D-penicillamine prevents the development of hepatitis in long-evans cinnamon rats with abnormal copper metabolism

Authors

  • Yuji Togashi B. Pharm.,

    Corresponding author
    1. Laboratory of Pathology, Cancer Institute, Hokkaido University School of Medicine, Sapporo 060
    2. Research and Development Department for Medical Products, Tsumura Company, Tokyo 102, Japan
    • Laboratory of Pathology, Cancer Institute, Hokkaido University School of Medicine, Kita 15, Nishi 7, Sapporo 060, Japan
    Search for more papers by this author
  • Yu Li,

    1. Laboratory of Pathology, Cancer Institute, Hokkaido University School of Medicine, Sapporo 060
    2. First Department of Surgery, Hokkaido University School of Medicine, Sapporo 060
    Search for more papers by this author
  • Jong-Hon Kang,

    1. Laboratory of Pathology, Cancer Institute, Hokkaido University School of Medicine, Sapporo 060
    Search for more papers by this author
  • Noritoshi Takeichi,

    1. Laboratory of Pathology, Cancer Institute, Hokkaido University School of Medicine, Sapporo 060
    Search for more papers by this author
  • Yasunori Fujioka,

    1. Second Department of Pathology, Hokkaido University School of Medicine, Sapporo 060
    Search for more papers by this author
  • Kazuo Nagashima,

    1. Second Department of Pathology, Hokkaido University School of Medicine, Sapporo 060
    Search for more papers by this author
  • Hiroshi Kobayashi

    1. Laboratory of Pathology, Cancer Institute, Hokkaido University School of Medicine, Sapporo 060
    Search for more papers by this author

Abstract

The Long-Evans Cinnamon rat is a mutant strain that contracts hereditary hepatitis and, eventually, spontaneous hepatocellular carcinoma. Because we found a corresponding gross copper accumulation in the liver of the rats, we examined whether the development of hepatitis in our rat system could be prevented by administration of D-penicillamine. D-Penicillamine is a copper-chelating agent and one of the drugs effective for human Wilson's disease, in which abnormal copper metabolism is also observed. The results show that D-penicillamine treatment inhibited the elevation of serum transaminases, suppressed abnormal histological changes in the liver and completely prevented the onset of hepatitis in the Long-Evans Cinnamon rats. We further found that the copper concentration in the liver and serum copper and ceruloplasmin levels were decreased, whereas the urinary copper level was increased in the D-penicillamine—treated Long-Evans Cinnamon rats. These findings demonstrate that the pathogenesis of hereditary hepatitis in Long-Evans Cinnamon rats is due to abnormal copper accumulation in the liver. (HEPATOLOGY 1992;15:82–87).

Ancillary