{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,6,23]],"date-time":"2024-06-23T05:11:33Z","timestamp":1719119493253},"reference-count":31,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2011,9,26]],"date-time":"2011-09-26T00:00:00Z","timestamp":1316995200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatology Research"],"published-print":{"date-parts":[[2011,12]]},"abstract":"<jats:p><jats:bold>Aim:\u2002<\/jats:bold> An effective therapy for non\u2010alcoholic steatohepatitis has yet to be defined. This study examined the therapeutic effects of ezetimibe, a lipid\u2010lowering medication, on steatosis and hepatic fibrosis in fatty liver Shionogi ob\/ob (FLS\u2010ob) mice.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> Low\u2010dose (0.2\u2003mg\/kg body weight) and high\u2010dose (1.0\u2003mg\/kg body weight) of ezetimibe were administered to FLS\u2010ob mice orally for 12\u2003weeks.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> Administration of ezetimibe significantly and dose\u2010dependently decreased liver cholesterol content. The area of hepatic fibrosis and hepatic hydroxyproline content in the low\u2010 and high\u2010dose groups were significantly decreased compared with controls. Areas of \u03b1\u2010smooth muscle actin positivity and F4\/80 positivity were significantly decreased in a dose\u2010dependent manner. Percentages of 8\u2010hydroxy\u20102\u2010deoxyguanosine\u2010positive cells in low\u2010 and high\u2010dose groups were significantly decreased compared with those in controls, and 8\u2010hydroxy\u20102\u2010deoxyguanosine DNA content and thiobarbituric acid reactive substances in the high\u2010dose group was also significantly decreased compared to controls. Gene expression levels of procollagen I and transforming growth factor \u03b21 mRNA levels were lower in the low\u2010 and high\u2010dose groups than in controls. Tumor necrosis factor\u2010\u03b1 and sterol regulatory element\u2010binding protein 1c mRNA levels were also lower in the low\u2010 and high\u2010dose groups than in controls.<\/jats:p><jats:p><jats:bold>Conclusions:\u2002<\/jats:bold> Ezetimibe attenuated steatosis and liver fibrosis by reducing oxidative stress and lipid peroxidation and suppressing activated hepatic stellate cells and Kupffer cells.<\/jats:p>","DOI":"10.1111\/j.1872-034x.2011.00888.x","type":"journal-article","created":{"date-parts":[[2011,9,28]],"date-time":"2011-09-28T00:28:58Z","timestamp":1317169738000},"page":"1240-1248","source":"Crossref","is-referenced-by-count":8,"title":["Therapeutic effects of ezetimibe for non\u2010alcoholic steatohepatitis in fatty liver shionogi\u2010ob\/ob 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