Alcohol Induced Susceptibility to Hypoxic Liver Damage: Possible Role in the Pathogenesis of Alcoholic Liver Disease?

  • Y. Israel
  • H. Orrego
  • J. M. Khanna
  • D. J. Stewart
  • M. J. Phillips
  • H. Kalant


Previous studies in our laboratory (1–3), have indicated that the major rate limiting factor in ethanol metabolism in the intact liver cell is the rate of mitochondrial reoxidation to NAD+ of NADH produced in the oxidation of ethanol. This has now been confirmed in several laboratories (4–8). In this process oxygen is utilized and water is formed. The capacity of mitochondria to oxidize reducing equivalents is related to the relative availability of phosphate acceptor (ADP), or more generally to the phosphorylation potential (ATP/ADP × Pi) (9–12). Mitochondrial uncouplers such as dinitrophenol (DNP), carbonyl cyanide p-trifluoromethoxyphenyl-hydrazone (FCCP) and arsenate allow the mitochondria to oxidize reducing equivalents independently of phosphate acceptor availability and thus they increase the rate of oxygen consumption (13). Accordingly, the rate of ethanol metabolism has been shown to be increased by uncoupling agents both in vivo (2,4) and in vitro in liver slices (1, 14), perfused liver (3,5) and isolated hepatocytes (8). Figure 1 shows the effect of DNP on the rate of ethanol metabolism by perfused rat liver.


Basal Metabolic Rate Alcoholic Liver Disease Chronic Ethanol Alcoholic Hepatitis Ethanol Metabolism 
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Copyright information

© Plenum Press, New York 1977

Authors and Affiliations

  • Y. Israel
    • 1
    • 2
  • H. Orrego
    • 1
    • 2
  • J. M. Khanna
    • 1
    • 2
  • D. J. Stewart
    • 1
    • 2
  • M. J. Phillips
    • 1
    • 2
  • H. Kalant
    • 1
    • 2
  1. 1.Departments of Pharmacology, Physiology and PathologyUniversity of TorontoCanada
  2. 2.Addiction Research FoundationCanada

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