Pharmacokinetics of [C-14]Genistein in the rat: Gender-related differences, potential mechanisms of biological action, and implications for human health

Mass balance, plasma pharmacokinetics, tissue distribution, and metabolism of [C-14]genistein were investigated in male and female rats (n = 5) follow ing an oral dose of [C-14]genistein (4 mg kg(-1)) to determine potential si tes and mechanisms of biological action. Mean total excretion of radioactiv ity in urine and feces for both sexes was 66 and 33% of the dose respective ly at 166 h after administration. Mean and maximal concentrations of radioa ctivity in plasma were significantly (p < 0.02) higher in male than female rats, with half-lives of 12.4 and 8.5 h, respectively. The concentration of radioactivity was significantly (p < 0.002) higher in liver from females t han males and in reproductive (vagina, uterus, ovary, and prostate) compare d with other peripheral organs. Analysis of plasma extracts by radio-HPLC-M S indicated that the predominant metabolites were genistein glucuronides, 4 -hydroxyphenyl-2-propionic acid, and trace amounts of parent compound (<5%) . Radioactive residues in uterus and prostate were predominantly parent com pound and 4-hydroxyphenyl-2-propionic acid, respectively. Significantly (p < 0.05) increased retention of [C-14]genistein or metabolites was associate d with reproductive organs, such as vagina, uterus, ovary, and prostate, li kely to contain relatively high concentrations of estrogen receptors or bin ding proteins compared with other peripheral tissues. Factors liable to inf luence bioavailability of biologically active genistein or metabolites, suc h as dietary intake, warrant further investigation to determine the risks o r benefits for different consumer groups of phytoestrogen-containing foods. (C) 2000 Academic Press.