Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Drug Metabolism & Disposition
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Drug Metabolism & Disposition

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
Research ArticleArticle

Inhibition of Genistein Glucuronidation by Bisphenol A in Human and Rat Liver Microsomes

Janis L. Coughlin, Paul E. Thomas and Brian Buckley
Drug Metabolism and Disposition March 2012, 40 (3) 481-485; DOI: https://doi.org/10.1124/dmd.111.042366
Janis L. Coughlin
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Paul E. Thomas
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Brian Buckley
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF
Loading

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.

    http://dx.doi.org/10.1124/dmd.111.042366.

  • ↵Embedded Image The online version of this article (available at http://dmd.aspetjournals.org) contains supplemental material.

  • 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
View Full Text

 

DMD articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Drug Metabolism and Disposition: 40 (3)
Drug Metabolism and Disposition
Vol. 40, Issue 3
1 Mar 2012
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Drug Metabolism & Disposition article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Inhibition of Genistein Glucuronidation by Bisphenol A in Human and Rat Liver Microsomes
(Your Name) has forwarded a page to you from Drug Metabolism & Disposition
(Your Name) thought you would be interested in this article in Drug Metabolism & Disposition.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

INHIBITION OF GENISTEIN GLUCURONIDATION IN HLM AND RLM

Janis L. Coughlin, Paul E. Thomas and Brian Buckley
Drug Metabolism and Disposition March 1, 2012, 40 (3) 481-485; DOI: https://doi.org/10.1124/dmd.111.042366

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleArticle

INHIBITION OF GENISTEIN GLUCURONIDATION IN HLM AND RLM

Janis L. Coughlin, Paul E. Thomas and Brian Buckley
Drug Metabolism and Disposition March 1, 2012, 40 (3) 481-485; DOI: https://doi.org/10.1124/dmd.111.042366
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Authorship Contributions
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Human ADME Properties of Abrocitinib
  • MSCs Pharmacokinetics under liver diseases
  • In Vitro-In Vivo Extrapolation Using Empirical Scaling
Show more Articles

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About DMD
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Journal of Pharmacology and Experimental Therapeutics
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-009X (Online)

Copyright © 2022 by the American Society for Pharmacology and Experimental Therapeutics