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NUTRIENT IRON TOXICI Résumé de rapport

Project ID: QLK1-CT-2002-00444
Financé au titre de: FP5-LIFE QUALITY
Pays: Switzerland

Redox-cycling of iron complexes and inhibition by nitrogen monoxide

The toxicity of iron is believed to originate from the reaction of a Fe(II) complex with hydrogen peroxide that produces HO". NO" slows the rate of the oxidation (as studied by stopped?flow spectrophotometry) of Fe(II) bound to citrate, atp and various aminopolycarboxylates by H2O2 by a factor between 10 and 100. The reaction of tert?butyl hydroperoxide with Fe(II) complexes is similarly inhibited by nitrogen monoxide. Generally, NO" replaces a water bound to iron(II), and the rate of oxidation is influenced by the rate of dissociation of the nitrogen monoxide from iron(II).

Iron(II) dithiocarbamate complexes are used to trap NO" in biological samples, and the resulting nitrosyliron(II)dithiocarbamate is detected and quantified by ESR. As the chemical properties of these compounds have been little studied, we investigated whether iron dithiocarbamate complexes can redox-cycle and produce O2"? and HO" radicals. The electrode potentials of iron complexes of N?(dithiocarboxy)sarcosine and N?methyl?D?glucamine dithiocarbamate as measured by cyclic voltammetry alow thermodynamically redox cycling, and the rates of oxidation by dioxygen and hydrogen peroxide and reduction by ascorbate, cysteine and glutathione are such that redox cycling is an efficient process. Again, NO" inhibits the oxidation of iron(II) dtcs and iron(II) mgd by H2O2.


Willem H. KOPPENOL, (Professor)
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