title: Pharmacological preconditioning with erythropoietin reduces ischemia-reperfusion injury in the small intestine of rats.
abstract: OBJECTIVE
  Considering the implications that arose from several recent experimental studies using recombinant human erythropoietin in rodents, erythropoietin has been regarded as a pharmacological preconditioning agent. The purpose of the present study was to evaluate whether erythropoietin has a preconditioning effect against ischemia and reperfusion injury in the small intestine of the rat.
  
  
  METHODS
  Intestinal ischemia was induced in male Wistar rats by clamping the superior mesenteric artery for 30 min, followed by reperfusion for 180 min. Recombinant human erythropoietin (1000 or 3000 U/kg) or vehicle was administered intraperitoneally 24 h prior to ischemia. After collection of ileal tissue, evaluation of damage was based on measurements of the accumulation of polymorphonuclear neutrophils by technetium-99m-labeled leukocyte uptake, content of malondialdehyde, reduced glutathione, contractile responses to agonists, and an evaluation of histopathological features in intestinal tissue.
  
  
  RESULTS
  Treatment with erythropoietin 24 h before ischemia significantly reduced the tissue content of malondialdehyde and increased that of reduced glutathione. Pretreatment also significantly suppressed leukocyte infiltration into the postischemic tissue, as evidenced by the lower content of myeloperoxidase and technetium-99m-labeled leukocytes. Physiological and histopathological improvements were also significant with the rHuEpo treatment.
  
  
  CONCLUSIONS
  Results of the present study indicate that rHuEpo is an effective preconditioning agent in ischemic injury of the small intestine. Protection provided by recombinant human erythropoietin is closely related to the inhibition of oxidative stress and leukocyte infiltration, which might be among the possible protective mechanisms of erythropoietin in intestinal ischemia and reperfusion.
authors.affiliation: Department of Physiology, Medical School, Zonguldak Karaelmas University, 67600 Kozlu Zonguldak, Turkey. halesayan@yahoo.com
authors.forename: Hale
authors.initials: H
authors.lastname: Sayan
authors.forename: Veysel Haktan
authors.initials: VH
authors.lastname: Ozacmak
authors.forename: Feyza
authors.initials: F
authors.lastname: Sen
authors.forename: Mehmet
authors.initials: M
authors.lastname: Cabuk
authors.forename: Duygu Yoruk
authors.initials: DY
authors.lastname: Atik
authors.forename: Aysenur Akyildiz
authors.initials: AA
authors.lastname: Igdem
authors.forename: Ihsan Diler
authors.initials: ID
authors.lastname: Ozacmak
mesh_terms: D000818:Animals; D004921:Erythropoietin / Q000008:administration & dosage / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007082:Ileum / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007274:Injections, Intraperitoneal; D007962:Leukocytes / Q000166:cytology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
chemical_list: D011994:Recombinant Proteins; D004921:Erythropoietin; D008315:Malondialdehyde; D005978:Glutathione