title: Erythropoietin attenuates experimental haemorrhagic shock-induced renal damage through an iNOS- dependent mechanism in male Wistar rats.
abstract: OBJECTIVE
  Erythropoietin (EPO) is shown to exert protective effects on different tissues in haemorrhagic shock (HS) states. Nitric oxide (NO), as a multifunctional signaling molecule, is implicated in diverse physiologic and pathologic processes. In order to understand the exact mechanism of EPO protection, in this study we evaluated the role of different NOS enzymes in the EPO signaling pathway in male rats.
  
  
  METHODS
  Rats were randomized to five groups: 1) Sham, 2) HS 3) EPO 4) L-NAME, a non-specific NOS inhibitor 5) 1400W, a specific iNOS inhibitor. HS was induced by withdrawal of 50% of total blood volume. After 2h, resuscitation was performed with the shed blood and Ringer's lactate. In group 3, rats were treated with EPO (300IU/kg, i.v.) over 10min before HS induction. In the L-NAME and 1400W groups, L-NAME (10mg/kg, i.p.) and 1400W (2mg/kg, i.p.) were administered 30min before EPO injection. Blood and kidney tissue samples were obtained 3h after resuscitation.
  
  
  RESULTS
  EPO increased the survival rate and significantly improved kidney function and histology compared to the HS group. There were less renal oxidative stress, apoptosis and systemic inflammatory responses in the EPO group. EPO increased eNOS and more abundantly iNOS mRNA expressions. L-NAME and 1400W significantly abolished all beneficial effects of EPO.
  
  
  CONCLUSIONS
  In this in vivo animal model, we showed that EPO administration prior to HS attenuates renal injury and dysfunction in rats. The protective effects of EPO may be mediated by nitric oxide and the expression of different NOS enzymes, especially iNOS isoform.
authors.affiliation: Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Ranjbaran
authors.affiliation: Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: kadkhodm@tums.ac.ir.
authors.forename: M
authors.initials: M
authors.lastname: Kadkhodaee
authors.affiliation: Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: B
authors.initials: B
authors.lastname: Seifi
authors.affiliation: Department of Clinical Biochemistry, School of Medicine, Tarbiat Modares University, Tehran, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Adelipour
authors.affiliation: Protein Chemistry Lab, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: B
authors.initials: B
authors.lastname: Azarian
mesh_terms: D058186:Acute Kidney Injury / Q000473:pathology*; D000818:Animals; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D012771:Shock, Hemorrhagic / Q000473:pathology*
chemical_list: D004921:Erythropoietin; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II
keywords: Erythropoietin; Haemorrhagic shock; Kidney; NOS inhibitor; Resuscitation