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

Effects of Typical Inducers on Olfactory Xenobiotic-Metabolizing Enzyme, Transporter, and Transcription Factor Expression in Rats

Nicolas Thiebaud, Maud Sigoillot, Joëlle Chevalier, Yves Artur, Jean-Marie Heydel and Anne-Marie Le Bon
Drug Metabolism and Disposition October 2010, 38 (10) 1865-1875; DOI: https://doi.org/10.1124/dmd.110.035014
Nicolas Thiebaud
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maud Sigoillot
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joëlle Chevalier
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yves Artur
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jean-Marie Heydel
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anne-Marie Le Bon
  • 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

Several xenobiotic-metabolizing enzymes (XMEs) have been identified in the olfactory mucosa (OM) of mammals. However, the molecular mechanisms underlying the regulation of these enzymes have been little explored. In particular, information on the expression of the transcriptional factors in this tissue is quite limited. The aim of the present study was to examine the impact of five typical inducers, Aroclor 1254, 3-methylcholanthrene, dexamethasone, phenobarbital, and ethoxyquin, on the activities and mRNA expression of several XMEs in the OM and in the liver of rats. We also evaluated the effects of these treatments on the mRNA expression of transcription factors and transporters. On the whole, the intensities of the effects were lower in the OM than in the liver. Dexamethasone was found to be the most efficient treatment in the OM. Dexamethasone induced the transcription of several olfactory phase I, II, and III genes [such as cytochromes P450 2A3 and 3A9, UDP-glucuronosyltransferase (UGT) 2A1, and multidrug resistance-related protein type 1] and increased UGT activities. We observed that dexamethasone up-regulated sulfotransferase 1C1 expression in the OM but down-regulated it in the liver. Aroclor and ethoxyquin induced the gene expression of CYP1A and quinone reductase, respectively, in the OM. The transcription factors aryl hydrocarbon receptor, nuclear factor E2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor α, pregnane X receptor, and glucocorticoid receptor were detected in the OM, but no constitutive androstane receptor expression was observed. Dexamethasone and Aroclor enhanced olfactory Nrf2 expression. These results demonstrate that olfactory XME can be modulated by chemicals and that the mechanisms involved in the regulation of these enzymes are tissue-specific.

Footnotes

  • This work was supported by the Agence Nationale de la Recherche [Grant ANR-05-PNRA-1.E7 Aromalim].

  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

    doi:10.1124/dmd.110.035014.

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

  • ABBREVIATIONS:

    XME
    xenobiotic-metabolizing enzymes
    OM
    olfactory mucosa
    P450
    cytochrome P450
    ALDH
    aldehyde dehydrogenase
    EPHX
    epoxide hydrolase
    UGT
    UDP glucuronosyltransferase
    SULT
    sulfotransferase
    GST
    glutathione S-transferase
    MDR
    multidrug resistance protein
    MRP
    multidrug resistance-associated protein
    OAT
    organic anion transporter
    OCT
    organic cation transporter
    AR
    Aroclor 1234
    AhR
    aryl hydrocarbon receptor
    CAR
    constitutive androstane receptor
    PXR
    pregnane X receptor
    Nrf2
    nuclear factor E2-related factor 2
    MC
    3-methylcholanthrene
    DEX
    dexamethasone
    O
    oil
    C
    control
    PB
    phenobarbital
    EQ
    ethoxyquin
    RT-PCR
    reverse transcriptase-quantitative polymerase chain reaction
    POD
    phenacetin-O-deethylase
    NO
    nifedipine oxidase
    CZX
    chlorzoxazone hydroxylase
    HPLC
    high-performance liquid chromatography
    EROD
    ethoxyresorufin-O-deethylase
    PROD
    pentoxyresorufin-O-dealkylase
    NQO1
    quinone reductase
    mGST
    glutathione S-transferase
    4-MU
    4-methylumbelliferone
    AOH3
    aldehyde oxidase homolog 3
    PNP
    p-nitrophenol
    PPAR
    peroxisome proliferator-activated receptor
    GR
    glucocorticoid receptor.

  • Received June 18, 2010.
  • Accepted July 16, 2010.
  • Copyright © 2010 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: 38 (10)
Drug Metabolism and Disposition
Vol. 38, Issue 10
1 Oct 2010
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • 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.
Effects of Typical Inducers on Olfactory Xenobiotic-Metabolizing Enzyme, Transporter, and Transcription Factor Expression in Rats
(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 Typical Inducers on Olfactory Xenobiotic-Metabolizing Enzyme, Transporter, and Transcription Factor Expression in Rats

Nicolas Thiebaud, Maud Sigoillot, Joëlle Chevalier, Yves Artur, Jean-Marie Heydel and Anne-Marie Le Bon
Drug Metabolism and Disposition October 1, 2010, 38 (10) 1865-1875; DOI: https://doi.org/10.1124/dmd.110.035014

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 Typical Inducers on Olfactory Xenobiotic-Metabolizing Enzyme, Transporter, and Transcription Factor Expression in Rats

Nicolas Thiebaud, Maud Sigoillot, Joëlle Chevalier, Yves Artur, Jean-Marie Heydel and Anne-Marie Le Bon
Drug Metabolism and Disposition October 1, 2010, 38 (10) 1865-1875; DOI: https://doi.org/10.1124/dmd.110.035014
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

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

Related Articles

Cited By...

More in this TOC Section

  • Functional Characterization of 29 CYP4F2 Variants
  • Exposure-toxicity relation of apatinib
  • ABC phenomenon potentiates anti-HCC efficacy
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 © 2023 by the American Society for Pharmacology and Experimental Therapeutics