title: Prophylactic effect of rebamipide on aspirin-induced gastric lesions and disruption of tight junctional protein zonula occludens-1 distribution.
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.
authors: Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan.
authors: Takahiro
authors: T
authors: Suzuki
authors: Norimasa
authors: N
authors: Yoshida
authors: Nami
authors: N
authors: Nakabe
authors: Yutaka
authors: Y
authors: Isozaki
authors: Hirokazu
authors: H
authors: Kajikawa
authors: Tomohisa
authors: T
authors: Takagi
authors: Osamu
authors: O
authors: Handa
authors: Satoshi
authors: S
authors: Kokura
authors: Hiroshi
authors: H
authors: Ichikawa
authors: Yuji
authors: Y
authors: Naito
authors: Hirofumi
authors: H
authors: Matsui
authors: Toshikazu
authors: T
authors: Yoshikawa
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001241:Aspirin / Q000633:toxicity*; D002460:Cell Line; D019610:Cytoprotection; D005455:Fluorescent Antibody Technique; D005753:Gastric Mucosa / Q000187:drug effects*; D008297:Male; D008565:Membrane Proteins / Q000032:analysis*; D010539:Permeability; D010750:Phosphoproteins / Q000032:analysis*; D015363:Quinolones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D062826:Zonula Occludens-1 Protein
chemical_list: D000897:Anti-Ulcer Agents; D008565:Membrane Proteins; D010750:Phosphoproteins; D015363:Quinolones; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; C052785:rebamipide; D000409:Alanine; D001241:Aspirin