Endogenous Hydrogen Sulfide Is an Anti-inflammatory Molecule in Dextran Sodium Sulfate-Induced Colitis in Mice
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Ikuhiro Hirata Yuji Naito Tomohisa Takagi Katsura Mizushima Takahiro Suzuki Tatsushi Omatsu Osamu Handa Hiroshi Ichikawa Hideo Ueda
- چاپ و سال / کشور: 2010
Description
Background Endogenous hydrogen sulfide (H2S) is increasingly being recognized as an important gaseous physiological mediator. Accumulating evidence shows the functions of H2S in various models of disease, but rarely in colitis. In this study, we investigated the role of endogenous H2S in a dextran sodium sulfate (DSS)-induced colitis model. Methods Acute colitis was induced using 8% DSS in male BALB/c mice. The mRNA expression of cystathionine clyase (CSE), the primary synthetase of H2S in the gastrointestinal tract, and cystathionine-b-synthetase (CBS) was measured by real-time RT-PCR. The amount of H2S in the colonic mucosa was measured by gas chromatography. Colitis severity was evaluated clinically, histologically, and biochemically under the condition of co-treatment with DLpropargylglycine (PAG), an irreversible CSE inhibitor, and sodium sulfide (Na2S), an H2S donor. Results The mRNA expression levels of CSE and CBS, and the H2S content in the colonic mucosa were increased with time after DSS administration. The disease activity index, which was determined by weight loss, stool consistency, and intestinal bleeding, increased after DSS administration. PAG significantly enhanced the increase in the disease activity index scores. PAG also significantly increased tissue-associated myeloperoxidase activity and thiobarbituric acid-reactive substances in the inflamed mucosa. Moreover, Na2S counteracted these effects of PAG. Conclusions Taken together, the results indicated that the inhibition of endogenous H2S generation caused the deterioration of DSS-induced colitis. We conclude that physiological H2S might act as an anti-inflammatory molecule in colitis.
Dig Dis Sci (2011) 56:1379–1386 DOI 10.1007/s10620-010-1461-5 Received: 8 May 2010 / Accepted: 6 October 2010 / Published online: 28 October 2010
