One-Electron Reduction of chromium(VI) by Alpha-Lipoic Acid and Related Hydroxyl Radical Generation, dG Hydroxylation and Nuclear Transcription Factor-kB Activation

Details

• Personal Author:
  Chen F ; Rojanasakul Y ; Shi X ; Ye J ; Zhang X
• Description:
  Reaction of chromium(VI) with a-lipoic acid (reduced form, also called 1,2-dithiolane-3-pentanoic acid) generated Cr(V) and hydroxyl radical (.OH) as measured by electron spin resonance and ESR spin trapping. 5,5-Dimethyl-1-pyrroline was used as a spin trapping agent. Catalase inhibited the .OH generation and enhanced the Cr(V) formation. Superoxide dismutase had an opposite effect. H2O2enhanced the .OH generation and decreased the Cr(V) formation in a dose-dependent manner. Metal chelators, EDTA, diethylenetriaminepentaacetic acid, deferoxamine, and 1,10-phenanthroline inhibited .OH radical generation in the order of EDTA > 1,10-phenanthroline > DTPA > deferoxamine. Oxygen consumption measurements indicated that molecular oxygen was used to generate .OH radical in the mixture of Cr(VI) and a-lipoic acid. H2O2and superoxide radical (O2-) were involved as reactive intermediates. The .OH radical was generated via Cr(V)-mediated Fenton-like reaction (Cr(V) + H2O2--> Cr(VI) + OH-+.OH). HPLC measurements show that the .OH radical generated by this reaction is capable of generating 8-hydroxyl-2'-deoxyguanosine from 2-deoxyguanosine. Incubation of Cr(VI) with cultured Jurkat cells resulted in an activation of DNA binding activity of the nuclear factor (NF)-kB. Addition of a-lipoic acid enhanced the NF-kB activation, while the .OH radical scavenger, sodium formate, inhibited it, showing that a-lipoic acid enhanced Cr(VI)-induced NF-kB activation via free radical reactions. The results indicate that while a-lipoic acid is considered to be an antioxidant, it may be a cellular one-electron Cr(VI) reductant and could be involved in the mechanism of Cr(VI)-induced carcinogenesis. [Description provided by NIOSH]
• Subjects:
  Antioxidants Carcinogens Chromium Metals Metals, Heavy Occupational Health Respiratory Tract Diseases Safety
• Keywords:
  Cell-function Cellular-uptake Chromium-compounds Heavy-metals Hydroxylation-reactions Metal-compounds Metallic-compounds Oxidation-reduction-reactions Oxidative-processes Pulmonary-system-disorders Respiratory-system-disorders

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• ISSN:
  0003-9861
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Maryland ; OSHA Region 3 ; Pennsylvania ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  165-172
• Volume:
  338
• Issue:
  2
• NIOSHTIC Number:
  nn:20033957
• Citation:
  Arch Biochem Biophys 1997 Feb; 338(2):165-172
• Contact Point Address:
  Xianglin Shi, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia, 26505
• CAS Registry Number:
  Chromium(6+) (CAS RN 18540-29-9) ; Glutathione (CAS RN 70-18-8) ; L-Ascorbic acid (CAS RN 50-81-7)
• Federal Fiscal Year:
  1997
• Peer Reviewed:
  True
• Source Full Name:
  Archives of Biochemistry and Biophysics
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:0ff363e997f9de6a95b38c359aa5a2804c3d4a11cdc8f90f134003b204838e7c26e1bb36833ea4d273880dbc53d87e162f6aea7fc1a62a80f932d16e3934ef3e
• Download URL:
  https://stacks.cdc.gov/view/cdc/189353/cdc_189353_DS1.pdf
• File Type:
  [PDF - 153.62 KB ]