Abstract
Genistein is a natural phytoestrogen of the soybean, and bisphenol A (BPA) is a synthetic chemical used in the production of polycarbonate plastics. Both genistein and BPA disrupt the endocrine system in vivo and in vitro. Growing concerns of altered xenobiotic metabolism due to concomitant exposures from soy milk in BPA-laden baby bottles has warranted the investigation of the glucuronidation rate of genistein in the absence and presence (25 μM) of BPA by human liver microsomes (HLM) and rat liver microsomes (RLM). HLM yield Vmax values of 0.93 ± 0.10 nmol · min−1 · mg−1 and 0.62 ± 0.05 nmol · min−1 · mg−1 in the absence and presence of BPA, respectively. Km values for genistein glucuronidation by HLM in the absence and presence of BPA are 15.1 ± 7.9 μM and 21.5 ± 7.7 μM, respectively, resulting in a Ki value of 58.7 μM for BPA. Significantly reduced Vmax and unchanged Km in the presence of BPA in HLM are suggestive of noncompetitive inhibition. In RLM, the presence of BPA resulted in a Ki of 35.7 μM, an insignificant change in Vmax (2.91 ± 0.26 nmol · min−1 · mg−1 and 3.05 ± 0.41 nmol · min−1 · mg−1 in the absence and presence of BPA, respectively), and an increase in apparent Km (49.4 ± 14 μM with no BPA and 84.0 ± 28 μM with BPA), indicative of competitive inhibition. These findings are significant because they suggest that BPA is capable of inhibiting the glucuronidation of genistein in vitro, and that the type of inhibition is different between HLM and RLM.
Footnotes
This work was supported by the National Institutes of Health National Institute of Environmental Health Sciences [Grants T32-ES007148, ES05022]; and the Environmental and Occupational Health Sciences Institute.
Coughlin JL (2011) Characterization of the Inhibition of Genistein Glucuronidation by Bisphenol A in Human and Rat Liver Microsomes. Master's thesis, Rutgers University, Piscataway, New Jersey.
Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
↵ The online version of this article (available at http://dmd.aspetjournals.org) contains supplemental material.
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ABBREVIATIONS:
- UGT
- UDP-glucuronosyltransferase
- UDPGA
- UDP-glucuronic acid
- BPA
- bisphenol A
- HLM
- human liver microsomes
- RLM
- rat liver microsomes
- BPA gluc
- bisphenol A β-d-glucuronide
- genistein gluc
- genistein 4′-β-d-glucuronide
- HPLC
- high-performance liquid chromatography
- SPE
- solid-phase extraction
- MS/MS
- tandem mass spectrometry.
- Received August 15, 2011.
- Accepted December 6, 2011.
- Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics
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