Altered response to hydrogen sulphide during experimental colitis in rats

Hydrogen sulphide (H₂S) is produced in the intestine by sulphate‐reducing bacteria and during metabolism of L‐cysteine within the mucosa. This gasotransmitter induces anion secretion by stimulating enteric neurons and by a direct effect on epithelial cells. As H₂S is discussed to exert both pro‐ and anti‐inflammatory actions, we aimed to investigate the role of H₂S during experimental colitis by comparing the effects of blockade of H₂S‐forming endogenous enzymes with the effect of a S‐reduced diet to diminish microbial production of H₂S. Rectal application of trinitrobenzenesulfonic acid (TNBS) was used to induce chronic colitis. The level of inflammation was assessed macroscopically and histologically. In Ussing chamber experiments, colonic specimens from TNBS‐treated animals exhibited a higher tissue conductance, that is, a higher epithelial permeability, and a slightly reduced basal short‐circuit current (a measure of net ion transport) in relation to non‐inflamed control tissue. Analgetic treatment with flupirtine, a central antinociceptive analgetic, did not interfere with the induction of the inflammatory response so that all animals were treated with flupirtine to reduce pain and distress during the development of colitis. The secretory response evoked by an exogenous H₂S donor, NaHS, was significantly decreased after induction of colitis, whereas the response to Ca²⁺‐ or cAMP‐dependent secretagogues was unaltered. This downregulation was not observed in the colitis group fed on a S‐reduced diet. The decreased NaHS response indicates a desensitization of the tissue by inflammation, which might be explained by an upregulation of colonic H₂S production as described in some models of inflammation.