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T05020: Absorption, distribution, metabolism and excretion of ¹⁴ C labelled genistein

Wednesday 14 July 2004

This research project aims to determine the fate of phytoestrogens (specifically genistein, an isoflavone) within the body and whether this differs in males and females.

• Study Duration
• Contractor
• Background
• Research Approach
• Results and findings
• Dissemination information
• Contact

Study Duration : January 1998 to July 2000

Contractor : Veterinary Laboratories Agency

Background

This project aims to determine the fate of phytoestrogens within the body and whether this differs in males and females. The type of phytoestrogen analysed will be the isoflavone genistein.

Research Approach

Labelled ( ¹⁴ C) genistein will be used to examine the tissue distribution, blood concentration and excretion of genistein and its metabolites in an experimental rat system.

Results and findings

In an experimental rat system, genistein and its metabolites mainly accumulated in the uterus, vagina, ovary, liver and prostate. The levels of genistein and its metabolites detected were sufficiently high to suggest that they could possibly induce biological effects by interacting with oestrogen receptors found in these tissues. How these findings relate to humans is, however, not known.

Several differences in the accumulation, blood concentration and excretion of genistein and its metabolites in males and females were identified:

• In females, genistein was the major residue in the uterus, ovary, vagina and liver. However, in males, the metabolite 4-hydroxyphenyl-2-propionic acid (HPPA) predominated in the prostate, whereas genistein glucuronide was the most abundant residue in the liver.
• The concentration of genistein and its metabolites in the blood was much lower in females. This may have been due to greater retention by the liver and/or more rapid elimination in females than males.
• In both males and females, genistein was excreted in urine (67%) and faeces (33%), mainly as metabolites. The major metabolite in males was HPPA, whereas in females the excreted residues were mainly conjugated metabolites of genistein.

However, the biological significance of these gender differences remains to be determined.

The results of this project were evaluated by the Committee on Toxicity (COT) as part of its review on phytoestrogens and health .

Dissemination information

Final report is available from the FSA Library and Information centre.
To obtain a copy, please contact the Enquiry Desk, Dr Elsie Widdowson Library and Information Services, Food Standards Agency tel: 020 7276 8181/8182 or email: library&info@foodstandards.gsi.gov.uk .

Publications

Coldham, N.G., Zhang, A.Q., Key, P., Sauer, M.J. (2002). Absolute bioavailability of [14C] genistein in the rat; plasma pharmacokinetics of parent compound, genistein glucuronide and total radioactivity. Eur J Drug Metab Pharmacokinet 27,249-58.

Coldham, N.G., Darby, C., Hows, M., King, L.J., Zhang, A.Q., and Sauer, M.J. (2002). Comparative metabolism of genistin by human and rat gut microflora: detection and identification of the end-products of metabolism. Xenobiotica 32, 45-62.

Coldham, N.G., Sauer, M.J. (2000). Pharmacokinetics of [(14)C]Genistein in the rat: gender-related differences, potential mechanisms of biological action, and implications for human health. Toxicol Appl Pharmacol. 164, 206-15.

Coldham, N.G., Howells, L.C., Santi, A., Montesissa, C., Langlais, C., King, L.J., Macpherson, D.D., Sauer, M.J. (1999). Biotransformation of genistein in the rat: elucidation of metabolite structure by product ion mass fragmentology. J Steroid Biochem Mol Biol 70, 169-84.

Contact : For any enquiries concerning this research project, please contact the relevant Programme contact or email: science@foodstandards.gsi.gov.uk

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