Determination of plasma genistein fatty acid esters following administration of genistein or genistein 4'7-O-dioleate in monkeys

Maija Badeau, Matti J Tikkanen, Susan E Appt, Herman Adlercreutz, Thomas B Clarkson, Antti Hoikkala, Kristiina Wähälä, Tomi Sakari Mikkola

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    Soy-derived isoflavone phytoestrogens, such as genistein (4',5,7-trihydroxyisoflavone), have been shown to protect low-density lipoprotein from oxidation. In addition, human plasma was previously shown to be capable of converting genistein into lipophilic fatty acid esters that accumulate in lipoproteins in vitro. We developed a method for the quantitation of genistein fatty acid esters in plasma. Furthermore, the method was utilized to measure genistein ester concentrations in monkey plasma following administration of genistein or genistein 4',7-O-dioleate. After extraction from plasma, genistein fatty acid esters were separated from unesterified genistein by Sephadex LH-20 column chromatography. The genistein ester fraction was hydrolyzed by saponification and purified by a second chromatography on Sephadex LH-20. The hydrolyzed genistein esters were measured by time-resolved fluoroimmunoassay. Adult female rhesus monkeys (n = 10) received a subcutaneous injection of genistein (24 mg, n = 2) or genistein 4',7-O-dioleate (71 mg, n = 3) or an oral dose of genistein (24 mg, n = 2) or genistein 4',7-O-dioleate (71 mg, n = 3). Plasma was collected at 4, 8, and 24 h post-dosing. Following subcutaneous administration of genistein 4',7-O-dioleate, the plasma concentrations of genistein esters became elevated in two out of three monkeys with 8-h values exceeding 7.5 nmol/L and 24-h values above 12 nmol/L. Other treatments resulted in lower plasma values ranging between 2.7 and 6.1 nmol/L. The lower limit of detection for the method was 1.44 nmol/L. Subcutaneously administered genistein 4',7-O-dioleate was also converted to water-soluble conjugates, but oral administration did not elevate plasma genistein fatty acid ester levels. The results suggest that it may be possible to introduce intact genistein ester molecules into plasma by parenteral but not oral administration. (c) 2005 Elsevier B.V. All rights reserved.
    Originalspråkengelska
    TidskriftBiochimica and Biophysica Acta. Molecular and Cell Biology of Lipids
    Volym1738
    Sidor (från-till)115-120
    Antal sidor6
    ISSN1388-1981
    DOI
    StatusPublicerad - 2005
    MoE-publikationstypA1 Tidskriftsartikel-refererad

    Vetenskapsgrenar

    • 312 Klinisk medicin

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    @article{8f96852aec6a46b2af772959cb2a3275,
    title = "Determination of plasma genistein fatty acid esters following administration of genistein or genistein 4'7-O-dioleate in monkeys",
    abstract = "Soy-derived isoflavone phytoestrogens, such as genistein (4',5,7-trihydroxyisoflavone), have been shown to protect low-density lipoprotein from oxidation. In addition, human plasma was previously shown to be capable of converting genistein into lipophilic fatty acid esters that accumulate in lipoproteins in vitro. We developed a method for the quantitation of genistein fatty acid esters in plasma. Furthermore, the method was utilized to measure genistein ester concentrations in monkey plasma following administration of genistein or genistein 4',7-O-dioleate. After extraction from plasma, genistein fatty acid esters were separated from unesterified genistein by Sephadex LH-20 column chromatography. The genistein ester fraction was hydrolyzed by saponification and purified by a second chromatography on Sephadex LH-20. The hydrolyzed genistein esters were measured by time-resolved fluoroimmunoassay. Adult female rhesus monkeys (n = 10) received a subcutaneous injection of genistein (24 mg, n = 2) or genistein 4',7-O-dioleate (71 mg, n = 3) or an oral dose of genistein (24 mg, n = 2) or genistein 4',7-O-dioleate (71 mg, n = 3). Plasma was collected at 4, 8, and 24 h post-dosing. Following subcutaneous administration of genistein 4',7-O-dioleate, the plasma concentrations of genistein esters became elevated in two out of three monkeys with 8-h values exceeding 7.5 nmol/L and 24-h values above 12 nmol/L. Other treatments resulted in lower plasma values ranging between 2.7 and 6.1 nmol/L. The lower limit of detection for the method was 1.44 nmol/L. Subcutaneously administered genistein 4',7-O-dioleate was also converted to water-soluble conjugates, but oral administration did not elevate plasma genistein fatty acid ester levels. The results suggest that it may be possible to introduce intact genistein ester molecules into plasma by parenteral but not oral administration. (c) 2005 Elsevier B.V. All rights reserved.",
    keywords = "312 Clinical medicine",
    author = "Maija Badeau and Tikkanen, {Matti J} and Appt, {Susan E} and Herman Adlercreutz and Clarkson, {Thomas B} and Antti Hoikkala and Kristiina W{\"a}h{\"a}l{\"a} and Mikkola, {Tomi Sakari}",
    year = "2005",
    doi = "10.1016/j.bbalip.2005.10.005",
    language = "English",
    volume = "1738",
    pages = "115--120",
    journal = "Biochimica and Biophysica Acta. Molecular and Cell Biology of Lipids",
    issn = "1388-1981",
    publisher = "Elsevier Scientific Publ. Co",

