H₂S confers colonoprotection against TNBS-induced colitis by HO-1 upregulation in rats

Hydrogen sulfide (H₂S) is an endogenous mediator that contributes to many important physiological processes including vasodilation and vascular smooth muscle relaxation; in turn, preventing tissue damage and reducing inflammation. Heme oxygenase (HO) enzymes, of which HO-1 is inducible by harmful stimuli, were found to regulate intestinal inflammation in experimental animal models of colitis. We aimed to investigate the protective effects of H₂S against 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats, and whether HO enzyme system is involved in the H₂S-induced colonic cytoprotection. Male Wistar rats were treated with TNBS to induce colitis, and H₂S donor (Lawesson's reagent) was prepared two times/day at different concentrations, and delivered per os (from day 1 to day 3). Our results suggest that daily treatment (2 times/day) with H₂S donor, could significantly decrease the extent of colonic inflammation compared to vehicle treatment, and the most effective daily dose of H₂S donor against inflammation was 18.75 µM/kg/day. Per os administration of H₂S donor increased the colonic HO enzyme activity; on the contrary, the protective effect of H₂S was abolished by the co-treatment with HO inhibitor. Our findings suggest that H₂S confers colonoprotection, probably by modulation of anti-inflammatory parameters and HO enzyme activity.