The effects of iron loading and iron deficiency on the tissue uptake of 64Cu during development in the rat

This study examined the uptake of 64Cu by the brain, liver and other organs during development in rats aged 15, 21 and 63 days fed low, normal and high iron diets, using either a solution of 64CuCl2 chelated with nitrilo-triacetic acid (NTA) or 64Cu-ceruloplasmin (64Cu-Cp). 64Cu-NTA uptake was higher in the brain, spleen, kidneys, femurs and red cells at 15 days than at the later ages, while the liver took up most of the 64Cu in 63-day-old rats over the 2 h of the study. The brain had similar levels of 64Cu-NTA uptake at 15 and 21 days, even though liver uptake significantly increased, suggesting that Cu-NTA uptake by the brain increases from 15 to 21 days. The brain took up a greater percent of the injected dose of 64Cu-Cp than 64Cu-NTA yet, in either case, brain uptake was lower than that of the other organs. Iron loaded rats had significantly higher uptake of non-ceruloplasmin-bound 64Cu in all the organs examined, for at least one of the three ages, when compared with control rats. However, iron deficiency produced little change. Iron loading has a greater effect on 64Cu-Cp uptake than 64Cu-NTA, decreasing 64Cu uptake in the brain, liver, kidneys and femurs. Iron deficiency only increased 64Cu-Cp uptake in the liver. These results suggest that the mechanism of copper uptake by the liver is still maturing during suckling in the rat, and that ceruloplasmin receptor numbers are down regulated by iron loading, thus providing evidence of a new link between iron and copper metabolism.