Role of granulocyte-macrophage colony-stimulating factor on apoptosis induced by ischemia-reperfusion in the intestinal epithelium.
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.
Bedirli
A
A
Department of General Surgery, University of Erciyes, School of Medicine, Kayseri, Turkey. bedirlia@erciyes.edu.tr
Soyuer
I
I
Muhtaroglu
S
S
Guler
I
I
D000818:Animals; D002166:Camptothecin / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects*; D004706:Endodeoxyribonucleases / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D007082:Ileum / Q000378:metabolism / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology*; D007583:Jejunum / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*
D008315:Malondialdehyde; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004706:Endodeoxyribonucleases; C071211:endonuclease NUC18; D002166:Camptothecin