Intrarectal nitric oxide administration prevents cellular infiltration but not colonic injury during dextran sodium sulfate colitis.

BACKGROUND: During inflammation in the gastrointestinal tract, the production of nitric oxide (NO) is mediated by the mucosal conversion of L-arginine. Recently, it was shown that the gut microbiota can also produce NO. AIMS: The effect of gut luminal NO on inflammatory processes of an experimental colitis mice model was investigated by administrating NO directly to the colon, mimicking microbial NO production.
METHODS: Twenty-four mice received daily intrarectal treatment with a NO donor in 2 doses and 8 mice were treated with placebo. Starting 1 day later, 18 of these mice were fed ad libitum with 4% of dextran sodium sulfate (DSS) in their drinking water to induce colitis. At day 6, histopathology (both the inflammation and damage score), myeloperoxidase (MPO)-activity, colon length and colonic permeability were evaluated.
RESULTS: Co-administration of NO during DSS exposure inhibited the induction of an increasing colonic MPO-activity. This protective effect of NO was confirmed by the histological inflammation score showing a similar trend. The colonic permeability was restored when very low levels of NO were administered to the DSS-mice. On the other hand, the colon length of the NO-treated DSS-mice was negatively correlated with the NO dose and the histological damage score was not improved.
CONCLUSIONS: Our results indicate that intrarectal administration of NO has clear anti-inflammatory effects in experimental colitis, but does not prevent colonic damage. Therefore, NO-producing microorganisms in the gut lumen should be accounted as a modulating process during colitis.