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  • Title: Protective effect and mechanism of rebamipide on NSAIDs associated small bowel injury.
    Author: Xu N, Zhang C, Jing L, Mou S, Cao X, Yu Z.
    Journal: Int Immunopharmacol; 2021 Jan; 90():107136. PubMed ID: 33218942.
    Abstract:
    PURPOSE: To investigate the protective effect and mechanism of rebamipide on NSAIDs associated intestinal injury. METHODS: Intestinal injury was induced in Sprague Dawley rats by intragastric administration of diclofenac with rebamipide intervention, and LPS and TAK-242 were given intraperitoneally respectively. The expression of TLR4/NF-κB and the related proteins in the intestinal mucosa were detected. 55 patients taking NSAIDs and diagnosed as NSAIDs associated small intestinal injury were recruited as NSAIDs group. Another 55 patients without NSAIDs and no obvious abnormality in the small bowel served as the control group. RESULTS: The macroscopic and histological scores of the small intestinal mucosa in the rebamipide pretreatment group were significantly lower compared to the diclofenac group (p < 0.01). The expressions of Tollip, ZO-1 and Claudin-1 in the diclofenac group were down-regulated compared with that in the control group, while they increased significantly in the rebamipide pretreatment group (p < 0.01). The expressions of TLR4/NF-κBp65, IL-1β, IL-6, IL-8, and TNF-α significantly increased in the model group while they were down-regulated in the rebamipide pretreatment group (p < 0.05). Administration of LPS 1 h after diclofenac aggravated small intestinal damage, and increased expression of IL-1β, IL-6, IL-8 and TNF-α. Administration of rebamipide did not effectively reverse intestinal injury induced by diclofenac and LPS. In contrast, pretreatment with TAK-242 significantly inhibited damage and prevented the increased expression of the cytokines. The expression of TLR4 and NF-κBp65 in the patients with NSAIDs associated intestinal injury was significantly higher than that in the control group (p < 0.01), while the expression of Tollip was decreased (p < 0.01). CONCLUSION: Rebamipide effectively alleviated intestinal mucosa injury by probably suppressing the TLR4/NF-κB signaling pathway and the decreasing of ZO-1 and Claudin-1 induced by diclofenac.
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