Multifunctional antioxidant activity of HBED iron chelator

The use of N,N'-bis (2-hydroxybenzyl) ethylenediamine-N,N'-diacetic acid (HBED) for iron chelation therapy is currently being tested. Besides its affinity for iron, bioavailability, and efficacy in relieving iron overload, it is important to assess its anti- and/or pro-oxidant activity. To address these questions, the antioxidant/pro-oxidant effects of HEED in a cell-free solution and on cultured Chinese hamster V79 cells were studied using UV-VIS spectrophotometry, oximetry, spin trapping, and electron paramagnetic resonance (EPR) spectrometry. The results indicate that HEED facilitates Fe(II) oxidation but blocks O-2(.-)-induced reduction of Fe(III) and consequently pre-empts production of (OH)-O-. or hypervalent iron through the Haber-Weiss reaction cycle. The efficacy of HEED as a 1-electron donor (H-donation) was demonstrated by reduction of the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate)-derived nitrogen-centered radical cation (ABTS(.+)), accompanied by formation of a short-lived phenoxyl radical. HEED also provided cytoprotection against toxicity of H2O2 and t-BuOOH. Our results show that HEED can act both as a H-donating antioxidant and as an effective chelator lacking pro-oxidant capacity, thus substantiating its promising use in iron chelation therapy. (C) 2001 Elsevier Science Inc.