title: Melatonin synergistically enhances protective effect of atorvastatin against gentamicin-induced nephrotoxicity in rat kidney.
abstract: The risk of serious side-effects such 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 5 groups, each containing 6 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. Kidney 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, kidney 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, kidney weight, renal ROS and MDA levels. However ATO could not reduce these parameters, but similarly to MT, it was able to enhance the renal GSH level, CAT and SOD activity. In addition, a combination therapy of MT plus ATO enhanced the beneficial effects of ATO, while not changing the effects of MT effects or even improving them. The present study indicates that a combination therapy of MT plus ATO can attenuate renal injury in rats treated with GEN, possibly by reducing oxidative stress, and it seems that MT can enhance the beneficial effects of ATO.
authors.affiliation: a Razi Drug Research Center, Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Mehrzadi
authors.affiliation: b ENT- Head & Neck Research Center, Hazrate Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Seyed Kamran
authors.initials: SK
authors.lastname: Kamrava
authors.affiliation: c Department of Pediatric Nephrology, AJA University of Medical Science, Tehran, Iran.
authors.forename: Banafshe
authors.initials: B
authors.lastname: Dormanesh
authors.affiliation: a Razi Drug Research Center, Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Manijeh
authors.initials: M
authors.lastname: Motevalian
authors.affiliation: a Razi Drug Research Center, Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Azam
authors.initials: A
authors.lastname: Hosseinzadeh
authors.affiliation: d Department of Pediatric Nephrology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Seyed Mohammad Taghi
authors.initials: SM
authors.lastname: Hosseini Tabatabaei
authors.affiliation: e Cellular and Molecular Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.
authors.forename: Habib
authors.initials: H
authors.lastname: Ghaznavi
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D000069059:Atorvastatin / Q000494:pharmacology*; D003404:Creatinine / Q000097:blood; D004357:Drug Synergism; D005839:Gentamicins / Q000009:adverse effects*; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000000981:diagnostic imaging* / Q000378:metabolism; D007677:Kidney Function Tests / Q000379:methods; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D014508:Urea / Q000097:blood
chemical_list: D005839:Gentamicins; D020011:Protective Agents; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D014508:Urea; D000069059:Atorvastatin; D003404:Creatinine; D005978:Glutathione; D008550:Melatonin
keywords: atorvastatin; atorvastatine; gentamicin; gentamicine; melatonin; mélatonine; nephrotoxicity; néphrotoxicité; oxidative stress; rats; stress oxydatif