Aggravating effect of cigarette smoke exposure on experimental colitis is associated with leukotriene B(4) and reactive oxygen metabolites.
OBJECTIVE
Cigarette smoking is closely related to the development and recurrence of inflammatory bowel disease (IBD). The present study aimed to investigate the underlying mechanisms of the adverse action of cigarette smoke (CS) exposure on trinitrobenzene sulfonic acid (TNBS)-induced IBD.


METHODS
Rats were preexposed to CS once daily for 4 days before receiving a TNBS enema, and they were killed 24 h afterwards. The colonic myeloperoxidase (MPO) and xanthine oxidase (XO) activities, leukotriene B(4) (LTB(4)) and glutathione (GSH) levels, as well as the production of reactive oxygen metabolites (ROMs) were measured.


RESULTS
CS preexposure significantly augmented the adverse effects of the TNBS enema on colonic damage and increase in MPO activity, while it did not significantly alter the XO activity. Meanwhile, the elevation of ROM production and LTB(4) concentration in colonic tissues after the TNBS enema was also markedly enhanced by CS exposure. In contrast, the depressive action of the TNBS enema on cellular antioxidant GSH levels was reduced further by CS exposure. Pretreatment with a specific LTB(4) antagonist, ONO-4057, protected against colonic damage, particularly in the CS group.


CONCLUSIONS
CS exposure aggravated experimental IBD. This adverse action could be due to the depletion of GSH together with overproduction of LTB(4), followed by the accumulation of neutrophils and ROMs in the colonic tissue.
Guo
X
X
Department of Pharmacology, Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.
Ko
J K
JK
Mei
Q B
QB
Cho
C H
CH
D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D003093:Colitis, Ulcerative / Q000209:etiology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D005978:Glutathione / Q000032:analysis / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000473:pathology; D007975:Leukotriene B4 / Q000032:analysis / Q000378:metabolism*; D008163:Luminescent Measurements; D008297:Male; D009195:Peroxidase / Q000032:analysis / Q000378:metabolism*; D011336:Probability; D051381:Rats; D017207:Rats, Sprague-Dawley; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D014969:Xanthine Oxidase / Q000032:analysis / Q000378:metabolism*
D015415:Biomarkers; D014028:Tobacco Smoke Pollution; D007975:Leukotriene B4; D009195:Peroxidase; D014969:Xanthine Oxidase; D005978:Glutathione