• Ching-Chih Chang, Hui-Chun Huang, Shao-Jung Hsu, Chon-Kit Pun, Chiao-Lin Chuang, Ming-Chih Hou, and Fa-Yauh Lee.
• Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC.
• J Chin Med Assoc. 2024 May 1; 87 (5): 463470463-470.

BackgroundIn liver cirrhosis, chronic inflammation is associated with an increase in oxidative stress, and subsequently an increase in the concentration of oxidized low-density lipoprotein (ox-LDL). Ezetimibe is a lipid-lowering agent with anti-inflammation and anti-oxidative stress activities. This study aimed to investigate the effect of ezetimibe treatment on ox-LDL in cirrhotic rats.MethodsBiliary cirrhosis was induced in Sprague-Dawley rats with common bile duct ligation (BDL). Sham-operated rats served as surgical controls. Ezetimibe (10 mg/kg/d) or vehicle was administered in the sham-operated or BDL rats for 4 weeks, after which hemodynamic parameters, biochemistry data, and oxidative stress were evaluated. Plasma and intrahepatic ox-LDL levels were also examined, and hepatic proteins were analyzed to explore the mechanism of ezetimibe treatment.ResultsThe BDL rats had typical features of cirrhosis including jaundice, impaired liver function, hyperlipidemia, and elevated ox-LDL levels compared to the sham-operated rats. Ezetimibe treatment did not affect hemodynamics, liver biochemistry, or plasma lipid levels. However, it significantly reduced oxidative stress, plasma levels of ox-LDL, and tumor necrosis factor α. In addition, ezetimibe upregulated the hepatic protein expression of an ox-LDL scavenger (lectin-like ox-LDL rececptor-1), which resulted in reductions in intrahepatic ox-LDL and fat accumulation in the BDL rats. Nevertheless, ezetimibe treatment did not ameliorate hepatic inflammation or liver fibrosis.ConclusionEzetimibe reduced plasma and intrahepatic ox-LDL levels in the cirrhotic rats. Furthermore, it ameliorated intrahepatic fat accumulation and oxidative stress. However, ezetimibe did not alleviate hepatic fibrosis or inflammation in the biliary cirrhotic rats.Copyright © 2024, the Chinese Medical Association.

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