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dc.contributor.advisorLiebler, Daniel C.en_US
dc.contributor.authorKramer-Stickland, Kimberly Ann, 1970-en_US
dc.creatorKramer-Stickland, Kimberly Ann, 1970-en_US
dc.date.accessioned2013-05-09T09:07:06Z
dc.date.available2013-05-09T09:07:06Z
dc.date.issued1998en_US
dc.identifier.urihttp://hdl.handle.net/10150/288782
dc.description.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.
dc.language.isoen_USen_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.subjectHealth Sciences, Toxicology.en_US
dc.subjectHealth Sciences, Pharmacology.en_US
dc.subjectChemistry, Biochemistry.en_US
dc.titleFate of vitamin E in UVB-irradiated mouse skin and in vitro systems: Antioxidant and photochemistryen_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
thesis.degree.grantorUniversity of Arizonaen_US
thesis.degree.leveldoctoralen_US
dc.identifier.proquest9817362en_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplinePharmacology and Toxicologyen_US
thesis.degree.namePh.D.en_US
dc.identifier.bibrecord.b38269946en_US
refterms.dateFOA2018-09-06T05:00:42Z
html.description.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.


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