Rebamipide Promotes the Regeneration of Aspirin-Induced Small-Intestine Mucosal Injury through Accumulation of β-Catenin

Abstract

BackgroundThe effect of rebamipide on repairing intestinal mucosal damage induced by nonsteroidal anti-inflammatory drugs and its mechanism remain unclear. In this study, we sought to explore the mechanism whereby rebamipide could promote the regeneration of aspirin-induced intestinal mucosal damage.MethodsBALB/c mice were administered aspirin (200 mg/kg/d) for 5 days to induce acute small intestinal injury (SII). Subsequently, SII mice were treated with rebamipide (320 mg/kg/d) for 5 days. The structure of intestinal barrier was observed with transmission electron microscope, and Zo-1 and occludin expressions were detected. The proliferative index was indicated by the percentage of proliferating cell nuclear antigen positive cells. The prostaglandin E2 (PGE2) levels in the small intestine tissues were measured by an enzyme immunoassay. The mRNA and protein expression levels of cyclooxygenase (COX) and β-catenin signal were detected in the small intestine using quantitative PCR and Western blot, respectively.ResultsCOX expression was significantly down-regulated in aspirin induced SII (P < 0.05). In SII mice treated with rebamipide, histopathological findings of aspirin-induced intestinal inflammation were significantly milder and tight junctions between intestinal epithelial cells were improved significantly. The proliferative index increased after rebamipide treatment when compared with that in the control mice. The expressions of COX-2, β-catenin, and c-myc and the PGE2 concentrations in small intestinal tissues were significantly increased in mice with rebamipide treatments (P < 0.05).ConclusionRebamipide administration in aspirin-induced SII mice could improve the intestinal barrier structure and promote the regeneration of small intestinal epithelial injury through up-regulating COX-2 expression and the accumulation of β-catenin.

Rebamipide alleviates radiation‐induced colitis through improvement of goblet cell differentiation in mice

“…To investigate the effects of rebamipide on the intestine, we used abdominal irradiation for mice to reduce the radiationinduced bone marrow injury. There are many reports of therapeutic effects of rebamipide on small intestinal injury [22][23][24] ; however, reports related to radiation-induced colonic injury are limited. Colitis is a clinical side effect of radiotherapy, which involves the gut microflora and induces colonic endotoxemia.…”

“…21 Application of rebamipide alleviates the inflammation in the small intestine through its anti-inflammatory effects and activation of the Wnt/β-catenin pathway. 22,23 In this study, because goblet cells play important roles in intestinal barrier damage, we investigated whether rebamipide could attenuate the radiation-induced colitis by inducing differentiation of goblet cells in mice model and human colonic epithelial cell line.…”

Bifidobacterium breve Bif195 Protects Against Small-Intestinal Damage Caused by Acetylsalicylic Acid in Healthy Volunteers

“…7,8 Besides the well-established inhibitory effect of cyclooxygenase (COX), ASA specifically has been recognized to compromise the phospholipid layer in mucus, 11 increasing access to luminal aggressors like lipopolysaccharide and bile, as well as disrupting intestinal permeability and causing inflammation. 12 Given that deleterious compositional changes to the microbiota, in addition to direct effects on mucus and epithelial tissue, may increase the risk of NSAID enteropathy, we hypothesized that an intervention targeting microbiome-host interactions may offer an attractive preventative strategy. Our strain selection was based on the anti-inflammatory properties of certain bifidobacteria 13,14 and experimental preclinical evidence for a role of bifidobacteria in NSAID-associated ulceration, [15][16][17] as well as unpublished preclinical screening data suggesting a particular potential of efficacy for the specific strain belonging to this genus.…”

Yogurt Containing <b><i>Lactobacillus gasseri</i></b> Mitigates Aspirin-Induced Small Bowel Injuries: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial

“…Furthermore, Watanabe et al [17] conducted a multicenter, randomized, double-blind, placebo-controlled trial to assess the efficacy of rebamipide in patients taking enteric-coated LDA for more than 3 months, and reported that rebamipide, but not placebo, significantly decreased the number of mucosal breaks after 8 weeks of treatment. Lai et al [23] explored the mechanism by which rebamipide promoted the regeneration of aspirin-induced intestinal mucosal damage and reported that the drug could strengthen tight junctions between intestinal epithelial cells and increase COX-2, β-catenin, and PGE2 expression in small intestinal tissues. Watanabe et al [19] also reported the efficacy of misoprostol in the treatment of LDA-induced small bowel mucosal injuries such as red spots and mucosal breaks in patients taking enteric-coated aspirin in a pilot study.…”