Involvement of neutrophils and free radicals in the potentiating effects of passive cigarette smoking on inflammatory bowel disease in rats.
OBJECTIVE
Cigarette smoking is associated with inflammatory bowel diseases (IBDs), particularly Crohn's disease, in humans. The aim of this study was to examine whether passive cigarette smoking aggravates experimental IBD in rats and to clarify the underlying mechanisms.


METHODS
Rats were exposed to cigarette smoke (CS) for 1 hour once daily for 4 days before induction of IBD by 2,4, 6-trinitrobenzene sulfonic acid (TNBS)-ethanol enema and were then killed at 2, 6, or 24 hours later.


RESULTS
Preexposure to CS significantly potentiated colonic damage induced by TNBS. TNBS-ethanol enema caused a pronounced increase in colonic myeloperoxidase activity, leukotriene B(4) level, and also inducible nitric oxide synthase activity, its protein, and messenger RNA expression. These parameters were all significantly increased further by exposure to CS. In contrast, increased colonic superoxide dismutase activity after TNBS-ethanol enema was attenuated by CS exposure. The potentiating effects of CS exposure on TNBS-induced IBD were significantly alleviated after pretreatment with cyclosporin A (an immunosuppressant), N (G)-nitro-L-arginine methylester (a nitric oxide synthase inhibitor), and dimethyl sulfoxide (a hydroxyl radical scavenger).


CONCLUSIONS
The results show that promotion of neutrophil infiltration and free radical production contributed significantly to the potentiating effect of passive cigarette smoking on experimental IBD.
Guo
X
X
Department of Pharmacology, Faculty of Medicine, University of Hong Kong, Hong Kong, P. R. China.
Wang
W P
WP
Ko
J K
JK
Cho
C H
CH
D000818:Animals; D003106:Colon / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D004733:Enema; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology; D005609:Free Radicals / Q000494:pharmacology; D015212:Inflammatory Bowel Diseases / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology*; D007975:Leukotriene B4 / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013482:Superoxide Dismutase / Q000378:metabolism; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D014302:Trinitrobenzenesulfonic Acid / Q000008:administration & dosage / Q000494:pharmacology
D005609:Free Radicals; D012333:RNA, Messenger; D014028:Tobacco Smoke Pollution; D007975:Leukotriene B4; D000431:Ethanol; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D013482:Superoxide Dismutase