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

Details

• Personal Author:
  Dalal NS ; Gannett PM ; Shi X ; Sun X
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Chelating Agents Chromates Chromatography Chromium DNA Free Radicals Occupational Health Safety
• Keywords:
  Chelating-agents Chromatographic-analysis Chromium-compounds DNA-damage Free-radical-generation Free-radicals Liquid-chromatography NIOSH-Cooperative-Agreement NIOSH-Publication Organic-peroxides Oxidation-reduction-reactions

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• ISSN:
  0003-9861
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  District of Columbia ; OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  281-286
• Volume:
  293
• Issue:
  2
• NIOSHTIC Number:
  nn:00205560
• Citation:
  Arch Biochem Biophys 1992 Mar; 293(2):281-286
• Contact Point Address:
  N. S. Dalal, Department of Chemistry and t&ho01 of Pharmacy, West Virginia University, Morgantown, West Virginia 26506
• CAS Registry Number:
  Chromium (CAS RN 7440-47-3)
• Federal Fiscal Year:
  1992
• NORA Priority Area:
  Pulmonary System Disorders
• Performing Organization:
  Center to Protect Workers' Rights
• Peer Reviewed:
  True
• Start Date:
  19900928
• Source Full Name:
  Archives of Biochemistry and Biophysics
• End Date:
  19970515
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:7c89d8c695c0535ddfd59fa5ac80a80da9dce036a696858ed5c4ce7fea981fe9f4fe28bfb4a0d79813efa27573e75e10ae0e20d1bbadf5037f5099e80511ee9f
• Download URL:
  https://stacks.cdc.gov/view/cdc/204440/cdc_204440_DS1.pdf
• File Type:
  [PDF - 630.00 KB ]