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Please use this identifier to cite or link to this item: http://bura.brunel.ac.uk/handle/2438/4267

Title: Chelator-facilitated removal of iron from transferrin: Relevance to combined chelation therapy
Authors: Devanur, LD
Evans, RW
Evans, PJ
Hider, RC
Keywords: Deferiprone
Desferrioxamine (DFO)
Hydroxypyridin-4-one (HPO)
Iron chelation
Scavenging activity
Publication Date: 2008
Publisher: Portland Press
Citation: Biochemical Journal. 409(2): 439-447
Abstract: Current iron chelation therapy consists primarily of DFO (desferrioxamine), which has to be administered via intravenous infusion, together with deferiprone and deferasirox, which are orally-active chelators. These chelators, although effective at decreasing the iron load, are associated with a number of side effects. Grady suggested that the combined administration of a smaller bidentate chelator and a larger hexadentate chelator, such as DFO, would result in greater iron removal than either chelator alone [Grady, Bardoukas and Giardina (1998) Blood 92, 16b]. This in turn could lead to a decrease in the chelator dose required. To test this hypothesis, the rate of iron transfer from a range of bidentate HPO (hydroxypyridin-4-one) chelators to DFO was monitored. Spectroscopic methods were utilized to monitor the decrease in the concentration of the Fe–HPO complex. Having established that the shuttling of iron from the bidentate chelator to DFO does occur under clinically relevant concentrations of chelator, studies were undertaken to evaluate whether this mechanism of transfer would apply to iron removal from transferrin. Again, the simultaneous presence of both a bidentate chelator and DFO was found to enhance the rate of iron chelation from transferrin at clinically relevant chelator levels. Deferiprone was found to be particularly effective at ‘shuttling’ iron from transferrin to DFO, probably as a result of its small size and relative low affinity for iron compared with other analogous HPO chelators.
URI: http://bura.brunel.ac.uk/handle/2438/4267
ISSN: 0264-6021
Appears in Collections:Biological Sciences
Dept of Life Sciences Research Papers

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