Decreased expression of liver glutathione peroxidase in Long-Evans cinnamon mutant rats predisposed to hepatitis and hepatoma

Authors

  • Hiroshi Suemizu,

    1. Department of Molecular Life Science (Cell Biology), Tokai University School of Medicine, Isehara 259-11
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  • Shinichi Yoshimura,

    1. Department of Molecular Life Science (Cell Biology), Tokai University School of Medicine, Isehara 259-11
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  • Noritoshi Takeichi,

    1. Laboratory of Cell Biology, Cancer Institute, Hokkaido University School of Medicine, Sapporo 060, Japan
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  • Tetsuya Moriuchi M.D.

    Corresponding author
    1. Department of Molecular Life Science (Cell Biology), Tokai University School of Medicine, Isehara 259-11
    • Department of Molecular Life Science (Cell Biology), Tokai University School of Medicine, Isehara 259-11, Japan
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Abstract

The Long-Evans Cinnamon rat is a mutant strain that contracts hereditary hepatitis and, eventually, spontaneous hepatoma. Recently, abnormal copper accumulations in Long-Evans Cinnamon rat livers were shown to be genetically linked to the development of hepatitis. Because reduced glutathione and glutathione-related enzymes are known to play important roles in cellular resistance to transition metal toxicity, we determined the levels of reduced glutathione and glutathione-related enzymes in seven different tissues of Long-Evans Cinnamon and control Long-Evans Agouti rats. Of the enzymes examined, only hepatic glutathione peroxidase was markedly decreased in Long-Evans Cinnamon rats. Glutathione peroxidase content in the liver of Long-Evans Cinnamon rats was 39%, 53% and 58% of the control values at 9 (normal stage), 19 (acute hepatitis stage) and 27 (chronic hepatitis stage) wk of age, respectively. Northern-blot analysis revealed that messenger RNA levels of glutathione peroxidase in the livers of Long-Evans Cinnamon rats were about 40% of the control levels. The activity of glutathione S-transferase was slightly decreased in the livers of Long-Evans Cinnamon rats. These data suggest that the liver of the Long-Evans Cinnamon rat is poorly protected against active oxygen species, the production of which is enhanced in the presence of excess copper. Glutathione-reductase activity in the livers of Long-Evans Cinnamon rats increased to 166% and 148% of the control levels at 19 and 27 wk of age, respectively. No significant changes were observed in the activity of γ-glutamylcysteine synthetase or in the content of total reduced glutathione in the liver of the Long-Evans Cinnamon rat. The changes in activity of glutathione peroxidase and glutathione reductase in the Long-Evans Cinnamon rat livers resembled those observed during chemical hepatocarcinogenesis. (Hepatology 1994;19:694–700).

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