The Effect of Chronic Ethanol Ingestion on Ethanol Metabolizing Enzymes in Isolated Periportal and Perivenous Rat Hepatocytes

Authors

  • Hannu Väänänen,

    Corresponding author
    1. Research Laboratories of the Finnish State Alcohol Company, Alko Ltd., and Division of Gastroenterology, University Central Hospital of Helsinki, Helsinki, Finland
    • Hannu Väänänen, Research Laboratories of the Finnish State Alcohol Company, Alko Ltd., P.O. Box 350, SF-00101 Helsinki 10, Finland.
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  • Mikko Salaspuro,

    1. Research Laboratories of the Finnish State Alcohol Company, Alko Ltd., and Division of Gastroenterology, University Central Hospital of Helsinki, Helsinki, Finland
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  • Kai Lindros

    1. Research Laboratories of the Finnish State Alcohol Company, Alko Ltd., and Division of Gastroenterology, University Central Hospital of Helsinki, Helsinki, Finland
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  • A portion of this work was presented at the Fourteenth Annual Nordic Meeting on Biological Alcohol Research, Rungstedgaard, Denmark [Acta Pharmacol. Toxicol. 1983; 53(Suppl. II):A26, Abstract].

Abstract

Periportal (pp) and perivenous (pv) hepatocyte populations were separated using a two-diree-tional closed perfusion technique with selective addition of collagenase either to direct or retrograde perfusions (Vaananen, H. et al., Liver 1983; 3:131). The activity of GPT in hepatocytes from the pp-area was 1.9 times higher than in cells from the pv-area (p < 0.01). The distribution of glutamate dehydrogenase and pyruvate kinase activities was reversed; pp/pv ratios of 0.7 and 0.5, respectively, were observed (p < 0.001, p < 0.05). Chronic ethanol consumption for 12 weeks (mean daily ethanol intake 11.4 gm per body weight corresponding to 29% of total energy intake) did not cause histological changes but decreased GPT activity, increased glutamate dehydrogenase and pyruvate kinase activities and did not alter their pp/pv distribution. Alcohol dehydrogenase and aldehyde dehydrogenase activities were evenly distributed in pp- and pv-hepatocytes. Chronic ethanol treatment slightly decreased alcohol dehydrogenase activity (p < 0.05) and increased the activity of low Km aldehyde dehydrogenase (p < 0.001, p < 0.05). The specific activity of NADPH-dependent microsomal ethanol oxidation was 50% higher in pv-hepatocytes (p < 0.05). Chronic ethanol treatment did not increase the specific activity of microsomal ethanol oxidation but reduced the pp-pv activity difference.

The results indicate that the enzymatic capacity to oxidize ethanol is evenly distributed in the acinus and that, after long-term moderate ethanol treatment, despite lack of parenchymal lesions, changes in the activity of enzymes involved in ethanol metabolism are observed. These changes occur to the same extent in different acinar sites.

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