Impaired hepatic copper homeostasis in Long-Evans Cinnamon rats: reduced biliary excretion of copper.

To explain the pathogenesis of excessive copper accumulation in Long-Evans Cinnamon (LEC) rats, regarded as one of the animal models for hepatic-type Wilson's disease, we measured copper contents in liver tissue and bile, serum total copper concentration, and ceruloplamin oxidase activity in LEC rats before and after the onset of spontaneous hepatitis. The copper contents in liver tissue of both 11-wk-old and 18-mo-old LEC rats were about 60 times the amounts in age-matched Wistar and Long-Evans Agouti rats. The biliary copper excretion in 11-wk-old LEC rats was significantly lower than that of the Long-Evans Agouti and Wistar rats that were the same age (27.9 and 41.4%, respectively). In 18-mo-old LEC rats, biliary copper excretion was lower than that in the Long-Evans Agouti rats that were the same age, but the finding was statistically not significant. Serum copper and ceruloplasmin levels were markedly reduced in LEC rats of both ages. These findings suggest that LEC rats have similar defects of biliary copper excretion as observed in patients with Wilson's disease.