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    Antioxidant functions of beta-carotene

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    Author
    Kennedy, Todd Allen
    Issue Date
    1991
    Keywords
    Dissertations, Academic
    Antioxidants
    Beta carotene
    Pharmacology.
    Advisor
    Liebler, Daniel
    
    Metadata
    Show full item record
    Publisher
    The University of Arizona.
    Rights
    Copyright © 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.
    Abstract
    The provitamin A carotenoid β-carotene is an attractive candidate for the prevention of cancer. Indeed, abundant evidence suggests that β-carotene inhibits carcinogenesis. β-Carotene is thought to inhibit carcinogenesis by scavenging free radicals involved in tumor formation. However, there is no direct evidence that β-carotene traps radicals under conditions where it inhibits carcinogenesis. The overall objective of this dissertation research was to identify β-carotene oxidation products from β-carotene antioxidant reactions in model systems. Identification of such products will enable the direct measurement of β-carotene antioxidant activity in systems where it inhibits neoplastic transformation. In hexane solution, β-carotene was oxidized by peroxyl radicals to 5,6-epoxy-β, β-carotene, 15,15'-epoxy-β, β-carotene, a previously unreported product, and several unidentified polar products. Studies on the kinetics of product formation suggested that polar products are formed by both epoxide-dependent and -independent pathways. Because β-carotene may be localized within lipid bilayers in vivo, peroxyl radical oxidation of β-carotene in model membranes was examined. In soy phosphatidylcholine liposomes, β-carotene was oxidized by peroxyl radicals to the 5,6-epoxide and to unidentified polar products. β-Carotene antioxidant activity in the liposome system was the same at 15 torr and 160 torr O₂ and decreased at 760 torr O₂. These results suggest that β-carotene provides equal antioxidant protection in all tissues in vivo. The relative rates of product formation and β-carotene oxidation at different pO₂ suggested that β-carotene antioxidant activity is governed by the relative proportions of β-carotene radical trapping and autoxidation reactions, which do not contribute to radical trapping. Therefore, the loss of β-carotene antioxidant action at 760 torr O₂ may result from an increase in β-carotene oxidation by autoxidation pathways. The 5,6-epoxide was formed during both antioxidant reactions and autoxidation reactions and may be marker for the peroxyl radical oxidation of β-carotene. Attempts to study β-carotene antioxidant reactions in biological membranes were only partially successful. In vitro incorporation of β-carotene into microsomes was attempted by several methods. However, these efforts resulted in only modest β-carotene antioxidant activity in microsomes. These studies provide a basic understanding of β-carotene antioxidant chemistry in model systems. Their results will enable further investigation of β-carotene antioxidant action in biological systems.
    Type
    text
    Dissertation-Reproduction (electronic)
    Degree Name
    Ph.D.
    Degree Level
    doctoral
    Degree Program
    Pharmacology & Toxicology
    Graduate College
    Degree Grantor
    University of Arizona
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    Dissertations

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