bicyclol and Liver-Diseases--Alcoholic

Topics: Biphenyl Compounds; Female; Humans; Liver Diseases, Alcoholic; Male; Middle Aged; Phosphatidylcholines

Oxidative stress, cytokine over expression and Kupffer cell activation are well-documented pathological factors in the development of alcoholic liver disease. Bicyclol is a novel synthetic anti-hepatitis drug with anti-oxidative and anti-inflammatory property. The present study was to investigate the effect of bicyclol on acute alcohol-induced liver injury and related mechanisms in mice. Bicyclol (200, 300 mg/kg) was given to mice by gavage for three times. Alcohol (6 g/kg) was administered orally 1 h after the last dose of bicyclol. All animals were sacrificed at different time points after alcohol administration. Liver injury was evaluated by biochemical and histopathological examination. Lipid peroxidation and the activity of antioxidants were measured by spectrophotometric method. Expression of cytokines and CD14 were determined by enzyme-linked immunosorbent assay, reverse transcriptional-polymerase chain reaction and immunohistochemical staining. As a result, bicyclol pretreatment significantly protected against acute alcohol-induced liver injury as evidenced by the decrease of elevated serum alanine aminotransferase and hepatic triglyceride, and the attenuation of histopathological changes in mice. In addition, bicyclol remarkably alleviated the formation of thiobarbituric acid-reactive substance and restored impaired antioxidants, including glutathione, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. Over-expression of cytokines, such as tumor necrosis factor alpha and interleukin 1beta, elevated plasma endotoxin level, and up-regulation of CD14 were also suppressed by bicyclol in alcohol-intoxicated mice. The protective effect of bicyclol on alcohol-induced hepatotoxicity was mainly due to its ability to attenuate oxidative stress, suppress the cytokine expression at both protein and gene level, and inhibit the activation of Kupffer cells by decreasing plasma endotoxin level and CD14 expression.

Topics: Acute Disease; Animals; Antioxidants; Aspartate Aminotransferases; Biphenyl Compounds; Cytokinins; Endotoxins; Glutathione; Immunohistochemistry; Indicators and Reagents; Interleukin-1beta; Kupffer Cells; Lipid Peroxidation; Lipopolysaccharide Receptors; Liver; Liver Diseases, Alcoholic; Male; Mice; Mice, Inbred ICR; Oxidative Stress; Reverse Transcriptase Polymerase Chain Reaction; Subcellular Fractions; Triglycerides; Tumor Necrosis Factor-alpha

To study the protective effect of bicyclol on alcohol-induced liver injury in mice.. 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.. 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).. Bicyclol protects mice against alcohol-induced hepatotoxicity by reduction of hepatic steatosis and cellular damage, acceleration of alcohol and aldehyde elimination and anti-peroxidation.

Topics: Alanine Transaminase; Aldehyde Dehydrogenase; Animals; Biphenyl Compounds; Cholesterol; Dimethylnitrosamine; Ethanol; Glutathione; Glutathione Reductase; Glutathione Transferase; Lipoproteins, HDL; Lipoproteins, LDL; Liver; Liver Diseases, Alcoholic; Male; Mice; Mice, Inbred Strains; Oxidoreductases, N-Demethylating; Random Allocation; Triglycerides