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D ‐penicillamine prevents the development of hepatitis in long‐evans cinnamon rats with abnormal copper metabolism
Author(s) -
Togashi Yuji,
Li Yu,
Kang JongHon,
Takeichi Noritoshi,
Fujioka Yasunori,
Nagashima Kazuo,
Kobayashi Hiroshi
Publication year - 1992
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840150116
Subject(s) - penicillamine , ceruloplasmin , medicine , endocrinology , hepatitis , wilson's disease , copper , chemistry , disease , organic chemistry
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. (H EPATOLOGY 1992;15:82–87).