Endogenous hydrogen sulfide is an anti-inflammatory molecule in dextran sodium sulfate-induced colitis in mice.

Ikuhiro Hirata, Yuji Naito, Tomohisa Takagi, Katsura Mizushima, Takahiro Suzuki, Tatsushi Omatsu, Osamu Handa, Hiroshi Ichikawa, Hideo Ueda, Toshikazu Yoshikawa

Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.

Digestive diseases and sciences 2011 May

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Endogenous hydrogen sulfide (H(2)S) is increasingly being recognized as an important gaseous physiological mediator. Accumulating evidence shows the functions of H(2)S in various models of disease, but rarely in colitis. In this study, we investigated the role of endogenous H(2)S in a dextran sodium sulfate (DSS)-induced colitis model. Acute colitis was induced using 8% DSS in male BALB/c mice. The mRNA expression of cystathionine γ-lyase (CSE), the primary synthetase of H(2)S in the gastrointestinal tract, and cystathionine-β-synthetase (CBS) was measured by real-time RT-PCR. The amount of H(2)S in the colonic mucosa was measured by gas chromatography. Colitis severity was evaluated clinically, histologically, and biochemically under the condition of co-treatment with DL-propargylglycine (PAG), an irreversible CSE inhibitor, and sodium sulfide (Na(2)S), an H(2)S donor. The mRNA expression levels of CSE and CBS, and the H(2)S 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, Na(2)S counteracted these effects of PAG. Taken together, the results indicated that the inhibition of endogenous H(2)S generation caused the deterioration of DSS-induced colitis. We conclude that physiological H(2)S might act as an anti-inflammatory molecule in colitis.

Citation

Ikuhiro Hirata, Yuji Naito, Tomohisa Takagi, Katsura Mizushima, Takahiro Suzuki, Tatsushi Omatsu, Osamu Handa, Hiroshi Ichikawa, Hideo Ueda, Toshikazu Yoshikawa. Endogenous hydrogen sulfide is an anti-inflammatory molecule in dextran sodium sulfate-induced colitis in mice. Digestive diseases and sciences. 2011 May;56(5):1379-86