Antioxidant balance and free radical generation in vitamin E deficient mice after dermal exposure to cumene hydroperoxide.
Shvedova-AA; Kisin-ER; Kommineni-C; Mason-RP; Kadiiska-MB
Toxicologist 2000 Mar; 54(1):49
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 as antimicrobial agents in 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 tree radical generation in lipid extracts of mouse skin exposed to cumene hydroperoxicle. The electron spin resonance (ESR) spin-trapping technique was used to detect the formation of alfa-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 (12mmole/kg) induced free radical generation in the skin of female Balb/C mice (13-14 weeks old) kept for 10 weeks on vitamin E deficient diets. In contrast, no radical adducts were detected when cumene hydroperoxide was applied to the skin of mice fed a vitamin E sufficient diet. Important1y, levels of GSH and vitamin E in the skin of vitamin E deficient mice decreased 30% and 80%, respectively, compared to vitamin E sufficient controls. PBN adducts detected by ESR in vitamin E deficient mice provide direct evidence for in vivo tree radical generation in the skin after exposure to cumene hydroperoxide.
Antioxidants; Antioxidation; Free-radicals; Free-radical-generation; Laboratory-animals; Animals; Animal-studies; Exposure-levels; Exposure-assessment; Organic-peroxides; Oxidation; Polymers; Pharmaceuticals; Skin-tumors; In-vitro-studies; In-vivo-studies; Aryls
The Toxicologist. Society of Toxicology 39th Annual Meeting, March 19-23, 2000, Philadelphia, Pennsylvania