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

Abstract

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. 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. 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. 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. 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