title: Endogenous hydrogen sulfide is an anti-inflammatory molecule in dextran sodium sulfate-induced colitis in mice.
abstract: 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.
authors.affiliation: Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Ikuhiro
authors.initials: I
authors.lastname: Hirata
authors.forename: Yuji
authors.initials: Y
authors.lastname: Naito
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Takagi
authors.forename: Katsura
authors.initials: K
authors.lastname: Mizushima
authors.forename: Takahiro
authors.initials: T
authors.lastname: Suzuki
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Omatsu
authors.forename: Osamu
authors.initials: O
authors.lastname: Handa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ichikawa
authors.forename: Hideo
authors.initials: H
authors.lastname: Ueda
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: 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
chemical_list: 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