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.
|Lehti||Biochimica and Biophysica Acta. Molecular and Cell Biology of Lipids|
|DOI - pysyväislinkit|
|Tila||Julkaistu - 2005|
|OKM-julkaisutyyppi||A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu|
- 312 Kliiniset lääketieteet