Fate of vitamin E in UVB-irradiated mouse skin and in vitro systems: Antioxidant and photochemistry
AdvisorLiebler, Daniel C.
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PublisherThe University of Arizona.
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AbstractPhotochemical and antioxidant reactions of α-tocopherol (α-TH, vitamin E) were studied by monitoring the fate of α-TH in UVB irradiated liposomes, solution, and mouse skin. α-TH was rapidly depleted in UVB irradiated mouse skin and in vitro systems. Oxidative damage, assessed by monitoring lipid peroxidation, was suppressed in UVH-irradiated liposomes until α-TH was depleted to 20% of initial levels. In all three systems, products previously identified as marker products for peroxyl radical scavenging by α-TH were observed, including α-tocopherolquinone (α-TQ), α-tocopherolquinone 2,3-epoxide (α-TQE 1), α-tocopherolquinone 5,6-epoxide (α-TQE 2) and several 8a-(hydroperoxy) epoxytocopherones. In addition, a product resulting from photochemical consumption of α-tocopherol, a spirodimer, was identified by HPLC and HPLC-MS. These studies provide the first evidence of the fate of vitamin E in UVB irradiated in vitro and in vivo systems. We have also assessed the hydrolysis of the vitamin E ester α-tocopherol acetate (α-TAc) to the active antioxidant α-TH in mouse epidermis and in supernatant from epidermal homogenates. Topically administered α-tocopherol prevents UVB photocarcinogenesis in C3W mice, whereas α-tocopherol acetate does not. Hydrolysis in skin was monitored in mice treated topically with deuterium labeled α-TAc (d₃-α-TAc). α-TAc was hydrolyzed to α-TH in mouse skin, and this effect was enhanced by prior UVB treatment. We hypothesized that prior UVB exposure may increase hydrolysis of α-TAc by increasing epidermal esterase activity. Non specific esterase (NSE) activity was measured in the 2000 x g supernatant from epidermis of unirradiated and irradiated mice. α-Napthyl acetate (α-NA), a NSE substrate, was converted to α-napthol (α-NOH) in supernatants from unirradiated mice. Hydrolysis of α-TAc to α-TH also occurred in supernatant from unirradiated mice, and hydrolysis of both α-NA and α-TH was enhanced in supernatants from UVB-irradiated mice. These data indicate that NSE activity was increased by UVB in the skin, that α-TAc is converted to α-TH in the homogenate fraction containing NSE, and that UVB exposure modulates the metabolism of α-TAc to α-TH in vivo.
Degree ProgramGraduate College
Pharmacology and Toxicology