title: Rebamipide attenuates indomethacin-induced gastric mucosal lesion formation by inhibiting activation of leukocytes in rats.
abstract: Granulocyte elastase released from activated leukocytes plays an important role in leukocyte infiltration. Since activated leukocytes have been shown to be involved in the pathogenesis of gastric mucosal lesion formation induced by nonsteroidal antiinflammatory drugs, inhibition of granulocyte elastase release from activated leukocytes may be useful in the prevention of these lesions. Rebamipide, a novel antiulcer agent, inhibited granulocyte elastase release from activated neutrophils in vitro. Rebamipide and ONO-5046, a granulocyte elastase inhibitor, markedly inhibited gastric mucosal lesion formation in rats. Gastric myeloperoxidase activity was significantly increased 3 hr after indomethacin administration. This increase was significantly inhibited by rebamipide and ONO-5046. Cimetidine did not inhibit granulocyte elastase release from activated neutrophils. Although cimetidine markedly prevented the indomethacin-induced gastric mucosal lesion formation, it did not reduce the gastric myeloperoxidase activity. Therefore, unlike cimetidine, rebamipide may prevent indomethacin-induced gastric mucosal lesion formation by inhibiting neutrophil activation.
authors.affiliation: Department of Medicine, Kumamoto University Medical School, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Murakami
authors.forename: K
authors.initials: K
authors.lastname: Okajima
authors.forename: M
authors.initials: M
authors.lastname: Uchiba
authors.forename: N
authors.initials: N
authors.lastname: Harada
authors.forename: M
authors.initials: M
authors.lastname: Johno
authors.forename: H
authors.initials: H
authors.lastname: Okabe
authors.forename: K
authors.initials: K
authors.lastname: Takatsuki
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002927:Cimetidine / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000633:toxicity*; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D015363:Quinolones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D015363:Quinolones; D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; D002927:Cimetidine; C069195:sivelestat; D009195:Peroxidase; D019272:Leukocyte Elastase; C052785:rebamipide; D000409:Alanine; D005998:Glycine; D007213:Indomethacin