Protective role of cyclooxygenase inhibitors in the adverse action of passive cigarette smoking on the initiation of experimental colitis in rats

Clinical and experimental findings had indicated that cigarette smoke expos ure, and cyclooxygenase-2, are strongly associated with inflammatory bowel disease. The present study aimed to evaluate the role of cyclooxygenase-2 i n the pathogenesis of experimental inflammatory bowel disease as well as in the adverse action of cigarette-smoke exposure. Rats were pretreated with different cyclooxygenase-3 inhibitors (indomethacin, nimesulide. or SC-236 (4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonami de)) along with cigarette-smoke exposure before 2,4,6-trinitrobenzenesulfon ic acid-enema. Results indicated that pretreatment with cyclooxygenase-2 in hibitors not only protected against 2,4,6-trinitrobenzenesulfonic acid-indu ced inflammatory bowel disease, but also attenuated the potentiating effect of cigarette-smoke exposure on colonic damage. Furthermore, the colonic cy clooxygenase protein and mRNA expression was markedly induced by 2,4,6-trin itrobenzenssulfonic acid-enema, and it was potentiated further by cigarette -smoke exposure, while the cyclooxygenase-1 expression was not changed. The present study suggests that the highly induced cyclooxygenase-2 expression not only plays a pathogenic role in 2,4,6-trinitrobenzenrsulfonic acid-ind uced inflammatory bowel disease, but also contributes to the adverse action of cigarette-smoke exposure on this disorder. (C) 2001 Elsevier Science B. V. All rights reserved.