Antioxidant Balance and Free Radical Generation in Vitamin E-Deficient Mice After Dermal Exposure to Cumene Hydroperoxide

Details

• Personal Author:
  Castranova, Vincent ; Gunther MR ; Kadiiska MB ; Kisin ER ; Kommineni C ; Mason RP ; Murray AR ; Shvedova AA
• Description:
  Organic peroxides are widely used in the chemical industry as initiators of oxidation for the production of polymers and fiber-reinforced plastics, in the manufacture of polyester resin coatings, and pharmaceuticals. Free radical production is considered to be one of the key factors contributing to skin tumor promotion by organic peroxides. In vitro experiments have demonstrated metal-catalyzed formation of alkoxyl, alkyl, and aryl radicals in keratinocytes incubated with cumene hydroperoxide. The present study investigated in vivo free radical generation in lipid extracts of mouse skin exposed to cumene hydroperoxide. The electron spin resonance (ESR) spin-trapping technique was used to detect the formation of alpha-phenyl-N-tert-butylnitrone (PBN) radical adducts, following intradermal injection of 180 mg/kg PBN. It was found that 30 min after topical exposure, cumene hydroperoxide (12 mmol/kg) induced free radical generation in the skin of female Balb/c mice kept for 10 weeks on vitamin E-deficient diets. In contrast, hardly discernible radical adducts were detected when cumene hydroperoxide was applied to the skin of mice fed a vitamin E-sufficient diet. Importantly, total antioxidant reserve and levels of GSH, ascorbate, and vitamin E decreased 34%, 46.5%. 27%, and 98%, respectively, after mice were kept for 10 weeks on vitamin E-deficient diet. PBN adducts detected by ESR in vitamin E-deficient mice provide direct evidence for in vivo free radical generation in the skin after exposure to cumene hydroperoxide. [Description provided by NIOSH]
• Subjects:
  Animals Biopharmaceutics Glass Laboratories Manufacturing And Industrial Facilities Occupational Health Peroxides Plastics Polymers Safety Skin

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• Keywords:
  Animal-studies Chemical-industry-workers Fiberglass-industry In-vivo-study Laboratory-animals Pharmaceuticals Skin-exposure
• ISSN:
  0893-228X
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  15
• Issue:
  11
• NIOSHTIC Number:
  nn:20022942
• Citation:
  Chem Res Toxicol 2002 Nov; 15(11):1451-1459
• Contact Point Address:
  Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505, USA
• Email:
  ats1@cdc.gov
• CAS Registry Number:
  Cumene hydroperoxide (CAS RN 80-15-9)
• Federal Fiscal Year:
  2003
• NORA Priority Area:
  Disease and Injury: Allergic and Irritant Dermatitis
• Peer Reviewed:
  True
• Source Full Name:
  Chemical Research in Toxicology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:983bca2b5947daafc892983bc1bf792124bb1c0222e0b6a08c662aff5c8fe1bda893c3d0e2090ec83ae0ec75308b63b491dd000071c066e27d218ddfebe09e49
• Download URL:
  https://stacks.cdc.gov/view/cdc/199548/cdc_199548_DS1.pdf
• File Type:
  [PDF - 150.00 KB ]