title: Pravastatin activates PPARalpha/PPARgamma expression in the liver and gallbladder epithelium of hamsters.
abstract: BACKGROUND
  Our earlier study with cultured gallbladder epithelial cells demonstrated that statins (HMG-CoA reductase inhibitors) activate the expression of PPARalpha and PPARgamma, consequently blocking the production of pro-inflmmatory cytokines. The present study used hamsters to investigate the effects of pavastatin on PPARalpha/PPARgamma 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 PPARalpha and PPARgamma 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 PPARalpha and PPARgamma expression of gallbladder epithelial cells and hepatocytes, and particularly the response of PPARgamma was much stronger than that of PPARalpha. Pravastatin suppressed the formation of cholesterol gallstones or crystals in the gallbladder.
  
  
  CONCLUSIONS
  Pravastatin is an effective medication to activate PPARs (especially PPARgamma) in the liver and the gallbladder epithelium of hamsters, and contributes to the prevention of gallstone formation.
authors: Division of Gastroenterology, Department of Internal Medicine, Kyung Hee University College of Medicine, Seoul, Republic of Korea.
authors: Seok Ho
authors: SH
authors: Dong
authors: Jin
authors: J
authors: Lee
authors: Dong Hee
authors: DH
authors: Koh
authors: Min Ho
authors: MH
authors: Choi
authors: Hyun Joo
authors: HJ
authors: Jang
authors: Sea Hyub
authors: SH
authors: Kae
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D006224:Cricetinae; D005704:Gallbladder / Q000737:chemistry / Q000187:drug effects*; D042882:Gallstones / Q000517:prevention & control*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007150:Immunohistochemistry; D008099:Liver / Q000737:chemistry / Q000187:drug effects*; D008297:Male; D008647:Mesocricetus; D047493:PPAR alpha / Q000032:analysis*; D047495:PPAR gamma / Q000032:analysis*; D017035:Pravastatin / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D047493:PPAR alpha; D047495:PPAR gamma; D002784:Cholesterol; D017035:Pravastatin