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Antioxidant balance and free radical generation in vitamin E-deficient mice after dermal exposure to cumene hydroperoxide.

Authors
Shvedova-AA; Kisin-ER; Murray-AR; Kommineni-C; Castranova-V; Mason-RP; Kadiiska-MB; Gunther-MR
Source
Chem Res Toxicol 2002 Nov; 15(11):1451-1459
NIOSHTIC No.
20022942
Abstract
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.
Keywords
Peroxides; Chemical-industry-workers; Polymers; Plastics; Fiberglass-industry; Pharmaceuticals; In-vivo-study; Animal-studies; Laboratory-animals; Skin-exposure
Contact
Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505, USA
CODEN
CRTOEC
CAS No.
80-15-9
Publication Date
20021101
Document Type
Journal Article
Email Address
ats1@cdc.gov
Fiscal Year
2003
NTIS Accession No.
NTIS Price
Issue of Publication
11
ISSN
0893-228X
NIOSH Division
HELD
Priority Area
Disease and Injury: Allergic and Irritant Dermatitis
Source Name
Chemical Research in Toxicology
State
WV
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