Molecular biological aspects of alcohol-induced liver disease.
Molecular biological investigations have become a predominant methodology applied to the study of alcohol-induced liver disease. The enzymatic pathways responsible for ethanol metabolism, and their genetic as well as environmental control, have become the focus of detailed investigation. More recently, the significance of cytokines in the pathogenesis of alcohol-induced liver disease has also become a major area of speculation. This review focuses on the advances made in studies of two important enzymes responsible for alcohol metabolism, alcohol dehydrogenase and aldehyde dehydrogenase, as well as the investigation of the proinflammatory and profibrogenic cytokines involved in the process of hepatic fibrogenesis. The quality and quantity of new discoveries made in the field of alcohol-induced liver disease is impressive, especially when one realizes that molecular biological approaches have been employed in this area for only 15 years. However, in most cases the studies have been predominantly descriptive, with little direct relevance to the therapeutics of alcoholism and alcohol-induced organ injury. Because the groundwork has been laid, one hopes that the next 15 years will rectify this failure.
Arnon
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R
Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Esposti
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SD
Zern
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MA
D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000818:Animals; D000431:Ethanol / Q000493:pharmacokinetics; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008104:Liver Cirrhosis, Alcoholic / Q000201:enzymology / Q000235:genetics*; D011110:Polymorphism, Genetic
D000431:Ethanol; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase