D-penicillamine prevents the development of hepatitis in Long-Evans Cinnamon rats with abnormal copper metabolism.
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.
Laboratory of Pathology, Hokkaido University School of Medicine, Sapporo, Japan.
Y
Y
Togashi
Y
Y
Li
J H
JH
Kang
N
N
Takeichi
Y
Y
Fujioka
K
K
Nagashima
H
H
Kobayashi
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002614:Chelating Agents / Q000494:pharmacology*; D003300:Copper / Q000378:metabolism*; D005260:Female; D006520:Hepatitis, Animal / Q000235:genetics / Q000517:prevention & control*; D006651:Histocytochemistry / Q000379:methods; D008297:Male; D008661:Metabolism, Inborn Errors / Q000097:blood / Q000188:drug therapy*; D010396:Penicillamine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011922:Rats, Mutant Strains; D013194:Staining and Labeling
D002614:Chelating Agents; D003300:Copper; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D010396:Penicillamine