Prophylactic Effect of Rebamipide on Aspirin-Induced Gastric Lesions and Disruption of Tight Junctional Protein Zonula Occludens-1 Distribution

Abstract

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 antiinflammatory 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.

Increase of Faecal Tryptic Activity Relates to Changes in the Intestinal Microbiome: Analysis of Crohn's Disease with a Multidisciplinary Platform

“…It has been shown in conventional mice that intra-colonic administration of trypsin cause mucosal damage [29] whereas high levels of intra-colonic trypsin in germfree animals never trigger any mucosal damages [4], [30], [31], [32], [33], [34]. Obviously, there is a need for “trigger” microbe(s) or mechanism(s).…”

A randomized, double-blinded, placebo-controlled, multicenter trial, healing effect of rebamipide in patients with low-dose aspirin and/or non-steroidal anti-inflammatory drug induced small bowel injury

“…Long-term use of LDA and/or NSAID leads to hyper-permeation of small intestinal mucosa [10]. Moreover, chronic hyper-permeation in the small intestinal mucosa leads to rhexis of tight junction [15]. On the other hand, reducing prostaglandin leads to decreasing of blood flow [16].…”

Sodium Cromoglycate Prevents Exacerbation of IgE-Mediated Food-Allergic Reaction Induced by Aspirin in a Rat Model of Egg Allergy

“…Matsubara et al [45] reported that intact (45 kDa) and truncated (40 kDa) forms of OVA were detected in portal and peripheral blood after oral administration, indicating that OVA absorbed into blood from the intestinal lumen possesses its allergenicity. With regard to the mechanism of ASP-induced intestinal barrier disruption, suppression of prostaglandin synthesis by COX-1 [46] , oxidative stress [47] , and modulation of tight junctional proteins such as zonula occludens (ZO)-1 [48] and claudin-7 [49] have been reported. The specific sensitization is known to increase intestinal absorption of the allergen in several animal models of allergy [50][51][52][53][54] .…”