Deferoxamine inhibition of Cr(V)-mediated radical generation and deoxyguanine hydroxylation: ESR and HPLC evidence.
Shi X; Sun X; Gannett PM; Dalal NS
Arch Biochem Biophys 1992 Mar; 293(2):281-286
The effectiveness of deferoxamine in inhibiting chromium (7440473) (Cr) related radical formation was studied using Cr(V) induced decomposition of simple organic hydroperoxides. Electron spin resonance (ESR) and high performance liquid chromatography (HPLC) were used to study free radical generation in reactions of Cr(V) with hydrogen-peroxide and organic hydroperoxides. ESR showed that deferoxamine can reduce the concentration of the Cr(V) intermediate when formed in the reduction of Cr(VI) by NAD(P)H or a flavoenzyme glutathione-reductase/NADH. Deferoxamine also inhibited Cr(V) mediated hydroxyl radical generation from hydrogen-peroxide, and Cr(V) mediated alkyl and alkoxy radical formation from t-butyl- hydroperoxide and cumene-hydroperoxide. HPLC revealed that hydroxyl radicals generated by the Cr(VI)/flavoenzyme/NAD(P)H enzymatic system reacted with 2'-deoxyguanine to the DNA damage marker 8- hydroxy-2'-deoxyguanine. Deferoxamine effectively inhibited the formation of 8-hydroxy-2'-deoxyguanine as well. The authors conclude that deferoxamine has potential as a therapeutic agent against Cr(VI) genotoxicity.
NIOSH-Publication; NIOSH-Cooperative-Agreement; Chromates; Chromatographic-analysis; Free-radical-generation; Oxidation-reduction-reactions; Chelating-agents; Organic-peroxides; Liquid-chromatography; Free-radical-generation; Free-radicals; Chromium-compounds; DNA-damage
N. S. Dalal, Department of Chemistry and t&ho01 of Pharmacy, West Virginia University, Morgantown, West Virginia 26506
MIR 28-93; Cooperative-Agreement-Number-U60-CCU-306149
Archives of Biochemistry and Biophysics
Center to Protect Workers' Rights