title: Ecabet sodium promotes the healing of trinitrobenzene-sulfonic-acid-induced ulceration by enhanced restitution of intestinal epithelial cells.
abstract: OBJECTIVE
  Ecabet sodium (ES) is a gastric mucosal protective and ulcer-healing agent. Recently enema therapy with ES was found to be effective for the treatment of human ulcerative colitis as well as experimental colitis in an animal model. Whereas ES possesses potential as a novel treatment for ulcerative colitis, its precise mechanism of action remains to be elucidated. In this study, we investigated the therapeutic efficacy of ES in an experimental rat model of colitis, and evaluated the restitution of intestinal epithelial cells treated with ES in vitro.
  
  
  METHODS
  Acute colitis was induced with trinitrobenzene sulfonic acid (TNBS) in male Wistar rats. Rats received intrarectal treatment with ES daily starting on day 7 and were sacrificed on day 14 after the administration of TNBS. The distal colon was removed to evaluate various parameters of inflammation. Moreover, wound-healing assays were used to determine the enhanced restitution of rat intestinal epithelial (RIE) cells treated with ES.
  
  
  RESULTS
  Intracolonic administration of ES accelerated TNBS-induced ulcer healing. Increases in the wet weight of the colon after TNBS administration were significantly inhibited by ES treatment. The wound assay revealed ES enhancement of the migration of RIE cells migration through the phosphorylation of extracellular signal-regulated kinase.
  
  
  CONCLUSIONS
  Daily administration of an ES enema promoted the healing of intestinal mucosal injury, in part by the enhanced restitution of intestinal epithelial cells via extracellular signal-regulated kinase activation. ES may thus represent a novel therapeutic approach for the treatment of inflammatory bowel disease.
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Takagi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Naito
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Okuda
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Uchiyama
authors.forename: Satoko
authors.initials: S
authors.lastname: Adachi
authors.forename: Katsura
authors.initials: K
authors.lastname: Mizushima
authors.forename: Osamu
authors.initials: O
authors.lastname: Handa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kokura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ichikawa
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D045784:Abietanes / Q000008:administration & dosage / Q000494:pharmacology*; D000208:Acute Disease; D000285:Administration, Rectal; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D003106:Colon / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D004195:Disease Models, Animal; D004733:Enema; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014302:Trinitrobenzenesulfonic Acid; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D045784:Abietanes; D000897:Anti-Ulcer Agents; C061681:ecabet; D014302:Trinitrobenzenesulfonic Acid; D048049:Extracellular Signal-Regulated MAP Kinases