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Deferoxamine inhibition of Cr(V)-mediated radical generation and deoxyguanine hydroxylation: ESR and HPLC evidence.

Authors
Shi-X; Sun-X; Gannett-PM; Dalal-NS
Source
Arch Biochem Biophys 1992 Mar; 293(2):281-286
NIOSHTIC No.
00205560
Abstract
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.
Keywords
NIOSH-Publication; NIOSH-Cooperative-Agreement; Chromates; Chromatographic-analysis; Free-radical-generation; Oxidation-reduction-reactions; Chelating-agents; Organic-peroxides
CODEN
ABBIA4
CAS No.
7440-47-3
Publication Date
19920301
Document Type
Journal Article
Funding Amount
2937066
Funding Type
Cooperative Agreement
Fiscal Year
1992
NTIS Accession No.
NTIS Price
Identifying No.
Cooperative-Agreement-Number-U60-CCU-306149
Issue of Publication
2
ISSN
0003-9861
Priority Area
Pulmonary-system-disorders
Source Name
Archives of Biochemistry and Biophysics
State
DC
Performing Organization
Center to Protect Workers' Rights
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