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Renoprotective effect of erythropoietin in ischemia/reperfusion injury: Possible roles of the Akt/endothelial nitric oxide synthase‐dependent pathway
Author(s) -
Oba Shigeyoshi,
Suzuki Etsu,
Nishimatsu Hiroaki,
Kumano Shintaro,
Hosoda Chihiro,
Homma Yukio,
Hirata Yasunobu
Publication year - 2012
Publication title -
international journal of urology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.172
H-Index - 67
eISSN - 1442-2042
pISSN - 0919-8172
DOI - 10.1111/j.1442-2042.2011.02920.x
Subject(s) - erythropoietin , nitric oxide synthase , nitric oxide , medicine , nitric oxide synthase type iii , reperfusion injury , protein kinase b , ischemia , blood urea nitrogen , creatinine , renal ischemia , endocrinology , pharmacology , apoptosis , biology , enos , biochemistry
Objectives: It has been reported that erythropoietin protects the kidneys from ischemia/reperfusion injury. In the present study, we examined the role of Akt and endothelial nitric oxide synthase in the protective effect of erythropoietin on ischemia/reperfusion injury of the kidney. Methods: Erythropoietin was injected in the peritoneal space of ICR mice after ischemia/reperfusion injury and its effect was assessed by measuring blood urea nitrogen and creatinine, and by histological analysis. Phosphorylation of Akt and endothelial nitric oxide synthase was examined by western blot analysis. Endothelial nitric oxide synthase gene null mice were also used to examine the role of endothelial nitric oxide synthase in the renoprotective effect of erythropoietin. Results: Erythropoietin administration significantly inhibited the increase in blood urea nitrogen and creatinine after ischemia/reperfusion injury compared with control mice. Accordingly, erythropoietin administration significantly ameliorated the histological damages, including apoptotic cell death. Erythropoietin significantly stimulated phosphorylation of Akt and endothelial nitric oxide synthase in the kidneys. When endothelial nitric oxide synthase gene null mice were subjected to ischemia/reperfusion injury, erythropoietin did not significantly suppress the increase in blood urea nitrogen or creatinine. Conclusions: Erythropoietin seems to activate the Akt/endothelial nitric oxide synthase‐dependent pathway in the kidneys. This pathway might be implicated in the renoprotective effect of erythropoietin in the ischemia/reperfusion injury model.