[Mechanism of exacerbation of colonic damage in experimental colitis treated with celecoxib].
OBJECTIVE
To assess the mechanism of exacerbation of colonic damage in rat colitis model induced by trinitrobenzene sulfonic acid (TNBS) treated with celecoxib (a selective COX-2 inhibitor).


METHODS
The rats were randomized into four groups. Group 1 and Group 2 were study groups. Group 3 and Group 4 were control groups. Colitis was induced by intracolonic administration of TNBS (25 g/L) in a vehicle of 50% ethanol (0.25 mL) of study groups. The rats of study groups were treated orally, beginning 3 h before induction of colitis and continuing twice per day thereafter for up to 7 d, with celecoxib (1.25 mg/kg, Group 1) and distilled water (1 mL/0.3 kg, Group 2) respectively. In control experiments, the rats of Group 4 were treated orally with celecoxib (1.25 mg/kg) twice per day for up to 7 d. Group 3 rats were healthy control rats. All the rats that survived until the end of the experiment (d 7) were killed and the severity of colonic inflammation was assessed. The COX-2 protein expression in colon tissues was examined by immunohistochemistry.


RESULTS
The colonic damage of Group 1 was exacerbated as compared with Group 2. The inflammatory index of colon tissues of Group 1 (8.5+/-2.5) was significantly reduced, as compared with Group 2 (13.5+/-1.9, P<0.05). The levels of COX-2 protein expression was decreased significantly in Group 1 (3.7 x 10(-2)+/-9.5 x 10(-3)) as compared with Group 2 (11.4 x 10(-2)+/-3.8 x 10(-2), P<0.05). The positive rate of COX-2 expression in neural cells of the myenteric plexus in Group 1 (30%) was decreased as compared with Group 2 (90%, P<0.05). No difference was found in the inflammatory index, the levels of COX-2 protein expression and the positive rate of COX-2 expression in neural cells of the myenteric plexus of Group 3 and Group 4.


CONCLUSIONS
Selective COX-2 inhibitor-celecoxib could decrease the expression of COX-2 in intestinal tissue, attenuate the inflammatory index of colon tissues of experimental colitis induced by TNBS. But the application of celecoxib resulted in exacerbation of colonic damage. These adverse events are probably relevant to the suppression of COX-2 expression in the neural cells of the myenteric plexus, leading to decrease of intestinal contractivity and peristalsis, enteroparalysis, megacolon and death of the rat.
Zhang
Ling
L
Department of Gastroenterology, Peking University Third Hospital, Beijing 100083, China.
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Yu min
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Ye
Si mao
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Dong
Xiu yun
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D000818:Animals; D000068579:Celecoxib; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D003106:Colon / Q000378:metabolism / Q000473:pathology*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D008297:Male; D011720:Pyrazoles / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000627:therapeutic use*; D014302:Trinitrobenzenesulfonic Acid
D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D014302:Trinitrobenzenesulfonic Acid; D051546:Cyclooxygenase 2; D000068579:Celecoxib