Endogenous and Exogenous Hydrogen Sulfide Promotes Resolution of Colitis in Rats

BACKGROUND & AIMS: Hydrogen sulfide (H2S) is an endogenous gaseous mediator of mucosal defense with antiinflammatory effects that promote ulcer healing. The effects of H2S during the pathogenesis of colitis have not been established. We analyzed the contribution of H2S to inflammation and ulceration of the colon in a rat model OF colitis. METHODS: Colitis was induced by intracolonic administration of trinitrobenzene sulfonic acid. The ability of the colon to synthesize H2S Was Studied over the course of the resolution of the colitis. Expression of 2 enzymes involved in the synthesis of H2S and the effects of inhibitors of these enzymes were examined. We also examined the effects of H2S donors on the resolution of colitis. RESULTS: The capacity for the colon to produce H2S increased markedly over the first days after induction of colitis and then declined toward control levels as the colitis was resolved. inhibition of colonic H2S synthesis markedly exacerbated the colitis, resulting in significant mortality. Inhibition of H2S synthesis in healthy rats resulted in inflammation and mucosal injury in the small intestine and colon along with down-regulation of cyclooxygenase-2 messenger RNA expression and prostaglandin synthesis. Intracolonic administration of H2S donors significantly reduced the severity of colitis and reduced colonic expression of messenger RNA for the proinflammatory cytokine tumor necrosis factor a. CONCLUSIONS: In rats, H2S modulates physiological inflammation and contributes to the resolution of colitis.