Mechanism of protective action of bicyclol against CCl-induced liver injury in mice. |
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Authors: | Geng Tao Liu Yan Li Huai Ling Wei Hui Zhang Ji Yan Xu Ling Hong Yu |
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Affiliation: | Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. liugt@imm.ac.cn |
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Abstract: | Bicyclol is a novel synthetic drug for the treatment of chronic viral hepatitis in China. This paper reports the protective action of bicyclol against experimental liver injury in mice and its mechanism of action. Oral administration of bicyclol markedly reduced the elevated serum transaminases (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) and the hepatic morphologic changes induced by CCl(4) in mice. Mechanistic studies demonstrated that bicyclol significantly inhibited CCl(4)-induced lipid peroxidation of liver microsomes and (14)CCl(4) covalent binding to microsomal lipids and proteins in vitro, and decreased the level of the trichloromethyl free radical (*CCl(3)) generated from CCl(4) metabolism by NADPH-reduced liver microsomes. On the other hand, bicyclol neither directly inhibited the activity of ALT or AST in vitro nor affected hepatic ALT protein content in mice. These results suggest that bicyclol has remarkable hepatoprotective effects and its mechanism of action may be related to a decrease in free radical-induced damage to hepatocytes. |
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Keywords: | bicyclol CCl4 free radical hepatoprotection liver injury |
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