BACKGROUND: Our earlier study with cultured gallbladder epithelial cells demonstrated that statins (HMG-CoA reductase inhibitors) activate the expression of PPARα and PPARγ, consequently blocking the production of pro-inflmmatory cytokines. The present study used hamsters to investigate the effects of pavastatin on PPARα/PPARγ expression in the liver and gallbladder epithelium, and to determine whether pravastatin suppresses cholesterol crystal formation in the gallbladder.
METHODS: A total of 40 Golden Syrian male hamsters (4 weeks old) were randomly assigned to four groups (basal diet control; basal diet+pavastatin; high cholesterol diet; high cholesterol diet+pravastatin). All hamsters were 11 weeks old at the end of the experiment. The liver, gallbladder and bile were harvested. Immunohistochemical staining and Western blotting for PPARα and PPARγ were performed in the liver and gallbladder. A drop of fresh bile was examined for cholesterol crystals under a microscope.
RESULTS: In the gallbladder and liver of the hamsters, pravastatin activated the PPARα and PPARγ expression of gallbladder epithelial cells and hepatocytes, and particularly the response of PPARγ was much stronger than that of PPARα. Pravastatin suppressed the formation of cholesterol gallstones or crystals in the gallbladder.
CONCLUSION: Pravastatin is an effective medication to activate PPARs (especially PPARγ) in the liver and the gallbladder epithelium of hamsters, and contributes to the prevention of gallstone formation.