Attenuation of the ethanol-induced hepatic redox change after chronic alcohol consumption in baboons: Metabolic consequences in vivo and in vitro

Authors

  • Mikko P. Salaspuro,

    1. The Alcohol Research and Treatment Center and the Laboratory of Liver Disease and Nutrition, Veterans Administration Medical Center, Bronx, New York 10468
    2. Mount Sinai School of Medicine of the City University of New York, New York 10029
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  • Spencer Shaw,

    1. The Alcohol Research and Treatment Center and the Laboratory of Liver Disease and Nutrition, Veterans Administration Medical Center, Bronx, New York 10468
    2. Mount Sinai School of Medicine of the City University of New York, New York 10029
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  • Elizabeth Jayatilleke,

    1. The Alcohol Research and Treatment Center and the Laboratory of Liver Disease and Nutrition, Veterans Administration Medical Center, Bronx, New York 10468
    2. Mount Sinai School of Medicine of the City University of New York, New York 10029
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  • William A. Ross,

    1. The Alcohol Research and Treatment Center and the Laboratory of Liver Disease and Nutrition, Veterans Administration Medical Center, Bronx, New York 10468
    2. Mount Sinai School of Medicine of the City University of New York, New York 10029
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  • Dr. Charles S. Lieber

    Corresponding author
    1. The Alcohol Research and Treatment Center and the Laboratory of Liver Disease and Nutrition, Veterans Administration Medical Center, Bronx, New York 10468
    2. Mount Sinai School of Medicine of the City University of New York, New York 10029
    • Alcohol Research and Treatment Center, Veterans Administration Medical Center, Bronx, New York 10468
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Abstract

Acute ethanol administration results in increased hepatic NADH/NAD+ ratio and inhibition of galactose elimination, tricarboxylic acid cycle activity, and fatty acid oxidation. To determine how this redox change is affected by chronic alcohol consumption and to assess the resulting metabolic consequences, we studied baboons which were fed alcohol as 50% of their total calories. Redox changes were evaluated through measurement of galactose elimination in vivo and lactate/pyruvate ratios in liver slices in vitro. The metabolic consequences of these changes were assessed through measurement of CO2 production and fatty acid oxidation in liver slices and hepatic lipid accumulation. Chronic alcohol feeding resulted in attenuation of inhibition of galactose elimination, increase in the lactate/pyruvate ratio, and decrease in fatty acid oxidation which were caused by acute ethanol administration. These metabolic adaptations were associated with reduced accumulation of hepatic fat.

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