Mechanism of iron chelation in the hypertransfused rat: definition of two alternative pathways of iron mobilization

Abstract

The mechanism of action of two recently identified iron-chelating drugs, RA and CHA, was compared with that of two well-known chelating agents, DF and DTPA, in hypertransfused rats labeled with selective parenchymal and RE cell radioiron probes. The existence of two alternative pathways for the in vivo chelation of iron has been indicated by the present findings. The first of these pathways involves the extracellular chelation of RE cell iron and its subsequent excretion in the urine. The second pathway is concerned with the intracellular binding of hepatic parenchymal cell iron and its subsequent excretion in the bile. Iron chelation by DTPA is restricted to the first pathway, whereas iron chelation by CHA is confined to the second pathway. DF and RA have a dual effect and are able to enhance the urinary excretion of RE cell iron as well as the biliary excretion of hepatic parenchymal iron. Hypertransfused rats are a simple and useful experimental model for the study of iron mobilization by chelating agents of potential clinical usefulness. However, further studies are required to show whether the pathways of iron chelation identified in rats may represent the mechanism of iron chelation in patients with transfusional iron overload.