allopurinol and Liver-Cirrhosis--Alcoholic

Xanthine oxidoreductase (XOR) is a widely distributed enzyme, involved in the metabolism of purines, which generates superoxide and is thought to be involved in free radical-generated tissue injury. It is present at high concentrations in the liver, from where it may be released during liver injury into the circulation, binding to vascular endothelium and causing vascular dysfunction. The cellular localization of the enzyme, essential to understanding its function, is, however, still debated. The present study has used a highly specific mouse monoclonal antibody to define the cellular distribution of XOR in normal and cirrhotic human liver. As shown previously, XOR is present in hepatocytes. However, the novel finding of this study is that XOR is present in bile duct epithelial cells, where it is concentrated toward the luminal surface. Moreover, in liver disease, proliferating bile ducts are also strongly positive for XOR. These findings suggest that the enzyme is secreted into bile, and this was confirmed by analysis of human and rat bile. Xanthine oxidase activity was 10 to 20-fold higher in liver tissue obtained from patients with liver disease, than in healthy liver. We conclude that XOR is expressed primarily in hepatocytes, but is also present in bile duct epithelial cells and is secreted into bile. Its role in bile is unknown but it may be involved in innate immunity of the bowel muscosa.

Topics: Animals; Antibodies, Monoclonal; Bile; Bile Ducts; Blotting, Western; Cell Polarity; Cholangitis, Sclerosing; Electrophoresis, Polyacrylamide Gel; Epithelial Cells; Hepatitis C; Hepatocytes; Humans; Hyperoxaluria, Primary; Immunoenzyme Techniques; Liver Cirrhosis; Liver Cirrhosis, Alcoholic; Liver Cirrhosis, Biliary; Liver Diseases; Liver Diseases, Alcoholic; Mice; Mice, Inbred BALB C; Microscopy, Confocal; Rats; Rats, Sprague-Dawley; Xanthine Oxidase

A fatty liver resulting from alcohol intake is often unattractive for grafting. In this study, we investigated the impairment of hepatocytes and sinusoidal endothelial cells (SECs) during cold preservation of alcohol-induced fatty liver and examined the efficacy of human recombinant hepatocyte growth factor (hrHGF). Rats were fed an alcohol diet. We performed histological examinations of the hepatocytes and observed the ultrastructural alteration of the SECs. Additionally, we measured hepatic transaminase and peroxidative lipids for hepatocellular injury and the hyaluronic acid uptake rate (HUR) to determine SEC injury. We added hrHGF to University of Wisconsin (UW) solution to assess the protective effect of the agent. Numerous fatty deposits were observed in ethanol-induced fatty livers. These grew with the duration of cold storage. Hepatic transaminases of the effluents increased during cold preservation in the livers of alcohol-treated rats. Additionally, peroxidative lipids in the effluents increased during cold preservation in the livers of alcohol-treated rats, whereas they were undetectable in non-alcohol-treated rat livers. The sinusoidal endothelium had severely deteriorated in the livers of alcohol-treated rats. Further, the HUR decreased with ethanol treatment and/or cold preservation. The addition of hrHGF suppressed the increase of hepatic transaminase in the effluent of cold-preserved alcohol-treated livers. Peroxidative lipids in the same effluents were undetectable. In fatty livers, both hepatocytes and SECs received severe damage during cold preservation. Furthermore, we demonstrated that hepatocellular injury was significantly inhibited by hrHGF.

Topics: Adenosine; Allopurinol; Animals; Cold Temperature; Endothelium; Glutathione; Hepatocyte Growth Factor; Hepatocytes; Humans; Insulin; Liver Cirrhosis, Alcoholic; Male; Microscopy, Electron, Scanning; Organ Preservation Solutions; Raffinose; Rats; Rats, Wistar; Recombinant Proteins; Tissue Preservation

The effects of lentinan on enzyme induced lipid peroxidation, xanthine-xanthine oxidase-induced cytochrome c reduction, and on the superoxide-dismutase (SOD) enzyme activity and expression of human lymphocytes and erythrtocytes were studied. Lentinan in low concentration decreased SOD activity of lymphocytes and erythrocytes from healthy subjects. In higher concentration (10 micrograms/ml) lentinan increased the pathologically low SOD activity of erythrocytes and lymphocytes of patients with cirrhosis of the liver. No significant antioxidant (free radical scavenger) effect has been observed in NADPH-induced and Fe3+-stimulated lipid peroxidation and in xanthine-xanthine oxidase system.

Topics: Animals; Cytochrome c Group; Erythrocytes; Humans; In Vitro Techniques; Lentinan; Lipid Peroxidation; Liver Cirrhosis, Alcoholic; Lymphocytes; Male; Mice; Oxidation-Reduction; Polysaccharides; Rats; Rats, Inbred Strains; Superoxide Dismutase; Xanthine; Xanthine Oxidase; Xanthines

Topics: Acetaldehyde; Humans; Lipid Metabolism; Liver; Liver Cirrhosis, Alcoholic; Liver Diseases, Alcoholic; Models, Chemical; Oxidation-Reduction; Oxygen; Superoxides; Xanthine Oxidase