all of the mice fed with CDHF diet for 8 weeks. Serum biochemical indicators
of hepatic function and liver histological changes as well as gene expression of estrogen receptor (ER)-α, which is the predominant ER in the liver were evaluated. Results: Liver weight/ body weight ratios of the OVX group were significantly lower than those of sham group. Serum alanine aminotransferase (ALT) levels were significant decreased in the RLX group than those in the OVX group. The OVX group developed extensive steatosis with lobular inflammation and BAY 73-4506 molecular weight fibrosis. Scoring assessment of NAFLD/NASH severity was performed according to Kleiner scale known as NAFLD activity score (NAS). Although there was no statistically significant difference in histological steatosis score between these groups, raloxifene administration significantly decreased the lobular inflammatory scores than the OVX group, resulted in a significant lower NAS score. RLX group also showed a significant decrease of hepatic fibrosis staging compared with the OVX group. Furthermore, RLX group significantly increased the expression of hepatic
ER-a which was significantly decreased in OVX group than that in sham group. Conclusion: Raloxifene may have potential effect to ameliorate liver inflammation and fibrosis progression of NASH in ovariectomized mice. Angiogenesis inhibitor Disclosures: Hidemi Goto – Grant/Research Support: MSD, Roche, Bayer, Bristol-Myers, 上海皓元医药股份有限公司 Eisai, Ajinomoto, Otsuka, Astra, Tanabe The following people have nothing to disclose: Fangqiong Luo, Masatoshi
Ishi-gami, Yoji Ishizu, Teiji Kuzuya, Takashi Honda, Kazuhiko Hayashi Background: Emerging evidence has established the important role of the “gut-liver” axis in the development of alcoholic liver disease (ALD). Our recent work indicated that chronic alcohol induced perturbations in the gut microbiome and consequent decrease in short chain fatty acids, particularly butyrate, have a major impact on the development of intestinal barrier dysfunction and ALD. Butyrate has been shown to have beneficial gastrointestinal effects and to decrease obesity associated inflammation, hepatic steatosis and insulin resistance. The aim of this study was to investigate whether treatment with tributyrin (Tb; a butyrate prodrug) results in protection against ALD. Tb is a triglyceride that is rapidly absorbed and metabolized to butyrate. It has more favorable pharmacokinetics compared with butyrate with low toxicity. Methods: In the present study, we used a mouse model of ALD to examine the effects of Tb oral administration on ethanol-induced changes in intestinal permeability and hepatic steatosis, inflammation and injury. 8-10-week old C57BL/6 male mice were pair-fed the Lieb-er-DeCarli liquid diet containing alcohol (AF, n =8) or isoca-loric maltose dextrin (PF, n =8) for 4 weeks.