Endogenous and exogenous hydrogen sulfide promotes resolution of colitis in rats.
OBJECTIVE
Hydrogen sulfide (H(2)S) is an endogenous gaseous mediator of mucosal defense with antiinflammatory effects that promote ulcer healing. The effects of H(2)S during the pathogenesis of colitis have not been established. We analyzed the contribution of H(2)S 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 H(2)S was studied over the course of the resolution of the colitis. Expression of 2 enzymes involved in the synthesis of H(2)S and the effects of inhibitors of these enzymes were examined. We also examined the effects of H(2)S donors on the resolution of colitis.


RESULTS
The capacity for the colon to produce H(2)S increased markedly over the first days after induction of colitis and then declined toward control levels as the colitis was resolved. Inhibition of colonic H(2)S synthesis markedly exacerbated the colitis, resulting in significant mortality. Inhibition of H(2)S 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 H(2)S donors significantly reduced the severity of colitis and reduced colonic expression of messenger RNA for the proinflammatory cytokine tumor necrosis factor alpha.


CONCLUSIONS
In rats, H(2)S modulates physiological inflammation and contributes to the resolution of colitis.
Inflammation Research Network, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada. jwalla@mcmaster.ca
John L
JL
Wallace
Linda
L
Vong
Webb
W
McKnight
Michael
M
Dicay
Gary R
GR
Martin
D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001707:Biopsy, Needle; D003092:Colitis / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000473:pathology*; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D005905:Glyburide / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000378:metabolism* / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D020110:Pinacidil / Q000494:pharmacology; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D015996:Survival Rate; D016896:Treatment Outcome; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism
D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D020110:Pinacidil; D014302:Trinitrobenzenesulfonic Acid; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D005905:Glyburide; D006862:Hydrogen Sulfide