    }

    TY - JOUR

    T1 - Determination of plasma genistein fatty acid esters following administration of genistein or genistein 4'7-O-dioleate in monkeys

    AU - Badeau, Maija

    AU - Tikkanen, Matti J

    AU - Appt, Susan E

    AU - Adlercreutz, Herman

    AU - Clarkson, Thomas B

    AU - Hoikkala, Antti

    AU - Wähälä, Kristiina

    AU - Mikkola, Tomi Sakari

    PY - 2005

    Y1 - 2005

    N2 - Soy-derived isoflavone phytoestrogens, such as genistein (4',5,7-trihydroxyisoflavone), have been shown to protect low-density lipoprotein from oxidation. In addition, human plasma was previously shown to be capable of converting genistein into lipophilic fatty acid esters that accumulate in lipoproteins in vitro. We developed a method for the quantitation of genistein fatty acid esters in plasma. Furthermore, the method was utilized to measure genistein ester concentrations in monkey plasma following administration of genistein or genistein 4',7-O-dioleate. After extraction from plasma, genistein fatty acid esters were separated from unesterified genistein by Sephadex LH-20 column chromatography. The genistein ester fraction was hydrolyzed by saponification and purified by a second chromatography on Sephadex LH-20. The hydrolyzed genistein esters were measured by time-resolved fluoroimmunoassay. Adult female rhesus monkeys (n = 10) received a subcutaneous injection of genistein (24 mg, n = 2) or genistein 4',7-O-dioleate (71 mg, n = 3) or an oral dose of genistein (24 mg, n = 2) or genistein 4',7-O-dioleate (71 mg, n = 3). Plasma was collected at 4, 8, and 24 h post-dosing. Following subcutaneous administration of genistein 4',7-O-dioleate, the plasma concentrations of genistein esters became elevated in two out of three monkeys with 8-h values exceeding 7.5 nmol/L and 24-h values above 12 nmol/L. Other treatments resulted in lower plasma values ranging between 2.7 and 6.1 nmol/L. The lower limit of detection for the method was 1.44 nmol/L. Subcutaneously administered genistein 4',7-O-dioleate was also converted to water-soluble conjugates, but oral administration did not elevate plasma genistein fatty acid ester levels. The results suggest that it may be possible to introduce intact genistein ester molecules into plasma by parenteral but not oral administration. (c) 2005 Elsevier B.V. All rights reserved.

    AB - Soy-derived isoflavone phytoestrogens, such as genistein (4',5,7-trihydroxyisoflavone), have been shown to protect low-density lipoprotein from oxidation. In addition, human plasma was previously shown to be capable of converting genistein into lipophilic fatty acid esters that accumulate in lipoproteins in vitro. We developed a method for the quantitation of genistein fatty acid esters in plasma. Furthermore, the method was utilized to measure genistein ester concentrations in monkey plasma following administration of genistein or genistein 4',7-O-dioleate. After extraction from plasma, genistein fatty acid esters were separated from unesterified genistein by Sephadex LH-20 column chromatography. The genistein ester fraction was hydrolyzed by saponification and purified by a second chromatography on Sephadex LH-20. The hydrolyzed genistein esters were measured by time-resolved fluoroimmunoassay. Adult female rhesus monkeys (n = 10) received a subcutaneous injection of genistein (24 mg, n = 2) or genistein 4',7-O-dioleate (71 mg, n = 3) or an oral dose of genistein (24 mg, n = 2) or genistein 4',7-O-dioleate (71 mg, n = 3). Plasma was collected at 4, 8, and 24 h post-dosing. Following subcutaneous administration of genistein 4',7-O-dioleate, the plasma concentrations of genistein esters became elevated in two out of three monkeys with 8-h values exceeding 7.5 nmol/L and 24-h values above 12 nmol/L. Other treatments resulted in lower plasma values ranging between 2.7 and 6.1 nmol/L. The lower limit of detection for the method was 1.44 nmol/L. Subcutaneously administered genistein 4',7-O-dioleate was also converted to water-soluble conjugates, but oral administration did not elevate plasma genistein fatty acid ester levels. The results suggest that it may be possible to introduce intact genistein ester molecules into plasma by parenteral but not oral administration. (c) 2005 Elsevier B.V. All rights reserved.

    KW - 312 Clinical medicine

    U2 - 10.1016/j.bbalip.2005.10.005

    DO - 10.1016/j.bbalip.2005.10.005

    M3 - Article

    VL - 1738

    SP - 115

    EP - 120

    JO - Biochimica and Biophysica Acta. Molecular and Cell Biology of Lipids

    JF - Biochimica and Biophysica Acta. Molecular and Cell Biology of Lipids

    SN - 1388-1981

    ER -