title: Combination Anti-Apoptotic Effect of Erythropoietin and Melatonin on Ischemia Reperfusion-Induced Renal Injury in Rats.
abstract: Renal ischemia-reperfusion (IR) contributes to the development of acute renal failure (ARF). Oxygen free radicals are considered to be principal components involved in the pathophysiological tissue alterations observed during renal IR. The purpose of this study was to investigate the combination effect of melatonin (MEL) and erythropoietin (EPO), which are a potent antioxidant and anti-apoptotic agents, in IR-induced renal injury in rats. Wistar Albino rats were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 24 h reperfusion. MEL (10 mg/kg, i.p) and EPO (5000 U/kg, i.p) were administered prior to ischemia. After 24 h reperfusion, following decapitation, blood samples were collected for the determination of superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) levels. Also, renal samples were taken for histological evaluation and apoptosis assay. Ischemia-reperfusion increased SOD, GPx, MDA levels, and TUNEL positive cells. Histopathological findings of the IR group confirmed that there was renal impairment in the tubular epithelium. Treatment with EPO and MEL decreased SOD, GPx, and MDA levels, histopathological changes, and TUNEL positive cells. These results indicated that the combination of MEL and EPO could not exert more nephroprotective and anti-apoptotic effects than MEL treatment in renal ischemia-reperfusion injury.
authors.affiliation: Department of Physiology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.
authors.forename: Shokofeh
authors.initials: S
authors.lastname: Banaei
authors.affiliation: Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Nasser
authors.initials: N
authors.lastname: Ahmadiasl
authors.affiliation: Department of Histology and Embryology, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Alihemmati
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000494:pharmacology*; D005979:Glutathione Peroxidase; D008297:Male; D008315:Malondialdehyde; D008550:Melatonin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000139:chemically induced*; D013482:Superoxide Dismutase
chemical_list: D000975:Antioxidants; C554270:EPO protein, human; D004921:Erythropoietin; D008315:Malondialdehyde; D000068817:Epoetin Alfa; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D008550:Melatonin
keywords: Apoptosis; Erythropoietin; Lipid peroxidation; Melatonin; Renal ischemia reperfusion