Erythropoietin protects the intestine against ischemia/ reperfusion injury in rats.

Previous studies have shown that erythropoietin (EPO) has protective effects against ischemia/reperfusion (I/R) injury in several tissues. The aim of this study was to determine whether EPO could prevent intestinal tissue injury induced by I/R. Wistar rats were subjected to intestinal ischemia (30 min) and reperfusion (60 min). A single dose of EPO (5000 U/kg) was administered intraperitoneally at two different time points: either at five minutes before the onset of ischemia or at the onset of reperfusion. At the end of the reperfusion period, jejunum was removed for examinations. Myeloperoxidase (MPO), malondialdehyde (MDA), and antioxidant defense system were assessed by biochemical analyses. Histological evaluation was performed according to the Chiu scoring method. Endothelial nitric oxide synthase (eNOS) was demonstrated by immunohistochemistry. Apoptotic cells were determined by TUNEL staining. Compared with the sham, I/R caused intestinal tissue injury (Chiu score, 3+/-0.36 vs 0.4+/-0.24, P<0.01) and was accompanied by increases in MDA levels (0.747+/-0.076 vs 0.492+/-0.033, P<0.05), MPO activity (10.51+/-1.87 vs 4.3+/-0.45, P<0.05), intensity of eNOS immunolabelling (3+/-0.4 vs 1.3+/-0.33, P<0.05), the number of TUNEL-positive cells (20.4+/-2.6 vs 4.6+/-1.2, P<0.001), and a decrease in catalase activity (16.83+/-2.6 vs 43.15+/-4.7, P<0.01). Compared with the vehicle-treated I/R, EPO improved tissue injury; decreased the intensity of eNOS immunolabelling (1.6+/-0.24 vs 3+/-0.4, P<0.05), the number of TUNEL-positive cells (9.2+/-2.7 vs 20.4+/-2.6, P<0.01), and the high histological scores (1+/-0.51 vs 3+/-0.36, P<0.01), and increased catalase activity (42.85+/-6 vs 16.83+/-2.6, P<0.01) when given before ischemia, while it was found to have decreased the levels of MDA (0.483+/-0.025 vs 0.747+/-0.076, P<0.05) and MPO activity (3.86+/-0.76 vs 10.51+/-1.87, P<0.05), intensity of eNOS immunolabelling (1.4+/-0.24 vs 3+/-0.4, P<0.01), the number of TUNEL-positive cells (9.1+/-3 vs 20.4+/-2.6, P<0.01), and the number of high histological scores (1.16+/-0.4 vs 3+/-0.36, P<0.05) when given at the onset of reperfusion. These results demonstrate that EPO protects against intestinal I/R injury in rats by reducing oxidative stress and apoptosis. We attributed this beneficial effect to the antioxidative properties of EPO.
AuthorsEnsari Guneli, Zahide Cavdar, Huray Islekel, Sulen Sarioglu, Serhat Erbayraktar, Muge Kiray, Selman Sokmen, Osman Yilmaz, Necati Gokmen
JournalMolecular medicine (Cambridge, Mass.) (Mol Med) 2007 Sep-Oct Vol. 13 Issue 9-10 Pg. 509-17 ISSN: 1076-1551 [Print] United States
PMID17873970 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Recombinant Proteins
  • Erythropoietin
  • Malondialdehyde
  • Catalase
  • Peroxidase
  • Glutathione Peroxidase
  • Nitric Oxide Synthase Type III
  • Superoxide Dismutase
  • Glutathione
  • Animals
  • Apoptosis (drug effects)
  • Catalase (metabolism)
  • Erythropoietin (administration & dosage, genetics, therapeutic use)
  • Glutathione (metabolism)
  • Glutathione Peroxidase (metabolism)
  • Humans
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Injections, Intraperitoneal
  • Intestines (blood supply, drug effects, pathology)
  • Male
  • Malondialdehyde (analysis)
  • Nitric Oxide Synthase Type III (metabolism)
  • Oxidative Stress (drug effects)
  • Peroxidase (analysis)
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Recombinant Proteins (therapeutic use)
  • Reperfusion Injury (drug therapy, etiology, prevention & control)
  • Superoxide Dismutase (metabolism)

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