ABSTRACT
Iron-catalyzed tissue damage involves a series of physiological events, and therefore many therapeutic interventions have been proposed to interrupt the process at various steps in the cascade. In order to limit iron-catalyzed tissue damage via the removal of reactive iron, these compounds should be preferably high affinity, hexadentate ligands. The toxicity of iron is closely linked to its ability to transfer electrons and to catalyze the formation of other reactive species, specifically oxygen and lipid derived reactive compounds, leading to the subsequent destruction of biomolecules. Limiting the availability of free iron can be accomplished either by chelation therapy or by inhibiting its release from endogenous iron-containing compounds. The two naturally occurring iron-binding proteins, transferrin and lactoferrin, are effective chelators of iron and may act as endogenous buffers against the deleterious consequences of free iron. In addition to its intrinsic toxicity, hydrogen peroxide can be involved in liberation of iron from heme-containing compounds such as myoglobin and hemoglobin.
