title: Nafamostat mesilate attenuates colonic inflammation and mast cell infiltration in the experimental colitis.
abstract: Serine proteases are important in the pathogenesis of intestinal inflammation. Recent studies have shown that nafamostat mesilate (NM) can inhibit the colonic mucosal inflammation induced by TNBS in rats. The aim of this study was to investigate the anti-inflammatory effects of NM on a DSS-induced colitis. Colitis was induced in female BALB/c mice by 5% dextran sulfate sodium (DSS) for 6 days. NM (2 or 20mg/kg body weight) was orally administered once a day for 6 days during treatment of the mice with DSS. The inflammatory response of the colon was assessed 1 week after DSS treatment. NM at a high dose, but not at a low dose significantly decreased disease activity index (DAI) and myeloperoxidase (MPO) induced by DSS. Furthermore, NM (20mg/kg) inhibited the production of tumor necrosis factor (TNF)-α, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in the colonic tissues treated with DSS. The increase in chymase activity by DSS treatment was also attenuated by the administration of NM (20mg/kg). NM (20mg/kg) significantly decreased the colonic mucosal injury and the infiltrated mast cell number induced by DSS. These results indicate that NM might inhibit the colonic inflammation through inhibition of both chymase activity and mast cell infiltration in colon tissues of DSS-induced colitis.
authors.affiliation: Digestive Disease Research Institute and Wonkwang University School of Medicine, Iksan, Jeonbuk 570-749, Republic of Korea.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Cho
authors.forename: Suck-Chei
authors.initials: SC
authors.lastname: Choi
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Ahn
authors.forename: Lee-Rang
authors.initials: LR
authors.lastname: Im
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: Kim
authors.forename: Mingjie
authors.initials: M
authors.lastname: Xin
authors.forename: Se-Uk
authors.initials: SU
authors.lastname: Kwon
authors.forename: Dae-Ki
authors.initials: DK
authors.lastname: Kim
authors.forename: Young-Mi
authors.initials: YM
authors.lastname: Lee
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D001550:Benzamidines; D015153:Blotting, Western; D002452:Cell Count; D053818:Chymases / Q000378:metabolism; D003092:Colitis / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006146:Guanidines / Q000008:administration & dosage / Q000627:therapeutic use*; D018928:Immunity, Mucosal / Q000187:drug effects; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009195:Peroxidase / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001550:Benzamidines; D006146:Guanidines; D009195:Peroxidase; D053818:Chymases; C032855:nafamostat