Recombinant human erythropoietin reduces rhabdomyolysis-induced acute renal failure in rats

Abstract

BackgroundRhabdomyolysis is one of the causes of acute renal failure. Erythropoietin (EPO) has been found to interact with its receptor (EPO-R) expressed in a large variety of non-haematopoietic tissues to induce a range of pleiotropic cytoprotective actions. In this study, we used recombinant human erythropoietin (rhEPO) to study the effects on the glycerol-induced rhabdomyolysis with acute renal failure in rats. MethodsTwenty-four rats were divided into three groups as glycerol group, glycerol+EPO group and normal saline+EPO group. Rhabdomyolysis was induced by intramuscular injection of 10mlkg−1 50% glycerol in rats. Ten minutes later, the rats received an intravenous injection of rhEPO (300Ukg−1). Biochemical substances, including haemoglobin, blood urea nitrogen (BUN), creatinine (Cre), glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) and creatine phosphokinase (CPK), were measured at 0, 1, 3, 6, 9, 12, 18, 24 and 48h. Rats were sacrificed 48h later after glycerol administration and the kidneys were removed immediately for pathology and immunohistochemistry (IHC). ResultsIntramuscular injection of glycerol significantly increased blood BUN, Cre, GOT, GPT and CPK levels and induced severe histopathologic damage in the kidneys. Nuclear factor-κB (NF-κB) and inducible nitric oxide synthase (iNOS) were increased and E-cadherin was decreased after glycerol administration, as detected by IHC in the kidneys. Post-treatment with rhEPO decreased blood BUN, Cre, GOT, GPT and CPK levels, decreased markers of kidney injury and suppressed the release of NF-κB and iNOS after rhabdomyolysis. ConclusionTreatment with rhEPO suppressed the activities of NF-κB and iNOS, decreased BUN, Cre, GOT, GPT and CPK levels, and decreased the markers of kidney injury after rhabdomyolysis. These actions ameliorated rhabdomyolysis-induced acute renal failure in rats.