Combination Antioxidant Effect of Erythropoietin and Melatonin on Renal Ischemia-Reperfusion Injury in Rats

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 effect of co-administration of melatonin (MEL) and erythropoietin (EPO), potent antioxidant and anti-inflammatory agents, on IR-induced renal injury in rats. Wistar albino rats were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 24 hr reperfusion. MEL (10 mg/kg, IP) and EPO (5000 U/kg, IP) were administered prior to ischemia. After 24 hr reperfusion, following decapitation, renal samples were taken for the determination of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) levels and histological evaluation. The level of urea was measured in serum samples. Ischemia reperfusion significantly increased urea, and MDA levels, and decreased CAT and SOD activities. Histopathological findings of the IR group confirmed that there was renal impairment in the tubular epithelium. Treatment with EPO and MEL markedly decreased urea level and increased SOD and GPx activities. Treatment with EPO and MEL had a beneficial effect on renal IR injury. These results may show that the co-administration of MEL and EPO cannot exert more beneficial effects than either agent alone.