Hepatic iron accumulation in copper-deficient rats

Studies of anaemia and tissue iron distribution were carried out in copper-deficient rats and pair-fed control animals given Fe orally or parenterally in varying doses. The anaemia of Cu deficiency was partially but incompletely corrected by oral Fe supplementation of one- to five-fold normal dietary levels or by intramuscular Fe supplementation. Serum Fe increased in Cu-deficient animals as the dose of supplemental Fe was increased. Hepatic Fe accumulation occurred in Cu-deficient rats which were administered with either oral Fe in two- to five-fold excess or low doses of intramuscular Fe. This difference was not seen in animals receiving high doses of intramuscular Fe, but similar relative differences were seen in Cu-deficient and Cu-replete rats which had been given no Fe supplementation. Duodenal Fe was not increased in Cu deficiency. Bone marrow Fe was present in Cu-deficient animals receiving either parenteral or oral Fe supplementation. Present studies suggest that a decrease in caeruloplasmin (EC 1.16.3.1) activity does not wholly explain the anaemia of Cu deficiency. Fe accumulation may be restricted to the liver, suggesting that Cu may be required for normal intracellular Fe metabolism.