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

Induction of Cytochrome P450 Enzymes in Cultured Precision-Cut Human Liver Slices

Robert J. Edwards, Roger J. Price, Patricia S. Watts, Anthony B. Renwick, J. Michael Tredger, Alan R. Boobis and Brian G. Lake
Drug Metabolism and Disposition March 2003, 31 (3) 282-288; DOI: https://doi.org/10.1124/dmd.31.3.282
Robert J. Edwards
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Roger J. Price
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Patricia S. Watts
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anthony B. Renwick
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
J. Michael Tredger
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alan R. Boobis
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Brian G. Lake
  • 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

Precision-cut human liver slices obtained from 11 donors were cultured for 72 h in a defined medium (serum free Williams' medium E) supplemented with 0.1 μM insulin and 0.1 μM dexamethasone (DEX). Liver slices were treated with 50 μM concentrations of β -naphthoflavone (BNF), lansoprazole, rifampicin (RIF), DEX and methylclofenapate and 500 μM sodium phenobarbital (NaPB). The relative apoprotein levels of 12 cytochrome P450 (P450) enzymes were determined in liver slice microsomes using a panel of antipeptide antibodies. Treatment with BNF significantly induced mean levels of CYP1A2 apoprotein to 160% of levels in 72-h control (no test compound) human liver slice microsomes. NaPB significantly induced levels of CYP3A4 apoprotein to 255% of control and RIF significantly induced levels of CYP2C19 and CYP3A4 apoproteins to 265 and 330% of control, respectively. In addition, treatment with RIF increased levels of CYP2A6 apoprotein to 205% of control, and treatment with both NaPB and RIF increased levels of CYP2B6 apoprotein to 370 and 615% of control, respectively. However, these increases were not statistically significant, owing to a variable response between liver slice preparations from different subjects, this being apparent for all inducible P450s. In contrast, none of the compounds examined significantly increased levels of CYP2C8, CYP2C9, CYP2D6, CYP2E1, and CYP4A11 apoproteins. Levels of CYP1A1 apoprotein were not detected in any liver slice sample, either before or after treatment with the model inducers. Overall, these results demonstrate the utility of cultured human liver slices for assessing the effects of chemicals on P450 enzymes.

Footnotes

  • We gratefully acknowledge the provision of financial support by a grant from the Commission of the European Communities (Project “Eurocyp”, BIOMED Contract No. BMH4-CT96-0254) and a Realizing Our Potential Award from the Medical Research Council.

  • Abbreviations used are::
    P450
    cytochrome P450
    BNF
    β-naphthoflavone
    RIF
    rifampicin
    DEX
    dexamethasone
    LANS
    lansoprazole
    MCP
    methylclofenapate
    NaPB
    sodium phenobarbital
    DMSO
    dimethyl sulfoxide
    • Received August 26, 2002.
    • Accepted November 26, 2002.
  • 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: 31 (3)
Drug Metabolism and Disposition
Vol. 31, Issue 3
1 Mar 2003
  • 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.
Induction of Cytochrome P450 Enzymes in Cultured Precision-Cut Human Liver Slices
(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

Induction of Cytochrome P450 Enzymes in Cultured Precision-Cut Human Liver Slices

Robert J. Edwards, Roger J. Price, Patricia S. Watts, Anthony B. Renwick, J. Michael Tredger, Alan R. Boobis and Brian G. Lake
Drug Metabolism and Disposition March 1, 2003, 31 (3) 282-288; DOI: https://doi.org/10.1124/dmd.31.3.282

Citation Manager Formats

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

Share
Research ArticleArticle

Induction of Cytochrome P450 Enzymes in Cultured Precision-Cut Human Liver Slices

Robert J. Edwards, Roger J. Price, Patricia S. Watts, Anthony B. Renwick, J. Michael Tredger, Alan R. Boobis and Brian G. Lake
Drug Metabolism and Disposition March 1, 2003, 31 (3) 282-288; DOI: https://doi.org/10.1124/dmd.31.3.282
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
    • Materials and Methods
    • Results
    • Discussion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Identification of payload-containing catabolites of ADCs
  • PK Interactions of Licorice with Cytochrome P450s
  • Biotransformation of Trastuzumab and Pertuzumab
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 © 2023 by the American Society for Pharmacology and Experimental Therapeutics