title: Irsogladine maleate ameliorates inflammation and fibrosis in mice with chronic colitis induced by dextran sulfate sodium.
abstract: Intestinal fibrosis is a common and severe complication of inflammatory bowel disease (IBD), especially Crohn's disease (CD). To investigate the therapeutic approach to intestinal fibrosis, we have developed a mouse model of intestinal fibrosis by administering dextran sulfate sodium (DSS) and examining the effects of irsogladine maleate (IM) [2,4-diamino-6-(2,5-dichlorophenyl)-s-triazine maleate], which has been widely used as an antiulcer drug for gastric mucosa in Japan, on DDS-induced chronic colitis. In this experimental colitis lesion, several pathognomonic changes were found: increased deposition of collagen, increased number of profibrogenic mesenchymal cells such as fibroblasts (vimentin(+), α-SMA(-)) and myofibroblasts (vimentin(+), α-SMA(+)) in both mucosa and submucosa of the colon with infiltrating inflammatory cells, and increased mRNA expressions of collagen type I, transforming growth factor (TGF)-β, matrix metalloproteinase (MMP)-2, and tissue inhibitor of matrix metalloproteinase (TIMP)-1. When IM was administered intrarectally to this colitis, all these pathological changes were significantly decreased or suppressed, suggesting a potential adjunctive therapy for intestinal fibrosis. IM could consequently reduce fibrosis in DSS colitis by direct or indirect effect on profibrogenic factors or fibroblasts. Therefore, the precise effect of IM on intestinal fibrosis should be investigated further.
authors.affiliation: Department of Gastroenterology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Hana
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Kenji
authors.initials: K
authors.lastname: Suzuki
authors.forename: Masaki
authors.initials: M
authors.lastname: Nagata
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kawase
authors.forename: Vijayakumar
authors.initials: V
authors.lastname: Sukumaran
authors.forename: Rajarajan A
authors.initials: RA
authors.lastname: Thandavarayan
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kawauchi
authors.forename: Junji
authors.initials: J
authors.lastname: Yokoyama
authors.forename: Masayuki
authors.initials: M
authors.lastname: Tomita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawachi
authors.forename: Kenichi
authors.initials: K
authors.lastname: Watanabe
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoneyama
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Asakura
authors.forename: Ritsuo
authors.initials: R
authors.lastname: Takagi
mesh_terms: D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002908:Chronic Disease; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016896:Treatment Outcome; D014227:Triazines / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000897:Anti-Ulcer Agents; D014227:Triazines; D016264:Dextran Sulfate; C041836:irsogladine