Hepatology research : the official journal of the Japan Society of Hepatology · 2011
Therapeutic effects of ezetimibe for non-alcoholic steatohepatitis in fatty liver shionogi-ob/ob mice.
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Matono Tomomitsu, Koda Masahiko, Tokunaga Shiho, Kato Jun, Sugihara Takaaki, Ueki Masaru, Murawaki Yoshikazu
Аннотация
AIM: 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.
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.