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: Hana Yamaguchi, Kenji Suzuki, Masaki Nagata, Tomoyuki Kawase, Vijayakumar Sukumaran, Rajarajan A Thandavarayan, Yusuke Kawauchi, Junji Yokoyama, Masayuki Tomita, Hiroshi Kawachi, Kenichi Watanabe, Hiroyuki Yoneyama, Hitoshi Asakura, Ritsuo Takagi
• Journal: Medical molecular morphology (Med Mol Morphol) Vol. 45 Issue 3 Pg. 140-51 (Jun 2012) ISSN: 1860-1499 [Electronic] Japan
• PMID: 23001296 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Ulcer Agents
• Triazines
• Dextran Sulfate
• irsogladine

Topics

• Animals
• Anti-Ulcer Agents (administration & dosage, therapeutic use)
• Chronic Disease
• Colitis (chemically induced, drug therapy, metabolism, pathology)
• Dextran Sulfate
• Disease Models, Animal
• Female
• Fibrosis (drug therapy, metabolism, pathology)
• Humans
• Inflammation (drug therapy, metabolism, pathology)
• Intestinal Mucosa (metabolism, pathology)
• Mice
• Mice, Inbred C57BL
• Treatment Outcome
• Triazines (administration & dosage, therapeutic use)