Journal
KOREAN JOURNAL OF GASTROENTEROLOGY
Volume 79, Issue 4, Pages 161-169Publisher
Korean Soc Gastroenterology
DOI: 10.4166/kjg.2022.003
Keywords
Gastritis; Ethanol; Anti-inflammatory agents; non-steroidal; Mice; Ursodoxicoltaurine
Categories
Funding
- Seoul Metropolitan Government Seoul National University (SMG-SNU) Boramae Medical Center [01-2014-22]
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Tauroursodeoxycholic acid (TUDCA) protects gastric epithelial cells by inhibiting NF-kappa B signaling and ameliorating ethanol- and NSAID-induced gastritis.
Background/Aims: Previous studies have reported the protective effects of tauroursodeoxycholic acid (TUDCA) on gastric epithelial cells in some animal models, but the precise mechanisms are unclear. This study examined the effects of TUDCA on NF-kappa B signaling in gastric epithelial cells. Moreover, the protective effects of TUDCA in experimental gastritis models induced by ethanol and NSAID were evaluated and compared with ursodeoxycholic acid (UDCA). Methods: After a pretreatment with TUDCA or UDCA, human gastric epithelial MKN-45 cells were stimulated with tumor necrosis factor (TNF)-alpha to activate NF-kappa B signaling. A real-time PCR (RT-PCR) for human interleukin (IL)-1 mRNA was performed. An electrophoretic mobility shift assay (EMSA) and immunoblot analyses were carried out. In murine models, after a pretreatment with TUDCA or UDCA, ethanol and indomethacin were administered via oral gavage. Macroscopic and microscopic assessments were performed to evaluate the preventive effects of TUDCA and UDCA on murine gastritis. Results: A pretreatment with TUDCA downregulated the IL-1 alpha mRNA levels in MKN-45 cells stimulated with TNF-alpha, as assessed by RT-PCR. As determined using EMSA, a pretreatment with TUDCA reduced the TNF-alpha-induced NF-kappa B DNA binding activity. A pretreatment with TUDCA inhibited I kappa B alpha phosphorylation induced by TNF-alpha, as assessed by immunoblot analysis. TUDCA attenuated the ethanol-induced and NSAID-induced gastritis in murine models, as determined macroscopically and microscopically. Conclusions: TUDCA inhibited NF-kappa B signaling in gastric epithelial cells and ameliorated ethanol-and NSAID-induced gastritis in murine models. These results support the potential of TUDCA for the prevention of gastritis in humans.
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