Abstract: Objective To determine the effects of probucol on serum parameters and liver histopathology in rats with
non-alcoholic steatohepatitis (NASH) and explore the mechanisms. Methods Forty male Sprague-Dawley rats were randomly
assigned into 4 equal groups, namely the normal control group (NC group) with a standard feeding, high-fat diet group (HD
group) fed with a high-fat diet, probucol (500 mg/kg daily) control group (NP group) fed with standard diet, and probucol
group fed with a high-fat diet (HP group). After 15 weeks of feeding, the rats were euthanized for histopathological inspection
of the liver with HE staining and detection of farnesoid X receptor (FXR), SHP and SREBP-1C expressions using
semi-quantitative RT-PCR and Western blotting. Results After the 15-week feeding, the rats in HP group had significantly
lower levels of serum ALT, AST, cholesterol, bile acid, and free fatty acid than those in HD group (P<0.01 or 0.05). Compared
with the normal control group, high-fat diet feeding resulted in significantly decreased mRNA and protein levels of FXR and
SHP (P<0.05) and significantly increased SREBP-1C level (P<0.05). These high-fat diet-induced gene expression changes were
reversed by probucol intervention (P<0.05). Conclusion Probucol treatment has beneficial effects on serum parameters, hepatic
steatosis, and lobular inflammation in high-fat diet-induced NASH possibly by up-regulating FXR expression.