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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Hirata
Ikuhiro
I
Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
Naito
Yuji
Y
Takagi
Tomohisa
T
Mizushima
Katsura
K
Suzuki
Takahiro
T
Omatsu
Tatsushi
T
Handa
Osamu
O
Ichikawa
Hiroshi
H
Ueda
Hideo
H
Yoshikawa
Toshikazu
T
D000480:Alkynes / Q000494:pharmacology; D000818:Animals; D003092:Colitis / Q000139:chemically induced* / Q000378:metabolism*; D003541:Cystathionine beta-Synthase / Q000235:genetics / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000235:genetics / Q000378:metabolism; D016264:Dextran Sulfate / Q000633:toxicity*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013431:Sulfates / Q000494:pharmacology; D013997:Time Factors
D000480:Alkynes; D012333:RNA, Messenger; D013431:Sulfates; C012036:sodium sulfate; C009055:propargylglycine; D016264:Dextran Sulfate; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; D005998:Glycine; D006862:Hydrogen Sulfide