Influence of iron-saturation of plasma transferrin in iron distribution in the brain

Based on the evidence that iron distribution in the peripheral tissues is changed by iron-saturation of plasma transferrin, the influence of iron-saturation of plasma transferrin in iron delivery to the brain was examined. Mouse plasma was pre-incubated with ferric chloride in citrate buffer to saturate transferrin and then incubated with (59)FeCl(3). Peak retention time of (59)Fe was transferred from the retention time of transferrin to that of mercaptalbumin, suggesting that iron may bind to albumin in the plasma in the case of iron-saturation of transferrin. When mice were intravenously injected with ferric chloride in citrate buffer 10 min before intravenous injection of (59)FeCl(3), 59Fe concentration in the plasma was remarkably low. (59)Fe concentration in the liver of iron-loaded mice was four times higher than in control, while 59Fe concentration in the brain of iron-loaded mice was approximately 40% of that of control mice. Twenty-four hours after intravenous injection of (59)FeCl(3), brain autoradiograms also showed that (59)Fe concentrations in the brain of iron-loaded mice were approximately 40-50% of those of control mice in all brain regions tested except the choroid plexus, in which (59)Fe concentration was equal. These results suggest that the fraction of non-transferrin-bound iron is engulfed by the liver, resulting in the reduction of iron available for iron delivery to the brain in iron-loaded mice. Transferrin-bound iron may be responsible for the fraction of iron in circulation that enters the brain.