Mechanism of protective action of bicyclol against CCl-induced liver injury in mice.
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.
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. liugt@imm.ac.cn
Geng Tao
GT
Liu
Yan
Y
Li
Huai Ling
HL
Wei
Hui
H
Zhang
Ji Yan
JY
Xu
Ling Hong
LH
Yu
D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D001713:Biphenyl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D002251:Carbon Tetrachloride / Q000031:analogs & derivatives / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D006520:Hepatitis, Animal / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D050356:Lipid Metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000998:Antiviral Agents; D001713:Biphenyl Compounds; D020011:Protective Agents; D011506:Proteins; C025280:trichloromethyl free radical; C477843:bicyclol; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase