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Peroxidase/H2O2 enhances hypersensitivity responses induced by eugenol: inhibitory effect of an antioxidant, lipoic acid.
Shvedova AA; Osipov AN; Jeffries BA; Kommineni C; Vallyathan V; Castranova V; Kagan VE
Environ Nutr Interact 1999; 3:15-31
Phenolic haptens are metabolically activated via phenoxyl radicals to produce highly reactive quinone methides, which are able to conjugate with macromolecules of antigen-presenting cells (APC) to initiate sensitization. We hypothesized that reduction of phenoxyl radicals to their phenolic forms by antioxidants should inhibit/attenuate formation of quinone methides and cause a delay/weakening of the immune response. This effect should depend on the antioxidant/pro-oxidant status of the APC. We used eugenol (4-allyl-2-methoxyphenol, EU), a phenolic compound that was readily oxidized to its quinone methide in the model system of horseradish peroxidase/H2O2 (HRP/H2O2). Oxidation of EU by HRP/H2O2 was effectively inhibited by ascorbate. While dihydrolipoic acid (DHLA) alone was not able to inhibit the EU oxidation, DHLA interacted synergistically with ascorbate, preventing HRP/H2O2-catalyzed oxidation of EU. Two murine models (24 BALB/c mice) were employed in this study to test whether oxidation of EU affects hypersensitivity response to the hapten. In the first model, mice were sensitized with oxidized (by HRP/H2O2) or nonoxidized EU. In mice sensitized with oxidized EU, challenge with hapten resulted in apparent edema, subacute inflammatory infiltrate, and ulcers in the epidermis. The inflammatory response to nonoxidized EU was less pronounced than that produced by oxidized EU. In the second model, mice were treated with an antioxidant, lipoic acid (LA), and sensitized with hapten. LA resulted in significant protection against EU-induced inflammatory response. From these results we conclude that antioxidant/pro-oxidant status in skin is important in dermal responses to oxidizable phenolic haptens, and anti-oxidants may be used for modulation of hypersensitivity responses.
Hypersensitivity; Antioxidants; Antioxidation; Phenolic-compounds; Phenols; Sensitization; Immune-reaction; Laboratory-animals; Animals; Animal-studies
Dr. A.A. Shvedova, Health Effects Laboratory Division, Pathology and Physiology Research Branch, NIOSH, 1095 Willowdale Road, Morgantown, WV 26505, USA
Environmental and Nutritional Interactions
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