Iron and dioxygen chemistry is an important route to initiation of biological free radical oxidations: An electron paramagnetic resonance spin trapping study

Iron can be a detrimental catalyst in biological free radical oxidations. Because of the high physiological ratio of [O-2]/[H2O2] (greater than or equal to 10(3)), we hypothesize that the Fenton reaction with pre-existing H2O2 is only a minor initiator of free radical oxidations and that the major initiators of biological fret radical oxidations are the oxidizing species formed by the reaction of Fe2+ with dioxygen. We have employed electron paramagnetic resonance spin trapping to examine this hypothesis. Free radical oxidation of: 1) chemical (ethanol, dimethyl sulfoxide); 2) biochemical (glucose, glyceraldehyde); and 3) cellular (L1210 murine leukemia cells) targets were examined when subjected to an aerobic Fenton (Fe2+ + H2O2 + O-2) or an aerobic (Fe2+ + O-2) system. As anticipated, the Fenton reaction initiates radical formation in all the above targets. Without pre-existing H2O2, however, Fe2+ and O-2 also induce substantial target radical formation. Under various experimental ratios of [O-2]/[H2O2] (1-100 with [O-2] approximate to 250 mu M), we compared the radical yield from the Fenton reaction vs. the radical yield from Fe2+ + O-2 reactions. When [O-2]/[H2O2] < 10, the Fenton reaction dominates target molecule radical formation; however, production of target-molecule radicals via the fenton reaction is minor when [O-2]/[H2O2] greater than or equal to 100. Interestingly, when L1210 cells are the oxidation targets, Fe2+ + O-2 is observed to be responsible for formation of nearly all of the cell-derived radicals detected, no matter the ratio of [O-2]/[H2O2]. Our data demonstrate that when [O-2]/[H2O2] greater than or equal to 100, Fe2+ + O-2 chemistry is an important route to initiation of detrimental biological free radical oxidations, (C) 1999 Elsevier Science Inc.