Increased expression of cyclooxygenase-2 (COX-2) in radiation-induced small bowel injury in rats.
BACKGROUND
Radiation therapy is a widely used adjuvant therapy for various abdominal and pelvic cancers. On the other hand, it is not a benign treatment modality, as most radiation patients suffer from some kind of radiation enteritis. Currently available treatments are only palliative and no ideal compound has as yet been discovered. The aim of this study was to evaluate cyclooxygenase-2 (COX-2) expression, and to investigate the possible protective effect of the selective COX-2 inhibitor, Rofecoxib, in acute and late stages of radiation-induced intestinal injury in rats.


METHODS
Forty-eight male Sprague-Dawley rats were randomly divided into eight groups. After abdominal irradiation of all of the animals except the six in the control group, the expression of the enzyme cyclooxygenase-2 (COX-2) was evaluated in different cell types present in the intestinal wall 2 h post exposure (study day 0) and again on study days 4, 14, and 60. The effects of Rofecoxib on histological damage, intestinal myeloperoxidase (MPO) activity, and malondialdehyde (MDA) levels were also measured.


RESULTS
Expression of COX-2 in vascular endothelial cells was found to be significantly increased on post exposure days 4 and 14 (2.4 and 2.9 stained vessels/high power field [hpf] respectively compared to 1.3 vessels/hpf for controls) (P = 0.002). Expression of COX-2 in fibroblasts increased immediately after irradiation (29 cells/hpf 2 h after irradiation compared to 12 cells/hpf for non-irradiated control animals) and remained high during the entire study period (P < 0.001), whereas there was a peak COX-2 expression (54.9 cells/hpf) on day 14 that was similar to what was observed in endothelial cells. Irradiation of rats significantly increased intestinal epithelial damage, MPO activity, and MDA levels in comparison to the control group in a time-dependent fashion. Treatment with rofecoxib significantly decreased these elevations except on day 4 of the study.


CONCLUSIONS
The current study suggests that the COX-2 pathway is involved in radiation induced intestinal injury and that targeting COX-2 may be useful in limiting radiation enteritis.
Keskek
Mehmet
M
Department of 5(th) Surgery, Ankara Numune Training and Research Hospital, Ankara, Turkey. keskekm@yahoo.com
Gocmen
Erdal
E
Kilic
Mehmet
M
Gencturk
Serra
S
Can
Bilge
B
Cengiz
Mustafa
M
Okten
R Murat
RM
Koc
Mahmut
M
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D002908:Chronic Disease; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D004751:Enteritis / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D007421:Intestine, Small / Q000201:enzymology / Q000473:pathology / Q000528:radiation effects; D007783:Lactones / Q000494:pharmacology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013450:Sulfones / Q000494:pharmacology
D052246:Cyclooxygenase 2 Inhibitors; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; D008315:Malondialdehyde; D009195:Peroxidase; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat