Mechanisms for the shuttling of plasma non-transferrin-bound iron (NTBI) onto deferoxamine by deferiprone.

Translational Research : the Journal of Laboratory and Clinical Medicine
Patricia J EvansJ Porter

Abstract

In iron overload conditions, plasma contains non-transferrin bound iron species, collectively referred to as plasma NTBI. These include iron citrate species, some of which are protein bound. Because NTBI is taken into tissues susceptible to iron loading, its removal by chelation is desirable but only partial using standard deferoxamine (DFO) therapy. Speciation plots suggest that, at clinically achievable concentrations, deferiprone (DFP) will shuttle iron onto DFO to form feroxamine (FO), but whether NTBI chelation by DFO is enhanced to therapeutically relevant rates by DFP is unknown. As FO is highly stable, kinetic measurements of FO formation by high-performance liquid chromatography or by stopped-flow spectrometry are achievable. In serum from thalassemia major patients supplemented with 10 microM DFO, FO formation paralleled NTBI removal but never exceeded 50% of potentially available NTBI; approximately one third of NTBI was chelated rapidly but only 15% of the remainder at 20 h. Addition of DFP increased the magnitude of the slower component, with increments in FO formation equivalent to complete NTBI removal by 8 h. This shuttling effect was absent in serum from healthy control subjects, indicating no transferrin iron ...Continue Reading

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Citations

Jul 30, 2014·Hematology/oncology Clinics of North America·John B Porter, Maciej Garbowski
Dec 14, 2011·Hematology·Janet L Kwiatkowski
Nov 16, 2012·Blood Cells, Molecules & Diseases·Ashutosh LalElliott Vichinsky
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Jun 3, 2015·British Journal of Haematology·Evangelia Vlachodimitropoulou KoumoutseaJohn Porter
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May 18, 2016·Annals of the New York Academy of Sciences·Janet L Kwiatkowski
Jun 28, 2016·Translational Research : the Journal of Laboratory and Clinical Medicine·Maciej W GarbowskiJohn B Porter
Nov 29, 2016·European Journal of Haematology·Sebastian BotzenhardtAntje Neubert
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