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Blood, 1 February 2001, Vol. 97, No. 3, pp. 792-798
RED CELLS
Desferrioxamine-chelatable iron, a component of serum
non-transferrin-bound iron, used for assessing chelation
therapy
William Breuer,
Marieke J. J. Ermers,
Pensri Pootrakul,
Ayala Abramov,
Chaim Hershko, and
Z. Ioav Cabantchik
From the Department of Biological Chemistry, Institute
of Life Sciences, Hebrew University of Jerusalem, Israel; Utrecht
University Medical School, The Netherlands; Thalassemia Research
Center, Institute of Science and Technology for Research and
Development, Mahidol University, Salaya Campus, Nakornpathom, Thailand;
and Department of Pediatrics and Department of Internal Medicine,
Shaare Zedek Medical Center, Jerusalem, Israel.
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 µM),
but only in a minority of patients with hereditary hemochromatosis (8 of 95 samples from 39 patients, range 0.4- 1.1 µM) 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 to10 µM 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.
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