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

Xianglin Shi; Xiaoya Sun; Peter M. Gannett; N. S. Dalal

doi:10.1016/0003-9861(92)90396-E

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

Xianglin Shi
, Xiaoya Sun
, Peter M. Gannett
, N. S. Dalal

Toxicology and Cancer Biology

Research output: Contribution to journal › Article › peer-review

74 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	281-286
Number of pages	6
Journal	Archives of Biochemistry and Biophysics
Volume	293
Issue number	2
DOIs	https://doi.org/10.1016/0003-9861(92)90396-E
State	Published - Mar 1992

Bibliographical note

Funding Information:
’ This research has been supported by the Department of the Interior’s Mineral Institute program administered by the Bureau of Mines through the Generic Mineral Technology Center for Respirable Dust under Grant G1135142 and by NIOSH Grant U60-CCU306149-01-1. ’ To whom correspondence and requests for reprints should be addressed.

Funding

’ This research has been supported by the Department of the Interior’s Mineral Institute program administered by the Bureau of Mines through the Generic Mineral Technology Center for Respirable Dust under Grant G1135142 and by NIOSH Grant U60-CCU306149-01-1. ’ To whom correspondence and requests for reprints should be addressed.

Funders	Funder number
Bureau of Mines	G1135142
Department of the Interior’s Mineral Institute
National Institute for Occupational Safety and Health	U60-CCU306149-01-1

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology

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10.1016/0003-9861(92)90396-E

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@article{c3a7fb0736f845b1b933069ffacb6ea2,

title = "Deferoxamine inhibition of Cr(V)-mediated radical generation and deoxyguanine hydroxylation: ESR and HPLC evidence",

abstract = "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.",

author = "Xianglin Shi and Xiaoya Sun and Gannett, \{Peter M.\} and Dalal, \{N. S.\}",

note = "Funding Information: {\textquoteright} This research has been supported by the Department of the Interior{\textquoteright}s Mineral Institute program administered by the Bureau of Mines through the Generic Mineral Technology Center for Respirable Dust under Grant G1135142 and by NIOSH Grant U60-CCU306149-01-1. {\textquoteright} To whom correspondence and requests for reprints should be addressed.",

year = "1992",

month = mar,

doi = "10.1016/0003-9861(92)90396-E",

language = "English",

volume = "293",

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AU - Gannett, Peter M.

AU - Dalal, N. S.

N1 - Funding Information: ’ This research has been supported by the Department of the Interior’s Mineral Institute program administered by the Bureau of Mines through the Generic Mineral Technology Center for Respirable Dust under Grant G1135142 and by NIOSH Grant U60-CCU306149-01-1. ’ To whom correspondence and requests for reprints should be addressed.

PY - 1992/3

Y1 - 1992/3

N2 - 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.

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

Abstract

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