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Phenol induced in vivo oxidative stress in skin: evidence for enhanced free radical generation, thiol oxidation and antioxidant depletion.

Murray-A; Kisin-E; Castranova-V; Kommineni-C; Gunter-MR; Shvedova-AA
Toxicologist 2001 Mar; 60(1):42
A variety of phenolic compounds are utilized in industry (e.g., for production of phenol-formaldehyde resins, paints and lacquers, cosmetics and pharmaceuticals). They can be toxin to skin (i.e., can cause rash, dermal inflammation, contact dermatitis, leucoderma, and/or cancer promotion). The biochemical mechaisms for dermal toxicity of phenolic compounds are not well understood. We hypothesized that enzymatic one-electron oxidation of phenol compounds, resulting in generation of phenoxyl radicals, may be an important contributor to dermal toxicity. To test this hypothesis, we monitored in vivo the formation of @-phenyl-N-tert-butylnitrone (PBN)-spin-trapped radical adducts by ESR spectroscopy, measured glutathione (GSH), protein thiols, vitamin E and total antioxidant reserves in skin of B6C3F1 mice topically treated with phenol and compared the responses with those produced by phenol in mice with diminished levels of GSH. We found that dermal exposure to phenol (3.5 mmol/kg, 100 ul on the shaved back, for 30 min) caused oxidation of GSH and protein thiols and decreased vitamin E and total antioxidant reserves in the skin. The magnitude of the phenol-induced generation of PBN-spin-trapped radical adducts in skin of mice with diminished levels of GSH (pre-treated with 1,3-bis (2-chloroethyl)-1-nitrosourea, BCNU, an inhibitor of glutathione reductase) was markedly higher compared to those treated with phenol alone. BCNU pre-treated mice also exhibited increased inflammatory cell infiltrates in skin after topical exposure to phenol. Since dermal exposure to phenol produced ESR-detectable PBN spin-trapped signals of lipid-derived radicals, we conclude that redox-cycling of a one-electron oxidation product of phenol, its phenoxyl radical, is involved in oxidative stress and dermal toxicity in vivo.
Phenols; In-vivo-studies; Oxidation; Stress; Thiols; Antioxidants
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The Toxicologist. Society of Toxicology 40th Annual Meeting, March 25-29, 2001, San Francisco, California