Revaprazan prevented indomethacin-induced intestinal damages by enhancing tight junction related mechanisms.

We examined intestinal permeability-related molecular changes in in vitro Caco-2 cell models and in an in vivo indomethacin-induced enteropathy rat model. Indomethacin alone or in combination with pantoprazole significantly increased relative lucifer yellow dye flux and decreased relative trans-epithelial electrical resistance and tight junction protein (TJP) expression compare to normal cells. In contrast, indomethacin combined with revaprazan significantly preserved TJPs compare to indomethacin-treated cells. MLC phosphorylation, Rho activation, and ERK activation responsible for TJP were significantly increased by indomethacin alone or a combination of indomethacin and pantoprazole but not by a combination of indomethacin and revaprazan. Intestinal damage scores significantly increased with indomethacin and pantoprazole combination but not with indomethacin and revaprazan combination. Indomethacin and pantoprazole combination significantly activated Rho-GTPase, p-MLC, and p-ERK but significantly decreased TJP expression. However, indomethacin and revaprazan combination significantly preserved TJPs and inactivated Rho-GTPase, MLC, and ERK. Hence, revaprazan rather than PPIs should be co-administered with NSAIDs to mitigate NSAID-induced intestinal damage. PMID: 33075311 [PubMed - as supplied by publisher]
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research