Alcohol-induced liver injury. The role of oxygen.
Alcoholism is a major health problem, and one of its primary manifestations is alcoholic liver disease. The mechanisms responsible for the various forms of alcoholic liver disease--fatty liver, alcoholic hepatitis, and cirrhosis--are at present poorly understood. Knowledge of these mechanisms is needed to provide a sound framework for the therapy and prevention of liver disease due to alcohol and for the identification of those individuals most susceptible to develop liver disease from alcohol abuse. These experiments were designed specifically to evaluate the postulate that ethanol-induced pericentral liver damage results from an accentuated gradient of decreasing oxygen tension leading to pericentral hypoxia. Microlight guides were used to detect NADH fluorescence, and miniature oxygen electrodes were employed to measure oxygen tensions from periportal and pericentral regions of the liver lobule from the perfused rat liver. With both techniques, ethanol treatment increased the hepatic oxygen gradient. This increase was blocked by the antithyroid drug propylthiouracil. Thus, these experiments provide evidence in support of the hypothesis that pericentral hypoxia is involved in the mechanism of ethanol-induced liver injury. Furthermore, low-flow hypoxia was shown to cause blebs in the pericentral region of the liver lobule in as little as 15 min. This surface blebbing could represent the mechanism for the well-known release of enzymes by impaired hepatic tissues.
D000079:Acetaldehyde / Q000378:metabolism; D000426:Alcohol Dehydrogenase; D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000437:Alcoholism / Q000201:enzymology; D000818:Animals; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008102:Liver Circulation / Q000187:drug effects; D008108:Liver Diseases, Alcoholic / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control; D008855:Microscopy, Electron, Scanning; D009243:NAD / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D011441:Propylthiouracil / Q000627:therapeutic use; D051381:Rats
D009243:NAD; D011441:Propylthiouracil; D000429:Alcohol Oxidoreductases; D000426:Alcohol Dehydrogenase; D007770:L-Lactate Dehydrogenase; D000079:Acetaldehyde