Hepatotoxicity due to allyl alcohol in deermice depends on alcohol dehydrogenase

Authors

  • Steven A. Belinsky,

    1. Departments of Pharmacology, Pathology and Biochemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27514 and Department of Biology, University of South Carolina, Columbia, South Carolina 29208
    Current affiliation:
    1. National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709
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  • Blair U. Bradford,

    1. Departments of Pharmacology, Pathology and Biochemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27514 and Department of Biology, University of South Carolina, Columbia, South Carolina 29208
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  • Donald T. Forman,

    1. Departments of Pharmacology, Pathology and Biochemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27514 and Department of Biology, University of South Carolina, Columbia, South Carolina 29208
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  • Edward B. Glassman,

    1. Departments of Pharmacology, Pathology and Biochemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27514 and Department of Biology, University of South Carolina, Columbia, South Carolina 29208
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  • Michael R. Felder,

    1. Departments of Pharmacology, Pathology and Biochemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27514 and Department of Biology, University of South Carolina, Columbia, South Carolina 29208
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  • Ronald G. Thurman Ph.D.

    Corresponding author
    1. Departments of Pharmacology, Pathology and Biochemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27514 and Department of Biology, University of South Carolina, Columbia, South Carolina 29208
    • Department of Pharmacology 231H, 1124 Faculty Laboratory Office Building, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27514
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Abstract

The role of alcohol dehydrogenase in the hepatic necrosis due to allyl alcohol was studied in two strains of the deermouse, Peromyscus maniculatus. Mice of the alcohol dehydrogenase-negative (AdhN) strain which lack alcohol dehydrogenase activity were resistant to allyl alcohol toxicity. In contrast, dose-dependent necrosis of periportal regions of the liver and increases in plasma levels of lactate dehydrogenase, sorbitol dehydrogenase and SGOT were observed in plasma from alcohol dehydrogenase-positive deermice (AdhF) 24 hr following administration of allyl alcohol (21 to 84 mg per kg). Half-maximal damage to periportal areas was observed with about 52 mg per kg allyl alcohol. Thus, these data demonstrate that metabolism of allyl alcohol to acrolein by alcohol dehydrogenase is obligatory for the hepatotoxicity of allyl alcohol.

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