Comparative studies of enhanced iron-mediated production of hydroxyl radical by glutathione, cysteine, ascorbic acid, and selected catechols.
A sensitive electrochemical detection system was employed together with a specific salicylate hydroxylation assay to comparatively assess the effects of various substances on the iron-mediated generation of the hydroxyl radical (.OH). Hydroxyl radical production was found to be enhanced significantly by reduced glutathione, cysteine, ascorbic acid, and selected catechols, but not by mannitol, melatonin or tyramine. The data showed that over the range of concentrations examined, the augmented effects were linearly proportional to the amount of added reductant for a given amount of iron in the system. The pro-oxidant activity of thiols and ascorbate reduced and recycled iron providing both hydrogen peroxide (H2O2) and catalytic ferrous ions for augmented .OH production by the Fenton reaction. The enhanced production of .OH by catechols resulted from their oxidation either by molecular oxygen or ferric ions, with the accompanying formation of semiquinones, superoxide anion and H2O2. These data caution against therapeutic applications of thiols and ascorbate for ameliorating oxy-radical-induced tissue damage in environments where free redox-active metal ions may be present to function both as foci for site-specific peroxidative activity, and as catalysts to promote the pro-oxidant properties of certain endogenous reductants, thereby elevating rather than diminishing .OH levels.
Nappi
A J
AJ
Department of Biology, Loyola University Chicago, IL 60626, USA. anappi@orion.it.luc.edu
Vass
E
E
D001205:Ascorbic Acid / Q000494:pharmacology*; D002396:Catechols / Q000494:pharmacology*; D003545:Cysteine / Q000494:pharmacology*; D005978:Glutathione / Q000494:pharmacology*; D017665:Hydroxyl Radical / Q000378:metabolism*; D007501:Iron / Q000494:pharmacology*
D002396:Catechols; D017665:Hydroxyl Radical; D007501:Iron; D005978:Glutathione; D003545:Cysteine; D001205:Ascorbic Acid