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

This study examined the uptake of Cu-64 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 tither a solution of (CuCl2)-Cu-64 chelated with nitrilo-triacetic acid (NTA) or Cu-64-ceruloplasmin (Cu-64-Cp). Cu-64-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 Cu-64 in 63-day-old rats over the 2 h of the study. The brain had similar levels of Cu-64-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 Cu-64-Cp than Cu-64-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 Cu-64 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 Cu-64-Cp uptake than Cu-64-NTA, decreasing (CU)-C-64 uptake in the brain, liver, kidneys and femurs. Iron deficiency only increased Cu-64-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.