title: Therapeutic effects of ezetimibe for non-alcoholic steatohepatitis in fatty liver shionogi-ob/ob mice.
abstract: OBJECTIVE
  An effective therapy for non-alcoholic steatohepatitis has yet to be defined. This study examined the therapeutic effects of ezetimibe, a lipid-lowering medication, on steatosis and hepatic fibrosis in fatty liver Shionogi ob/ob (FLS-ob) mice.
  
  
  METHODS
  Low-dose (0.2 mg/kg body weight) and high-dose (1.0 mg/kg body weight) of ezetimibe were administered to FLS-ob mice orally for 12 weeks.
  
  
  RESULTS
  Administration of ezetimibe significantly and dose-dependently decreased liver cholesterol content. The area of hepatic fibrosis and hepatic hydroxyproline content in the low- and high-dose groups were significantly decreased compared with controls. Areas of α-smooth muscle actin positivity and F4/80 positivity were significantly decreased in a dose-dependent manner. Percentages of 8-hydroxy-2-deoxyguanosine-positive cells in low- and high-dose groups were significantly decreased compared with those in controls, and 8-hydroxy-2-deoxyguanosine DNA content and thiobarbituric acid reactive substances in the high-dose group was also significantly decreased compared to controls. Gene expression levels of procollagen I and transforming growth factor β1 mRNA levels were lower in the low- and high-dose groups than in controls. Tumor necrosis factor-α and sterol regulatory element-binding protein 1c mRNA levels were also lower in the low- and high-dose groups than in controls.
  
  
  CONCLUSIONS
  Ezetimibe attenuated steatosis and liver fibrosis by reducing oxidative stress and lipid peroxidation and suppressing activated hepatic stellate cells and Kupffer cells.
authors.affiliation: Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Matono
authors.forename: Masahiko
authors.initials: M
authors.lastname: Koda
authors.forename: Shiho
authors.initials: S
authors.lastname: Tokunaga
authors.forename: Jun
authors.initials: J
authors.lastname: Kato
authors.forename: Takaaki
authors.initials: T
authors.lastname: Sugihara
authors.forename: Masaru
authors.initials: M
authors.lastname: Ueki
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Murawaki