Role of granulocyte-macrophage colony-stimulating factor on apoptosis induced by ischemia-reperfusion in the intestinal epithelium

Eur Surg Res. 2003 Jul-Aug;35(4):357-62. doi: 10.1159/000070607.


Background: To evaluate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on ischemia-reperfusion-induced apoptosis in the intestinal epithelium.

Methods: In this study, 50 male Wistar albino rats were used. After midline laparotomy superior mesenteric artery (SMA) was identified only in the sham group, while 60 min of ischemia and 2 h of reperfusion were performed in the control group. In the treatment groups, after 15, 30 and 60 min of ischemia, respectively, 1 microg/kg GM-CSF was administered subcutaneously, followed by 2 h of reperfusion. Malondialdehyde (MDA), campothecin (CAM), an indicator of DNA fragmentation, and histopathology were evaluated in the intestinal mucosa.

Results: Tissue MDA levels were found significantly high in all groups at various times of ischemia and 2 h of reperfusion compared with the sham group (p < 0.001). Administration of GM-CSF following 60 min of ischemia caused a significant increase in the MDA levels compared with the control group (6430 +/- 725 vs. 4174 +/- 565 nmol/g protein for jejunum. 7576 +/- 618 vs. 4938 +/- 809 nmol/g protein for ileum, p < 0.05). Intestinal ischemia and reperfusion resulted in a significant increase in tissue CAM levels (p < 0.05). The highest CAM value was found in the group in which 60 min of ischemia and 2 h of reperfusion were performed (50 +/- 3.2 ng/ml for jejunum, 52.8 +/- 2.7 ng/mg for ileum). Compared with the control group, GM-CSF administration following 1 h of ischemia aggravated the tissue injury.

Conclusions: Apoptosis was induced in the small intestine by ischemia-reperfusion. GM-CSF increased the apoptosis of intestinal epithelial cells and exacerbated mucosal injury due to ischemia-reperfusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Camptothecin / metabolism
  • DNA Fragmentation / drug effects*
  • Endodeoxyribonucleases / metabolism
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
  • Ileum / metabolism
  • Ileum / pathology
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology*
  • Jejunum / metabolism
  • Jejunum / pathology
  • Male
  • Malondialdehyde / metabolism
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology*


  • Malondialdehyde
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Endodeoxyribonucleases
  • endonuclease NUC18
  • Camptothecin