title: Desferrioxamine-chelatable iron, a component of serum non-transferrin-bound iron, used for assessing chelation therapy.
abstract: This study introduces a method for monitoring a component of serum non-transferrin-bound iron (NTBI), termed "desferrioxamine-chelatable iron" (DCI). It is measured with the probe fluorescein-desferrioxamine (Fl-DFO), whose fluorescence is stoichiometrically quenched by iron. DCI was found in the serum of most patients with thalassemia major (21 of 27 tested, range 1.5-8.6 microM), but only in a minority of patients with hereditary hemochromatosis (8 of 95 samples from 39 patients, range 0.4-1.1 microM) and in none of 48 controls. The method was applied to monitoring the appearance of iron in the serum of patients under chelation therapy. Short-term (2 hours) follow-up of patients immediately after oral administration of deferriprone (L1) showed substantial mobilization of DCI into the serum (up to 10 microM within 30-60 minutes). The transfer of DCI from L1 to Fl-DFO was observed in vitro with preformed L1-iron complexes, and occurred even at L1/iron ratios exceeding 3:1. Simultaneous administration of oral L1 and intravenous DFO to patients abrogated the L1-mediated rise in DCI, consistent with the shuttling of iron from L1 to DFO in vivo. A similar iron transfer from L1 to apo-transferrin was observed in vitro, lending experimental support to the notion that L1 can shuttle iron in vivo to other high-affinity ligands. These results provide a rationale for using chelator combinations, with the highly permeant L1 acting as an intracellular chelator-shuttle and the less permeant DFO serving as an extracellular iron sink. Potential applications of the DCI assay may be for studying chelator action and as an index of patient chelation status.
authors.affiliation: Department of Biological Chemistry, Institute of Life Sciences, Hebrew University of Jerusalem, Israel. billb@vms.huji.ac.il
authors.forename: W
authors.initials: W
authors.lastname: Breuer
authors.forename: M J
authors.initials: MJ
authors.lastname: Ermers
authors.forename: P
authors.initials: P
authors.lastname: Pootrakul
authors.forename: A
authors.initials: A
authors.lastname: Abramov
authors.forename: C
authors.initials: C
authors.lastname: Hershko
authors.forename: Z I
authors.initials: ZI
authors.lastname: Cabantchik
mesh_terms: D000293:Adolescent; D000328:Adult; D001059:Apoproteins / Q000378:metabolism; D002138:Calibration; D015913:Chelation Therapy; D002648:Child; D000077543:Deferiprone; D003676:Deferoxamine / Q000378:metabolism* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D019793:Fluorescein / Q000737:chemistry; D006801:Humans; D007501:Iron / Q000097:blood*; D007502:Iron Chelating Agents / Q000378:metabolism* / Q000627:therapeutic use; D019190:Iron Overload / Q000097:blood / Q000628:therapy*; D007700:Kinetics; D008856:Microscopy, Fluorescence / Q000379:methods*; D011728:Pyridones / Q000627:therapeutic use; D014168:Transferrin / Q000378:metabolism
chemical_list: D001059:Apoproteins; D007502:Iron Chelating Agents; D011728:Pyridones; D014168:Transferrin; D000077543:Deferiprone; D007501:Iron; D003676:Deferoxamine; D019793:Fluorescein