MECHANISM OF IRON CHELATION IN HYPERTRANSFUSED RAT - DEFINITION OF 2 ALTERNATIVE PATHWAYS OF IRON MOBILIZATION

  • 1 January 1978
    • journal article
    • research article
    • Vol. 92  (2) , 144-151
Abstract
The mechanism of action of 2 recently identified iron-chelating drugs, Ra [rhodotorulic acid] and CHA [cholylhydroxamic acid], was compared with that of 2 well-known chelating agents, DF [deferoxamine] and DTPA [diethylenetriamineepentaacetic acid], in hypertransfused rats labeled with selective parenchymal and RES cell radioiron probes. The existence of 2 alternative pathways for the in vivo chelation of iron was indicated. The 1st of these pathways involves the extracellular chelation of RES cell iron and its subsequent excretion in the urine. The 2nd pathway is concerned with the intracellular binding of hepatic parenchymal cell iron and its subsequent excretion in the bile. Iron chelation by DTPA is restriced to the 1st pathway: iron chelation by CHA is confined to the 2nd 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 cell iron. Hypertransfused rats are a simple and useful experimental model for the study of iron mobilization by chelating agents of potential clinical usefulness. 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.