Iron and Copper Interact during Their Uptake and Deposition in the Brain and other Organs of Developing Rats Exposed to Dietary Excess of the Two Metals

This study examined the effect of iron and copper loading on rat brain, liver, kidney, femur, blood and plasma concentrations of these metals and iron transport into the organs during development. Dams were fed control diets or iron-loaded diets (20 g/kg carbonyl iron) with either distilled water or copper-loaded water (350 mg/L) beginning at d 20 of pregnancy. The weanlings also had access to the diets and water supply and were examined at 15, 21 and 63 d of age. The iron content of the liver was 17- to 30-fold greater in iron-loaded rats than in controls, whereas liver, kidney and plasma copper levels generally were lower. Iron loading alone did not increase brain iron concentrations, suggesting the blood-brain barrier is already developed at birth. However, dual loading of iron and copper resulted in elevated concentrations of brain non-heme iron and copper in 15- and 63-d-old rats compared with animals loaded with iron alone. These results suggest that brain iron uptake mechanisms may be different when excess copper is present. Liver nonheme iron was also greater in copper-loaded rats, irrespective of iron status. However, kidney iron concentrations generally were not affected by dietary copper. In rats fed the copper-containing diet, the uptake of iron into brain and liver was significantly lower than in those fed the control diet, suggesting that copper loading can decrease iron uptake into organs. It is concluded that combined dietary supplementation with iron and copper can alter the metabolism of each metal. These changes are age and organ dependent. Developing rats may be very susceptible to these combined overload states because significant effects are seen in early adulthood.