A number of iron-chelating agents are currently being considered as orally active alternatives to desferrioxamine (DFO), the therapeutic agent for the treatment of body iron overload that is available at present. These include bidentate hydroxypyridinones (HPO), tridentate desferrithiocin (DFT) analogues and hexadentate aminocarboxylate (HBED) chelators. All chelating agents have the potential to induce toxic effects when iron homoeostasis is affected within the body. This can arise when the absorption, distribution and utilization of iron is affected. Alternatively, chelating agents can induce toxicity by directly interfering with iron-dependent metalloenzymes located within the body. These effects are, however, mainly localized to non-haem enzymes such as ribonucleotide reductase and lipoxygenase. The resultant iron complexes also have the ability to induce toxicity. Depending on the coordination geometry and donor atoms associated with the metal centre, redox cycling of the iron centre with the corresponding generation of free radicals can result.
Therapeutic iron chelators and their potential side-effects
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C. Rice-Evans, B. Halliwell, G.G. Lunt, S. Singh, Hh Khodr, M. I. Taylor, R. C. Hider; Therapeutic iron chelators and their potential side-effects. Biochem Soc Symp 1 November 1995; 61 127–137. doi: https://doi.org/10.1042/bss0610127
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