The accelerated healing effects of passive cigarette smoking and nicotine on DNBS-induced colitis through the inhibition of neutrophil-derived free radicals

Human epidemiological findings had indicated that smokers have a reduced risk of developing ulcerative colitis (UC). However, the detail explanation for this phenomenon still remains unclear. The present investigation aimed to reveal the effect of passive cigarette smoking and the contribution of nicotine in UC development.We hypothesized that both cigarette smoke and nicotine could have beneficial effects on experimental
colitis. 2,4-Dinitrobenzene sulfonic acid (DNBS) was used to induce
human UC-like colitis in male Sprague-Dawley rats. Some animals were exposed to a fixed concentration (4% v/v) of filtered or non-filtered cigarette smoke one hour daily for 3 days in a ventilated smoking chamber following DNBS administration. Our results showed that exposure of the rats to either filtered or non-filtered cigarette smoke had enhanced the healing of DNBS-induced colitis, when compared with the DNBS-treated
control animals. This was indicated by the reduction in colonic lesion area, macroscopic damage score, histologic damage score, myeloperoxidase activity, and the apoptosis I cell proliferation ratio. On the other hand, post-DNBS subcutaneous injection of nicotine in two regimens (three daily
doses of 4mg/kglday or a single dose of 8mg/kg) had promoted colonic healing effect in the colitis animals in a similar fashion. All these therapeutic treatments had demonstrated a reduction in the amount of myeloperoxidase-derived free radicals in the colonic tissue by using a luminolamplified chemiluminescence method. Moreover, MK886, a 5-lipoxygenase inhibitor which could suppress the biosynthesis of leukotriene B₄, was also shown to have beneficial effect on the experimental colitis. In summary, both passive cigarette smoking and subcutaneous nicotine treatment
could accelerate the healing of experimental colitis in rats. The underlying mechanisms involve the attenuation of neutrophil activation, reduction in free radicals formation and subsequently prevention of apoptosis in the inflamed colon.