Chelator-facilitated removal of iron from transferrin: relevance to combined chelation therapy.

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Devanur LD, Evans RW, Evans PJ, Hider RC

Chelator-facilitated removal of iron from transferrin: relevance to combined chelation therapy.

Biochem J. 2008 Jan 15;409(2):439-47.

PubMed ID

17919118 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Deferasirox	Iron	Small molecule	Humans	Yes	Chelator	Details