RRC ID 43311
著者 Suzuki T, Yoshida N, Nakabe N, Isozaki Y, Kajikawa H, Takagi T, Handa O, Kokura S, Ichikawa H, Naito Y, Matsui H, Yoshikawa T.
タイトル Prophylactic effect of rebamipide on aspirin-induced gastric lesions and disruption of tight junctional protein zonula occludens-1 distribution.
ジャーナル J Pharmacol Sci
Abstract Aspirin and nonsteroidal anti-inflammatory agents are known to induce gastroduodenal complications such as ulcer, bleeding, and dyspepsia. In this study, we examined the prophylactic effect of rebamipide, an anti-ulcer agent with free-radical scavenging and anti-inflammatory effect, on acidified aspirin-induced gastric mucosal injury in rats. In addition, we investigated the mucosal barrier functions disrupted by aspirin. Oral administration of acidified aspirin resulted in linear hemorrhagic erosions with increasing myeloperoxidase activity and thiobarbituric acid-reactive substance concentrations in the gastric mucosa. Rebamipide suppressed these acidified aspirin-induced gastric lesions and inflammatory changes significantly, and its protective effect was more potent in the case of repeated (twice daily for 3 days) treatment than single treatment before aspirin administration. Immunostaining of zonula occludens (ZO)-1, one of the tight junctional proteins, was strengthened in rat gastric mucosa after repeated administration of rebamipide. In addition, aspirin induced the increasing transport of fluorescine isothiocyanate-labeled dextrans with localized disruption and decreased expression of ZO-1 protein on rat gastric mucosal cell line RGM-1. Rebamipide effectively prevented aspirin-induced permeability changes and disruption of ZO-1 distribution. These results suggest that rebamipide protects against aspirin-induced gastric mucosal lesions by preserving gastric epithelial cell-to cell integrity in addition to the anti-inflammatory effects.
巻・号 106(3)
ページ 469-77
公開日 2008-3-1
DOI 10.1254/jphs.fp0071422
PII JST.JSTAGE/jphs/FP0071422
PMID 18360096
MeSH Alanine / analogs & derivatives* Alanine / pharmacology Animals Anti-Ulcer Agents / pharmacology* Aspirin / toxicity* Cell Line Cytoprotection Fluorescent Antibody Technique Gastric Mucosa / drug effects* Male Membrane Proteins / analysis* Permeability Phosphoproteins / analysis* Quinolones / pharmacology* Rats Rats, Sprague-Dawley Zonula Occludens-1 Protein
IF 2.835
引用数 25
WOS 分野 PHARMACOLOGY & PHARMACY
リソース情報
ヒト・動物細胞 RGM1(RCB0876)