Deferoxamine inhibition of Cr(V)-mediated radical generation and deoxyguanine hydroxylation: ESR and HPLC evidence.
Electron spin resonance (ESR) and high-performance liquid chromatography (HPLC) techniques were utilized to investigate the effect of deferoxamine on free radical generation in the reaction of Cr(V) with H2O2 and organic hydroperoxides. ESR measurements demonstrated that deferoxamine can efficiently reduce the concentration of the Cr(V) intermediate as formed in the reduction of Cr(VI) by NAD(P)H or a flavoenzyme glutathione reductase/NADH. ESR spin trapping studies showed that deferoxamine also inhibits Cr(V)-mediated .OH radical generation from H2O2, as well as Cr(V)-mediated alkyl and alkoxy radical formation from t-butyl hydroperoxide and cumene hydroperoxide. HPLC measurements showed that .OH radicals generated by the Cr(VI)/flavoenzyme/NAD(P)H enzymatic system react with 2'-deoxyguanine to form 8-hydroxy-2'-deoxyguanine (8-OHdG), a DNA damage marker. Deferoxamine effectly inhibited the formation of 8-OHdG also.
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Department of Chemistry, West Virginia University, Morgantown 26506.
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Gannett
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D000818:Animals; D002417:Cattle; D002840:Chromates / Q000737:chemistry / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003676:Deferoxamine / Q000494:pharmacology*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000737:chemistry; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006861:Hydrogen Peroxide / Q000737:chemistry; D006878:Hydroxides / Q000737:chemistry*; D017665:Hydroxyl Radical; D006900:Hydroxylation / Q000187:drug effects; D010084:Oxidation-Reduction
D002840:Chromates; D005609:Free Radicals; D006878:Hydroxides; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide; D003849:Deoxyguanosine; D003676:Deferoxamine