Iron chelators, combinations

A permeable reactive barrier (PRB) is defined as an in situ method for remediating contaminated groundwater that combines a passive chemical or biological treatment zone with subsurface fluid flow management. Treatment media may include zero-valent iron, chelators, sorbents, and microbes to address a wide variety of groundwater contaminants, such as chlorinated solvents, other organics,... 

Iron(III) citrate, " " or iron(III) ammonium citrate, is the usual vehicle for administering supplementary iron to an iron-deficient patient, for inducing iron-overload in rats or other creatures prior to testing the efficacy of iron chelators, or for introducing the isotope Fe for metabolic tracer studies. Stability constants for the aqueous iron(III)-citrate system have been established. " The 2 1 complex is claimed to be the dominant species in iron(III)/citrate/DMF systems. " There has been a very qualitative study of the incorporation of iron into transferrin from iron citrate. " Iron(III) citrate reacts relatively slowly with the aluminum(III)-transferrin complex to give the thermodynamically strongly favored combination of iron(III)-transferrin with aluminum(lll) citrate. " The mechanism of iron uptake from citrate complexes in cells has been briefly discussed. An octa-iron citrate complex appears in Section 5.4.5.4.3 below. 

Experiments performed in vitro revealed that in contrast to DFO, which has a major cytotoxic effect only on trophozoites and early schizonts of P. falciparum, reversed siderophores have a cytotoxic effect on ring-stage and cytostatic effects on trophozoites and schizonts . These observations provided the basis for studying combinations of iron chelators for antimalarial therapy. When DFO is added to malaria parasites cultured in erythrocytes in combination with the more lipophilic and more permeate reversed siderophore 66, a strong synergistic inhibitory effect on parasite growth is observed. This effect may result from the different speeds of permeation of the two chelators... 

Several studies have investigated the effect of chelators on the Fenton reaction. Addition of chelators to Fe(III)-H202 systems allows for effective degradation at near-neutral pH values [17,23,61], Much of the influence of the iron chelators stems from increased solubility of iron species at higher pH values. These chelators were also effective for combined Fenton bioremediation treatment because they eliminate the need for low pH, which can harm useful bacteria. 

An orally effective iron chelator now under clinical investigation, deferiprone (1,2-dimethyl-3-hydroxypyridin-4-one), may be of value in patients with thalassemia major who are unable or unwilling to receive deferoxamine. Combination therapy with deferoxamine also is under investigation. 

The use of iron chelators has been reviewed [3 ] and some articles have provided a practical summary comparison of today s leading chelating drugs [4 , 5 ] (see Table 1). The use of combinations of these drugs may lessen some problems or create others [SEDA 31, 399]. 

Porter JB, Taher AT, Cappellini MD, Vichinsky EP. Ethical issues and risk/benefit assessment of iron chelation therapy advances with deferiprone/deferoxamine combinations and concerns about the safety, efficacy and costs of deferasirox [Kontoghiorghes GJ, Hemoglobin 2008 32 (1-2) 1-15]. Hemoglobin 2008 32(6) 601-7. 

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