The diverse actions of nicotine and different extracted fractions from tobacco smoke against hapten-induced colitis in rats.
The etiology of ulcerative colitis (UC) remains unknown, although the risk of developing UC is apparently higher in non-smokers and ex-smokers. We have demonstrated in a colitis animal model that exposure to tobacco smoke could attenuate UC pathogenesis. The present study aimed to investigate and compare between the modes of action of nicotine and different fractions of tobacco smoke extract in the development of experimental colitis. The hapten 2,4-dinitrobenzene sulfonic acid (DNBS) was used to induce colitis in Sprague-Dawley rats. Results indicated that both tobacco smoke exposure and subcutaneous nicotine differentially reduced colonic lesion size, myeloperoxidase (MPO) activity, luminol-amplified free radical generation, and leukotriene B4 formation in the inflamed colon of colitis animals. These phenomena were accompanied by the downregulation of colonic interleukin (IL)-1beta and monocyte chemoattractant protein (MCP)-1 protein expression. By treating the colitis animals with various tobacco extracts, we further discovered that ethanol extract from filtered tobacco smoke could attenuate DNBS-evoked colonic damage and the elevated MPO activity, while at the same time it downregulated colonic IL-1beta and MCP-1 protein expression. In contrast, the highest dose of the chloroform extract from the cigarette filter caused aggravating effects and overexpression of the pro-inflammatory cytokines and chemokines. These data suggest that effective attenuation of DNBS-induced colitis by tobacco smoke could be due to its nicotine content and possibly other flavonoid components found in the ethanol smoke extract.
Ko
Joshua K S
JK
School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China. jksko@hkbu.edu.hk
Cho
Chi-Hin
CH
D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics; D003092:Colitis / Q000517:prevention & control*; D003106:Colon / Q000378:metabolism; D004139:Dinitrofluorobenzene / Q000031:analogs & derivatives / Q000633:toxicity; D005609:Free Radicals / Q000378:metabolism; D007375:Interleukin-1 / Q000235:genetics; D008297:Male; D018375:Neutrophil Activation; D020556:Neutrophil Infiltration; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012906:Smoke
C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D005609:Free Radicals; D007375:Interleukin-1; D012906:Smoke; C045305:2,4-dinitrofluorobenzene sulfonic acid; D009538:Nicotine; D004139:Dinitrofluorobenzene