title: Evaluation of the effects of a high dose of erythropoietin-beta on early endotoxemia using a rat model.
abstract: BACKGROUND
  Endotoxins can cause serious organ damage and death by triggering the secretion of pro-inflammatory cytokines such as TNF-alpha, IL-6 and IL-1beta in bacterial infections.
  
  
  OBJECTIVE
  The goal of this study was to evaluate the effects of a high dose (3000 U/kg) of erythropoietin-beta (EPO) on inflammatory cytokine levels, renal function and histological changes during the early period of Lipopolysaccharide (LPS)-induced endotoxemia using a rat model.
  
  
  METHODS
  Male Sprague Dawley (350-400 g) rats were randomized into 3 groups: Control group (n = 7); LPS group (received 20 mcg/kg LPS through intraperitoneal (i.p.) injection (n = 7); LPS+EPO group (received 3000 U/kg, ip 30 minutes before LPS administration (n = 7). Four hours after the administration of LPS, kidney tissue and serum samples were collected. Kidney function parameters, TNF-alpha, IL-6, IL-1beta, C reactive protein (CRP) and complete blood counts (CBC) were measured. The severity of renal tubular injury and caspase-9 immunoreactive cells was expressed as a percentage.
  
  
  RESULTS
  Serum levels of urea, creatinine, TNF-alpha, IL-6 and IL-1beta were significantly increased in the LPS group (p < 0.0001 - p = 0.04) and were lower in LPS+EPO group (p < 0.0001, p = 0.01, p = 0.02, p = 01 and p < 0.0001, respectively). Pretreatment with EPO significantly increased platelet counts (p = 0.00) and decreased white blood cell counts (p = 0.02). The renal tubular injury percentage was significantly higher in the LPS group than in the control and LPS+EPO groups (p = 0.002, p = 0.003, and p = 0.005, respectively) and caspase-9 expression was lower in the LPS+EPO and control groups than in the LPS group.
  
  
  CONCLUSIONS
  EPO might have renoprotective effects against the inflammatory process and cell apoptosis during endotoxemia.
authors.affiliation: Department of Nephrology, Yeditepe University Hospital, Istanbul, Turkey. zeheren@hotmail.com
authors.forename: Zehra
authors.initials: Z
authors.lastname: Eren
authors.forename: Jale
authors.initials: J
authors.lastname: Coban
authors.forename: Işin D
authors.initials: ID
authors.lastname: Ekinci
authors.forename: Cigdem
authors.initials: C
authors.lastname: Kaspar
authors.forename: Gülçlin
authors.initials: G
authors.lastname: Kantarci
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D019610:Cytoprotection; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D004921:Erythropoietin / Q000008:administration & dosage*; D018836:Inflammation Mediators / Q000097:blood; D007274:Injections, Intraperitoneal; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007958:Leukocyte Count; D008070:Lipopolysaccharides; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D010976:Platelet Count; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage; D012076:Renal Agents / Q000008:administration & dosage*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014508:Urea / Q000097:blood
chemical_list: D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D012076:Renal Agents; D014409:Tumor Necrosis Factor-alpha; C103998:epoetin beta; D004921:Erythropoietin; D014508:Urea; D002097:C-Reactive Protein; D003404:Creatinine; C506435:Casp9 protein, rat; D053453:Caspase 9