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  • Hepatic processing determines dual activity of α-tocopheryl succinate: a novel paradigm for a shift in biological activity due to pro-vitamin-to-vitamin conversion

    Author(s)
    Neuzil, J
    Massa, H
    Griffith University Author(s)
    Neuzil, Jiri
    Massa, Helen M.
    Year published
    2005
    Metadata
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    Abstract
    Redox-silent vitamin E analogues, represented by a-tocopheryl succinate, are potent anti-cancer drugs with potential secondary bioactivity due to their processing in vivo. Here we verified the hypothesis that hepatic processing of these agents determines the secondary effect. Mice were repeatedly injected with a-tocopheryl succinate, and their systemic and hepatic vein blood was assessed for a-tocopheryl succinate and its hydrolysis product, vitamin E (a-tocopherol). While levels of a-tocopherol doubled compared to control mice and a-tocopheryl succinate accumulated in the systemic blood, no a-tocopheryl succinate was detected ...
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    Redox-silent vitamin E analogues, represented by a-tocopheryl succinate, are potent anti-cancer drugs with potential secondary bioactivity due to their processing in vivo. Here we verified the hypothesis that hepatic processing of these agents determines the secondary effect. Mice were repeatedly injected with a-tocopheryl succinate, and their systemic and hepatic vein blood was assessed for a-tocopheryl succinate and its hydrolysis product, vitamin E (a-tocopherol). While levels of a-tocopherol doubled compared to control mice and a-tocopheryl succinate accumulated in the systemic blood, no a-tocopheryl succinate was detected in blood draining the liver. We conclude that hepatic processing endows compounds like a-tocopheryl succinate with a secondary, anti-oxidant/anti-inflammatory activity due to converting it to the redox-active a-tocopherol. Our finding epitomises a novel, general paradigm, according to which a drug can be converted in the liver into a product that has a different beneficial bioactivity.
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    Journal Title
    Biochemical and biophysical research communications
    Volume
    327
    Publisher URI
    http://www.sciencedirect.com/science/journal/0006291X
    DOI
    https://doi.org/10.1016/j.bbrc.2004.12.115
    Copyright Statement
    © 2005 Elsevier : Reproduced in accordance with the copyright policy of the publisher : This journal is available online - use hypertext links.
    Subject
    Medicinal and biomolecular chemistry
    Biochemistry and cell biology
    Medical biochemistry and metabolomics
    Publication URI
    http://hdl.handle.net/10072/4745
    Collection
    • Journal articles

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