Oxygen-based free radical generation by ferrous ions and deferoxamine.
Deferoxamine accelerates the autooxidation of iron as measured by the rapid disappearance of Fe2+, the associated appearance of Fe3+, and the uptake of oxygen. Protons are released in the reaction. The formation of H2O2 was detected by the horseradish peroxidase-catalyzed oxidation of scopoletin, and the formation of hydroxyl radicals (OH.) was suggested by the formation of the OH. spin trap adduct (DMPO/OH). with the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and the generation of the methyl radical adduct on the further addition of dimethyl sulfoxide. (DMPO/OH). adduct formation was inhibited by catalase but not by superoxide dismutase. The oxidant formed converted iodide to a trichloroacetic acid-precipitable form (iodination) and was bactericidal to logarithmic phase Escherichia coli. Both iodination and bactericidal activity was inhibited by catalase and by OH. scavengers, but not by superoxide dismutase. Iodination was optimal in 5 x 10(-4) M acetate buffer, pH 5.0, and when the Fe2+ and deferoxamine concentrations were equimolar at 10(-4) M. Fe2+ could not be replaced by Fe3+, Co2+, Zn2+, Ca2+, Mg2+, or Mn2+, or deferoxamine by EDTA, diethylenetriaminepentaacetic acid, or bathophenanthroline. These findings indicate that Fe2+ and deferoxamine can act as an oxygen radical generating system, which may contribute to its biological effects in vitro and in vivo.
Klebanoff
S J
SJ
Department of Medicine, University of Washington, Seattle 98195.
Waltersdorph
A M
AM
Michel
B R
BR
Rosen
H
H
D002374:Catalase / Q000378:metabolism; D002413:Cations, Divalent; D003676:Deferoxamine; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006861:Hydrogen Peroxide / Q000032:analysis; D007501:Iron; D007700:Kinetics; D010084:Oxidation-Reduction; D013482:Superoxide Dismutase / Q000378:metabolism
D002413:Cations, Divalent; D005609:Free Radicals; D006861:Hydrogen Peroxide; D007501:Iron; D002374:Catalase; D013482:Superoxide Dismutase; D003676:Deferoxamine