine and urea concentration, renal ROS, MDA, GSH levels, SOD and CAT activity were determined. GEN-induced nephrotoxicity was evidenced by marked elevations in serum urea and creatinine, kidneys weight, renal ROS and MDA levels and reduction in renal GSH level, SOD and CAT activity. MT pretreatment significantly lowered the elevated serum creatinine concentration, kidneys weight, renal ROS and MDA levels but ATO couldn’t reduce these parameters but similar to MT it was able to enhance the renal GSH level, CAT and SOD activity. In addition, combination therapy of MT plus ATO enhanced the beneficial effects of ATO while didn’t change MT effects or even improve it. The present study indicates that combination therapy of MT plus ATO can attenuate renal injury in rats treated with GEN, possibly by reducing oxidative stress and it seems MT can enhance beneficial effects of ATO.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author