Multiple mechanisms account for lower plasma iron in young copper deficient rats

Copper deficiency lowers brain copper and iron during development. The reduced iron content could be due to hypoferremia. Experiments were conducted to evaluate plasma iron and "ferroxidase" hypotheses by determining copper and iron status of Holtzman albino rats following gestational/lactational copper deficiency. Copper deficient (Cu-) dams on treatment for 5 weeks, two of gestation and three of lactation, had markedly lower copper content of milk and mammary tissue, and lower milk iron. Newborn pups from Cu- dams had lower copper and iron concentrations. Compared to Cu+ pups, Cu- pups, analyzed between postnatal age (P) 0 and P26, were smaller, anemic, had lower plasma iron, cardiac hypertrophy, and near zero ceruloplasmin activity. Liver copper in Cu+ pups increased then decreased during development and major reductions were evident in Cu- pups. Liver iron in Cu+ pups decreased with age while nursing but increased after eating solid food. Liver iron was lower in Cu- pups at P0 and P13 and normal at P20 and P26. Small intestinal copper decreased with age in Cu+ pups and was lower in Cu- pups. Intestinal iron levels in Cu- pups were higher than Cu+ pups postweaning in some experiments. Reduction in plasma iron in Cu- pups is likely due to a decreased "ferroxidase" function leading to lower placental iron transport, a lower milk iron diet, and partial block in iron uptake from intestine but is not due to failure to mobilize hepatic iron, in contrast to older rats eating diet with adequate iron.