2-2--azino-di-(3-ethylbenzothiazoline)-6-sulfonic-acid and phenoxy-radical

Laccases (EC 1.10.3.2) catalyze oxidation of phenolic groups in lignin to phenoxyl radicals during reduction of O

Topics: Benzothiazoles; Catalysis; Cyclic N-Oxides; Electron Spin Resonance Spectroscopy; Fungal Proteins; Laccase; Lignin; Oxidation-Reduction; Phenols; Phthalimides; Sordariales; Sulfonic Acids; Trametes; Triazoles

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 HBED 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 HBED facilitates Fe(II) oxidation but blocks O2(.-)-induced reduction of Fe(III) and consequently pre-empts production of .OH or hypervalent iron through the Haber-Weiss reaction cycle. The efficacy of HBED 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. HBED also provided cytoprotection against toxicity of H2O2 and t-BuOOH. Our results show that HBED 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.

Topics: Animals; Antioxidants; Benzothiazoles; Cell Death; Cell Line; Cell Survival; Chromans; Cricetinae; Cricetulus; Cyclic N-Oxides; Cytoprotection; Edetic Acid; Electron Spin Resonance Spectroscopy; Hydrogen; Hydrogen Peroxide; Hydroxyl Radical; Iron Chelating Agents; Oxidation-Reduction; Oxygen; Phenols; Spectrophotometry; Spin Labels; Sulfonic Acids; Superoxides; tert-Butylhydroperoxide