Protective effect of rebamipide on indomethacin-induced intestinal damage in rats

Hiroyuki Mizoguchi, Yoshihiro Ogawa, Kenji Kanatsu, Akiko Tanaka, Shinichi Kato, Koji Takeuchi

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Background and Aim: We evaluated the effect of rebamipide (2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl] propionic acid), a novel anti-ulcer drug, on indomethacin-induced small intestinal lesions in rats. Methods: The animals were administered indomethacin (10 mg/kg, s.c.), and they were killed 24 h later. Rebamipide (30-300 mg/kg) was administered p.o. twice, 30 min before, and 6 h after indomethacin. Results: Indomethacin caused hemorrhagic lesions in the rat small intestine, accompanied by an increase in enterobacterial translocation, inducible nitric oxide synthase (iNOS) and myeloperoxidase (MPO) activities, as well as thiobarbituric acid (TBA) reactants, and these changes were significantly prevented by the supplementation with 16,16-dimethyl prostaglandin E2 (dmPGE2; 10 μg/kg, i.v.) or the pretreatment of animals with the antibiotic ampicillin. Treatment of the animals with rebamipide dose-dependently prevented the development of intestinal lesions, and this effect was mimicked by i.v. administration of superoxide dismutase (SOD: 3000 U/kg) + catalase (CAT: 5000 U/kg). The protection by rebamipide was accompanied by a significant suppression of the increase in both MPO and iNOS activities, and a complete inhibition of the increase in TBA reactants, while SOD + CAT significantly inhibited the increase of MPO activity and TBA reactants, but not iNOS activity. The bacterial translocation following indomethacin was also significantly decreased by either rebamipide or SOD + CAT. Conclusion: These results confirmed the importance of enterobacteria and iNOS/NO in the pathogenesis of indomethacin-induced small intestinal lesions, and suggested that rebamipide prevents the development of these lesions, probably by its radical scavenging action.

Original languageEnglish
Pages (from-to)1112-1119
Number of pages8
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume16
Issue number10
DOIs
Publication statusPublished - Jan 1 2001
Externally publishedYes

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Indomethacin
Nitric Oxide Synthase Type II
Peroxidase
Anti-Ulcer Agents
Bacterial Translocation
Enterobacteriaceae
Ampicillin
rebamipide
Dinoprostone
Catalase
Superoxide Dismutase
Small Intestine
Anti-Bacterial Agents
thiobarbituric acid

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Cite this

Protective effect of rebamipide on indomethacin-induced intestinal damage in rats. / Mizoguchi, Hiroyuki; Ogawa, Yoshihiro; Kanatsu, Kenji; Tanaka, Akiko; Kato, Shinichi; Takeuchi, Koji.

In: Journal of Gastroenterology and Hepatology (Australia), Vol. 16, No. 10, 01.01.2001, p. 1112-1119.

Research output: Contribution to journalArticle

Mizoguchi, Hiroyuki ; Ogawa, Yoshihiro ; Kanatsu, Kenji ; Tanaka, Akiko ; Kato, Shinichi ; Takeuchi, Koji. / Protective effect of rebamipide on indomethacin-induced intestinal damage in rats. In: Journal of Gastroenterology and Hepatology (Australia). 2001 ; Vol. 16, No. 10. pp. 1112-1119.
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