[Protective effects of bicyclol on alcohol-induced liver damage in mice].
OBJECTIVE
To study the protective effect of bicyclol on alcohol-induced liver injury in mice.


METHODS
Sixty male mice were randomly divided into 6 groups. Ten mice were fed with Lieber-Decarli liquid diet without alcohol and used as normal controls. Fifty mice were fed with Lieber-Decarli liquid diet containing 5% alcohol for four weeks so as to establish a model of alcohol-induced liver damage. Ten mice fed with Lieber-Decarli liquid diet containing 5% alcohol for four weeks were used as model group. Bicyclol in a dose of either 200 or 300 .kg(-1).d(-1) was given orally simultaneously with alcohol intake as prevention groups (10 mice in each group), and bicyclol in a dose of either 200 or 300 .kg(-1).d(-1) was given orally 2 weeks after the beginning of alcohol intake as treatment groups (10 mice in each group). Twenty-four hours after the last dose of bicyclol the mice were decapitated and then their blood samples and livers were taken. The serum alanine aminotransferase (ALT), cholesterol (CHOL), and high-density lipoprotein/low-density lipoprotein (HDL/LDL), and liver triglyceride (TG), N-nitrosodimethylamine demethylase (NDMA-DM), glutathione (GSH), glutathione S-transferase (GST), glutathione reductase (GR), and aldehyde dehydrogenase (ALDH) were determined by biochemical assays. The extent of liver damage was evaluated by histological examination.


RESULTS
Four weeks after alcohol intake the serum ALT and TG were 1.9 and 2.7 times those of the normal control group. The levels of liver TG of the bicyclol 200 kg(-1).d(-1) and 300 kg(-1).d(-1) treatment groups were significantly lower than that of the model group by 28% and 32% respectively (both P < 0.05). The levels of liver TG of the bicyclol 200 kg(-1).d(-1) and 300 kg(-1).d(-1) prevention groups were significantly lower than that of the model group by 32%, and 47% respectively (both P < 0.01). Pathological changes including steatosis and hepatocyte ballooning degeneration were found in the livers of the model group. The levels of liver GSH, GST, and GR in the model group decreased by 37%, 22%, and 19% in comparison with the normal control group. The levels of liver GSH and GST of the bicyclol prevention groups were normal, and the liver GR level was 1.2 times that of the normal control group. The liver NDMA-DM activity of the model group was 1.9 times that of the normal control group and was normal in the bicyclol prevention and treatment groups. The liver cytoplasmic ALDH level was 30% lower in the model group than in the normal control group (P < 0.05), and was 2.9 times in the bicyclol groups (P < 0.01). The serum cholesterol levels of the bicyclol groups were all significantly lower than that of the model group (all P < 0.01). The serum levels of HDL of the bicyclol prevention groups and treatment were all significantly lower than that in the model group (P < 0.01 or P < 0.05).


CONCLUSIONS
Bicyclol protects mice against alcohol-induced hepatotoxicity by reduction of hepatic steatosis and cellular damage, acceleration of alcohol and aldehyde elimination and anti-peroxidation.
Mo
Cheng-lin
CL
Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China.
Li
Ye
Y
Li
Yan
Y
D000410:Alanine Transaminase / Q000097:blood; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood; D004128:Dimethylnitrosamine / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D011897:Random Allocation; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
D001713:Biphenyl Compounds; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D014280:Triglycerides; D000431:Ethanol; C477843:bicyclol; D002784:Cholesterol; D000444:Aldehyde Dehydrogenase; D010089:Oxidoreductases, N-Demethylating; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D000410:Alanine Transaminase; D005978:Glutathione; D004128:Dimethylnitrosamine