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Topical application of lotions containing the phytoestrogenic isoflavonoid equol have been reported to protect mice against UV radiation-induced inflammation, immune suppression and photocarcinogenesis. The photoimmune protective property was shown to depend on equol's activation of oestrogen receptor signalling in the skin. However, isoflavones are also recognised for their antioxidant properties in biological systems. As endogenous cutaneous antioxidant enzymes including the inducible stress protein haem oxygenase (HO)-1, have photoprotective efficacy, this study in the Skh:hr-1 hairless mouse seeks evidence for an antioxidant role for equol in contributing to its photoimmune protection. Oxidative stress has been measured as UVA-induced lipid peroxidation in the mouse skin, and was dose-dependently inhibited by topical equol. Inhibition of the UVA (320–400 nm)-inducible HO activity significantly reduced the level of equol protection against lipid peroxidation, thereby attributing a component of equol's lipid protection capacity to this stress enzyme. It was consistent that topical equol enhanced the level of HO induction by UVA irradiation in both skin and liver. Subsequently, the dose-dependent protection by topical equol lotions against solar simulated UV radiation induced immunosuppression, measured by the contact hypersensitivity reaction, was found also to be partially reduced by the inhibition of HO activity. Therefore, in addition to the activation by equol of oestrogenic signalling pathways for photoprotection, this isoflavonoid also provides UV-protective antioxidant effects that depend partially on HO-1 induction. [ABSTRACT FROM AUTHOR]

The phytoestrogenic isoflavonoid equol is known to protect against solar-simulated UV radiation-induced inflammation, immunosuppression, and skin carcinogenesis. The mechanism may involve antioxidant actions, because equol not only is a radical scavenger but also enhances the induction of a relevant cutaneous antioxidant, metallothionein. However, this study in female hairless mice examined whether the estrogenicity of the isoflavonoid might be responsible. Protection by topically applied equol against photoimmune suppression was found to be strongly and dose-dependently inhibited by the estrogen receptor (ER) antagonist ICI 182,780. Furthermore, ICI 182,780 alone was found to significantly exacerbate immunosuppression resulting from solar-simulated UV radiation irradiation, suggesting a natural role for the ER in photoimmune protection. In support of this role, topical application of the physiological ligand 17-β-estradiol also provided dose-dependent photoimmune protection, inhibitable by ICI 182,780, that was attributed largely to the inactivation of the downstream actions of cis-urocanic acid, an important endogenous immunosuppressive photoproduct. Thus, a hitherto unrecognized function of the ER as a normal photoprotective immune regulator in the skin was revealed. The relationship between equol and cutaneous metallothionein suggests an association of the ER with this inducible antioxidant in constraining the photoimmune-suppressed state and therefore in the prevention of the facilitation of photo-carcinogenesis by this immunological defect. This role for the ER may underlie important gender-specific differences in UV-responsiveness that would reflect different needs for environmental photoprotection in males and females. [ABSTRACT FROM AUTHOR]