Pharmacological preconditioning with erythropoietin reduces ischemia-reperfusion injury in the small intestine of rats.
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.
Sayan
Hale
H
Department of Physiology, Medical School, Zonguldak Karaelmas University, 67600 Kozlu Zonguldak, Turkey. halesayan@yahoo.com
Ozacmak
Veysel Haktan
VH
Sen
Feyza
F
Cabuk
Mehmet
M
Atik
Duygu Yoruk
DY
Igdem
Aysenur Akyildiz
AA
Ozacmak
Ihsan Diler
ID
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*
D011994:Recombinant Proteins; D004921:Erythropoietin; D008315:Malondialdehyde; D005978:Glutathione