Copper toxicosis and tolerance in the rat. I‐changes in copper content of the liver and kidney

Rats can tolerate toxic copper diets; the extent of this adaptation and the changes that take place in the liver and kidney with respect to copper are studied. Rats were fed diets containing 3000-6000 mg/kg copper for 15 weeks and groups were killed at regular intervals. Their livers and kidneys were examined for pathological changes and for their copper content. Liver copper rose rapidly in the 3000 mg/kg trial to 4780 +/- 636 micrograms/g copper between 4 and 5 weeks with marked liver damage. Stainable copper protein was present at 2 weeks in the hepatocytes but had disappeared by 5 weeks. Liver copper subsequently fell with recovery by 15 weeks. Kidney copper rose to plateau from 4 weeks. Stainable copper protein was present from 2 weeks in the cells of the proximal tubules and was apparently excreted. Tubular necrosis occurred at 4-5 weeks followed by regeneration. In the 6000 mg/kg trial the toxicosis was prolonged. Copper toxicosis in the rat can be a temporary phenomenon during the transformation of copper protein synthesis in the liver from a stainable to a non stainable form. Adaptation occurs after the removal of excess liver copper, facilitated probably by renal excretion, and the animals become tolerant.