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.