Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • 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
  • 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
    • 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
  • Visit dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
Research ArticleArticle

Effects of Bergamottin on Human and Monkey Drug-Metabolizing Enzymes in Primary Cultured Hepatocytes

Yuan Hua Wen, Jasminder Sahi, Ellen Urda, Shaila Kulkarni, Kelly Rose, Xianxian Zheng, Jacqueline F. Sinclair, Hongbo Cai, Stephen C. Strom and Vsevolod E. Kostrubsky
Drug Metabolism and Disposition September 2002, 30 (9) 977-984; DOI: https://doi.org/10.1124/dmd.30.9.977
Yuan Hua Wen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jasminder Sahi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ellen Urda
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shaila Kulkarni
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kelly Rose
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xianxian Zheng
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jacqueline F. Sinclair
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hongbo Cai
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stephen C. Strom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vsevolod E. Kostrubsky
  • 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
Loading

Abstract

We investigated the effect of bergamottin, a major furanocoumarin in grapefruit juice, on phase I and phase II drug-metabolizing enzymes using cultured human and monkey hepatocytes. Both cultured systems were compared and evaluated for the direct effects of bergamottin as well as control treatments on liver enzymes. Treatment of hepatocytes with 0.1, 1, 5, and 10 μM bergamottin resulted in a concentration-dependent reduction in CYP3A4 activity (40–100%) in both human and monkey cells, as measured by testosterone 6β-hydroxylase activity. Bergamottin was potent at eliciting these inhibitory effects at both basal and induced states of CYP3A. Bergamottin (5 μM) completely inhibited α-naphthoflavone-induced ethoxyresorufinO-dealkylase (EROD) and methoxyresorufinO-dealkylase (MROD) activities in human hepatocytes and caused a 100% decrease in EROD activity in monkey hepatocytes. A 48-h exposure of cultured human hepatocytes to bergamottin resulted in increased levels of immunoreactive CYP3A4, CYP1A1, and CYP1A2 proteins, and CYP3A4, CYP1A1, CYP1A2, CYP2B6, and UDP-glucuronosyl transferase mRNAs. There was only a 20 to 30% reduction in glucuronidation and sulfation of 4-methylumbelliferone in human hepatocytes by 10 μM bergamottin and no effect on conjugation in the monkey hepatocytes. These results suggest that bergamottin causes both inhibition of CYP3A and CYP1A1/2 enzymatic activities and induction of correspondent proteins and mRNAs.

Footnotes

  • This work was supported in part by Grants GM 61393, GM 60346, ESO 5780, and DK 92310 to Stephen C. Strom.

  • Abbreviations used are::
    AUC
    area under the curve
    P450
    cytochrome P-450
    4-MU
    4-methylumbelliferone
    SSC
    standard saline citrate
    TAO
    triacetyloleandomycin
    β-NF
    β-naphthoflavone
    HPLC
    high-performance liquid chromatography
    EROD
    ethoxyresorufin O-dealkylase
    MROD
    methoxyresorufinO-dealkylase
    DMSO
    dimethyl sulfoxide
    3MC
    3-methylcholanthrene
    • Received March 21, 2002.
    • Accepted May 29, 2002.
  • U.S. Government
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: 30 (9)
Drug Metabolism and Disposition
Vol. 30, Issue 9
1 Sep 2002
  • Table of Contents
  • About the Cover
  • Index by author
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.
Effects of Bergamottin on Human and Monkey Drug-Metabolizing Enzymes in Primary Cultured Hepatocytes
(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

Effects of Bergamottin on Human and Monkey Drug-Metabolizing Enzymes in Primary Cultured Hepatocytes

Yuan Hua Wen, Jasminder Sahi, Ellen Urda, Shaila Kulkarni, Kelly Rose, Xianxian Zheng, Jacqueline F. Sinclair, Hongbo Cai, Stephen C. Strom and Vsevolod E. Kostrubsky
Drug Metabolism and Disposition September 1, 2002, 30 (9) 977-984; DOI: https://doi.org/10.1124/dmd.30.9.977

Citation Manager Formats

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

Effects of Bergamottin on Human and Monkey Drug-Metabolizing Enzymes in Primary Cultured Hepatocytes

Yuan Hua Wen, Jasminder Sahi, Ellen Urda, Shaila Kulkarni, Kelly Rose, Xianxian Zheng, Jacqueline F. Sinclair, Hongbo Cai, Stephen C. Strom and Vsevolod E. Kostrubsky
Drug Metabolism and Disposition September 1, 2002, 30 (9) 977-984; DOI: https://doi.org/10.1124/dmd.30.9.977
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Humanized PXR-CAR-CYP3A4/7 Mouse as Model of Induction
  • Ozanimod Human Metabolism and Disposition
  • High-Throughput Characterization of SLCO1B1 VUS
Show more Article

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 © 2021 by the American Society for Pharmacology and Experimental Therapeutics