Adverse action of cigarette smoke exposure on experimental colitis is associated with reactive oxygen metabolites and leukotriene B4

Background & Aim: Epidemiological studies clearly exemplified that cigarette smoking, including passive cigarette smoking, is an independent risk factor for the development and recurrence of inflammatory bowel disease (IBD), particularly Crohn's disease (CD) in humans. The present study aimed to investigate whether reactive oxygen metabolites (ROMs) and leukotriene B₄ (LTB₄) were involved in the adverse action of passive cigarette smoking on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model. Methods: Male Sprague-Dawley rats were pre-exposed to freshly prepared cigarette smoke (CS, 0%, 4%, v/v, smoke/air) once daily for 4 days, and TNBS/ethanol was administered intracolonically I hr after the last CS exposure. The rats were killed 2, 6 or 24 hr afterwards. The colonic tissue was extracted for determination of LTB4 and glutathione (GSH) levels in the tissue. The colonic ROMs were detected by a chemiluminescence assay in freshly excised colonic tissues. Results: It was found that CS exposure could significantly increase the colonic lesion area, tissue edema index as well as myeloperoxidase activity, when compared with the TNBS-enema control group. In the meantime, the amount of luminol dependent chemiluminescence from the colonic tissue were markedly
elevated by CS exposure, of which the significant increase had begun as early as 2 hr after TNBS-enema, and peaked at 24 hr. In addition, the GSH (an antioxidant) level in the tissue was significantly decreased following TNBS-enema, and was reduced further by CS exposure. Moreover, pretreatment with dimethyl sulfoxide (10%, 4 mllk.g, IP), a hydroxyl radical scavenger, had elicited protective effect on colonic damage and it was more pronounced in the smoke group. Similarly, LTB₄ concentration in the tissue was markedly augmented by CS exposure, which was elevated after TNBS-enema. Pretreatment with a LTB₄ receptor antagonist, ONO-4057 (100 mg/kg, p.o.), had protective effects as represented by reduction in colonic lesion and inflammation, especially in the smoke group. Conclusion: The above results suggest that the adverse action of CS exposure might be associated with the reduction of tissue antioxidant level as well as the potentiation of colonic ROMs and LTB₄ production.