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

Authors
Murray-A; Kisin-E; Castranova-V; Kommineni-C; Gunter-MR; Shvedova-AA
Source
Chem Res Toxicol 2007 Dec; 20(12):1769-1777
NIOSHTIC No.
20033259
Abstract
A variety of phenolic compounds are utilized in industry (e.g., for the production of phenol (PhOH)-formaldehyde resins, paints and lacquers, cosmetics, and pharmaceuticals). They can be toxic to skin, causing rash, dermal inflammation, contact dermatitis, depigmentation, and cancer promotion. The biochemical mechanisms for the dermal toxicity of phenolic compounds are not well understood. We hypothesized that topical PhOH exposure results in the generation of radicals, possibly via redox-cycling of phenoxyl radicals, which may be an important contributor to dermal toxicity via the stimulation of the induction and release of inflammatory mediators. To test this hypothesis, we (1) monitored in vivo the formation of PBN-spin-trapped radical adducts by ESR spectroscopy, (2) measured GSH, protein thiols, vitamin E, and total antioxidant reserves in the skin of B6C3F1 mice topically treated with PhOH, and (3) compared the responses with those produced by PhOH in mice with diminished levels of GSH. We found that dermal exposure to PhOH (3.5 mmol/kg, 100 mu L on the shaved back, for 30 min) caused oxidation of GSH and protein thiols and decreased vitamin E and total antioxidant reserves in skin. The magnitude of the PhOH-induced generation of PBN-spin-trapped radical adducts in the skin of mice with diminished levels of GSH (pretreated with BCNU, an inhibitor of glutathione reductase, or BSO, an inhibitor of gamma-glutamylcysteine synthetase) was markedly higher compared to radical generation in mice treated with PhOH alone. Topical exposure to PhOH resulted in skin inflammation. Remarkably, this inflammatory response was accelerated in mice with a reduced level of GSH. Epidermal mouse cells exposed to phenolic compounds showed the induction of early inflammatory response mediators, such as prostaglandin E, and IL- I. Since dermal exposure to PhOH produced ESR-detectable PBN spin-trapped signals of lipid-derived radicals, we conclude that this PhOH-induced radical formation is involved in oxidative stress and dermal toxicity in vivo.
Keywords
Phenols; In-vivo-studies; Oxidation; Stress; Thiols; Antioxidants; Biomarkers; Laboratory-animals; Animal-studies; Animals; Dermatitis; Skin-exposure
Contact
AA Shvedova, NIOSH, Div Hlth Effects Lab, Pathol & Physiol Res Branch, ML 2015,1095 Willowdale Rd Morgantown, Morgantown, WV 26505 USA
CODEN
CRTOEC
CAS No.
108-95-2
Publication Date
20071201
Document Type
Journal Article
Fiscal Year
2008
NTIS Accession No.
NTIS Price
Issue of Publication
12
ISSN
0893-228X
NIOSH Division
HELD
Source Name
Chemical Research in Toxicology
State
WV
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