P006. Tauro-ursodeoxycholic acid ameliorates experimental colitis in mice
Y.H. Kim1, S.-J. Koh1, W.J. Choi1, S.H. Kim1, J.W. Kim1, B.G. Kim1, K.L. Lee1, 1Seoul National University Boramae Hospital, Internal Medicine, Seoul, South Korea
Tauro-ursodeoxycholic acid (TUDCA) is an endogenous bile acid synthesized in the liver conjugation pathway of ursodeoxycholic acid. TUDCA exhibited anti-inflammatory effects on intestinal epithelial cells; however, little information is available on intestinal inflammation in vivo study.
HCT 116 cells were pretreated with TUDCA and stimulated with tumor necrosis factor-α (TNF-α). Interleukin-8 (IL-8) expression was determined by real-time RT-PCR. IκB degradation was evaluated by western blotting. Seven-week old specific pathogen-free C57BL/6 mice were divided into four groups. Five mice in each group were randomly assigned after they were weighted. Dextran sulfate sodium (DSS) was dissolved in drinking water and administered for 5 days. TUDCA (50 mg/kg and 250 mg/kg per day) was suspended in phosphate buffered solution (PBS) and treated once daily by oral gavage, beginning 2 days before DSS administration. The mice were euthanized on day 7. The severity of colitis was assessed by body weight change, disease activity index (DAI), colon length, and histopathology.
TUDCA significantly inhibited IL-8 expression in HCT 116 cells stimulated with TNF-α. Pretreatment with TUDCA attenuated I κ κB α degradation induced by TNF-α. In an acute murine colitis model, significant changes of body weight and DAI were observed in the vehicle-treated mice. However, the administration of TUDCA significantly ameliorated acute colitis as assessed by body weight change and DAI. The administration of TUDCA also attenuated DSS-induced colon shortening compared to vehicle treatment. In the histopathologic evaluation, DSS administration induced severe colitis including complete destruction of epithelial structure and severe inflammatory cell infiltraton. However, mice treated with TUDCA showed significant improvement such as maintained crypt architecture and scanty infiltration of inflammatory cells.
Our preliminary results showed that TUDCA had anti-inflammatory effect both in vivo and in vitro; thus, TUDCA is a potential therapeutic agent for the treatment of inflammatory bowel disease.