Enhancement of the Peroxidase-Mediated Oxidation of Butylated Hydroxytoluene to a Quinone Methide by Phenolic and Amine Compounds

Details

• Personal Author:
  Thompson DC ; Trush MA
• Description:
  We have recently demonstrated that butylated hydroxyanisole (BHA) markedly stimulates the peroxidase-dependent oxidation of butylated hydroxytoluene (BHT) to the potentially toxic BHT-quinone methide. Using both horseradish peroxidase and prostaglandin H synthase we now report the ability of a wide variety of compounds to stimulate peroxidase-dependent activation of BHT. These compounds include several phenolic compounds commonly present in pharmacologic preparations or occurring naturally in foods. The ability of a given compound to stimuate BHT oxidation was found to depend on the type of radical it forms upon peroxidase oxidation. Compounds which have been shown to form phenoxy radicals or nitrogen-centered cation radicals were observed to enhance BHT oxidation. Conversely, compounds which are known to form peroxy radicals or semiquinone radicals either inhibited or had no effect on BHT oxidation. Compounds which enhanced BHT oxidation (monitored by covalent binding of [14C]BHT to protein) were also observed to stimulate the formation of BHT-quinone methide and stilbenequinone. This suggested a common mechanism of interaction of these compounds with BHT. The stimulation of BHT covalent binding by BHA was also seen in various human and animal tissues using either arachidonic acid or hydrogen peroxide as substrate. The possible toxicologic implications of the enhancement of peroxidase-catalyzed BHT oxidation to BHT-quinone methide are discussed. [Description provided by NIOSH]
• Subjects:
  Amines Biochemistry Occupational Health Oxidants Safety Toxicology
• Keywords:
  Author Keywords: Butylated Hydroxytoluene Biochemical Effects Butylated Hydroxyanisole Food Additives Oxidation Oxidative Processes Peroxidase Phenolic Compounds Phenoxy Radical Quinone Methide
• ISSN:
  0009-2797
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Maryland ; North Carolina ; OSHA Region 3 ; OSHA Region 4
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  157-173
• Volume:
  72
• Issue:
  1
• NIOSHTIC Number:
  nn:20060070
• Citation:
  Chem-Biol Interact 1989 Nov; 72(1-2):157-173
• Contact Point Address:
  David C.Thompson, National Institute of Environmental Health Sciences, Laboratory of Molecular Biophysics (MD 14-03), P.O. Box 12233, Research Triangle Park, NC 27709, U.S.A.
• CAS Registry Number:
  2,6-Di-tert-butyl-4-methylphenol (CAS RN 128-37-0)
• Federal Fiscal Year:
  1990
• Performing Organization:
  Johns Hopkins University, Baltimore, Maryland
• Peer Reviewed:
  True
• Start Date:
  19830701
• Source Full Name:
  Chemico-Biological Interactions
• End Date:
  19850630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:f0e98d9ec01a8eb649a353ddf23fd2b5c5b2f0cfcfb81a86589c99029832a6f5694d5bffa0325a571d56417a7104ca40baa409eb34b5bb43adc387226ccd91a3
• Download URL:
  https://stacks.cdc.gov/view/cdc/224101/cdc_224101_DS1.pdf
• File Type:
  [PDF - 890.18 KB ]