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
Rapid CommunicationShort Communication

Essential Role of the Cytochrome P450 Enzyme CYP2A5 in Olfactory Mucosal Toxicity of Naphthalene

Jinping Hu, Li Sheng, Lei Li, Xin Zhou, Fang Xie, Jaime D’Agostino, Yan Li and Xinxin Ding
Drug Metabolism and Disposition January 2014, 42 (1) 23-27; DOI: https://doi.org/10.1124/dmd.113.054429
Jinping Hu
Wadsworth Center, New York State Department of Health, and School of Public Health, State University of New York at Albany, Albany, New York (J.H., L.S., L.L., X.Z., F.X., J.D., X.D.); and Institute of Materia Medica, Chinese Academy of Medical Sciences & Perking Union Medical College, Beijing, China (J.H., L.S., Y.L.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Li Sheng
Wadsworth Center, New York State Department of Health, and School of Public Health, State University of New York at Albany, Albany, New York (J.H., L.S., L.L., X.Z., F.X., J.D., X.D.); and Institute of Materia Medica, Chinese Academy of Medical Sciences & Perking Union Medical College, Beijing, China (J.H., L.S., Y.L.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lei Li
Wadsworth Center, New York State Department of Health, and School of Public Health, State University of New York at Albany, Albany, New York (J.H., L.S., L.L., X.Z., F.X., J.D., X.D.); and Institute of Materia Medica, Chinese Academy of Medical Sciences & Perking Union Medical College, Beijing, China (J.H., L.S., Y.L.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xin Zhou
Wadsworth Center, New York State Department of Health, and School of Public Health, State University of New York at Albany, Albany, New York (J.H., L.S., L.L., X.Z., F.X., J.D., X.D.); and Institute of Materia Medica, Chinese Academy of Medical Sciences & Perking Union Medical College, Beijing, China (J.H., L.S., Y.L.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Fang Xie
Wadsworth Center, New York State Department of Health, and School of Public Health, State University of New York at Albany, Albany, New York (J.H., L.S., L.L., X.Z., F.X., J.D., X.D.); and Institute of Materia Medica, Chinese Academy of Medical Sciences & Perking Union Medical College, Beijing, China (J.H., L.S., Y.L.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jaime D’Agostino
Wadsworth Center, New York State Department of Health, and School of Public Health, State University of New York at Albany, Albany, New York (J.H., L.S., L.L., X.Z., F.X., J.D., X.D.); and Institute of Materia Medica, Chinese Academy of Medical Sciences & Perking Union Medical College, Beijing, China (J.H., L.S., Y.L.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yan Li
Wadsworth Center, New York State Department of Health, and School of Public Health, State University of New York at Albany, Albany, New York (J.H., L.S., L.L., X.Z., F.X., J.D., X.D.); and Institute of Materia Medica, Chinese Academy of Medical Sciences & Perking Union Medical College, Beijing, China (J.H., L.S., Y.L.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xinxin Ding
Wadsworth Center, New York State Department of Health, and School of Public Health, State University of New York at Albany, Albany, New York (J.H., L.S., L.L., X.Z., F.X., J.D., X.D.); and Institute of Materia Medica, Chinese Academy of Medical Sciences & Perking Union Medical College, Beijing, China (J.H., L.S., Y.L.)
  • 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

Naphthalene (NA), a ubiquitous environmental pollutant that can cause pulmonary and nasal toxicity in laboratory animals, requires cytochrome P450 (P450)–mediated metabolic activation to cause toxicity. Our recent study using a Cyp2f2-null mouse showed that CYP2F2 plays an essential role in NA-induced lung toxicity, but not in NA-induced nasal toxicity. The aim of this study was to determine whether mouse CYP2A5, abundantly expressed in nasal olfactory mucosa (OM) and the liver, but less in the lung, plays a major role in the bioactivation and toxicity of NA in the OM. We found, by comparing Cyp2a5-null and wild-type (WT) mice, that the loss of CYP2A5 expression led to substantial decreases in rates of NA metabolic activation by OM microsomes. The loss of CYP2A5 did not cause changes in systemic clearance of NA (at 200 mg/kg, i.p.). However, the Cyp2a5-null mice were much more resistant than were WT mice to NA-induced nasal toxicity (although not lung toxicity), when examined at 24 hours after NA dosing (at 200 mg/kg, i.p.), or to NA-induced depletion of total nonprotein sulfhydryl in the OM (although not in the lung), examined at 2 hours after dosing. Thus, mouse CYP2A5 plays an essential role in the bioactivation and toxicity of NA in the OM, but not in the lung. Our findings further illustrate the tissue-specific nature of the role of individual P450 enzymes in xenobiotic toxicity, and provide the basis for a more reliable assessment of the potential risks of NA nasal toxicity in humans.

Footnotes

    • Received August 22, 2013.
    • Accepted October 2, 2013.
  • This study was supported in part by the National Institutes of Health National Institute of Environmental Health Sciences [Grants ES007462 and ES020867].

  • dx.doi.org/10.1124/dmd.113.054429.

  • ↵Embedded ImageThis article has supplemental material available at dmd.aspetjournals.org.

  • Copyright © 2013 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: 42 (1)
Drug Metabolism and Disposition
Vol. 42, Issue 1
1 Jan 2014
  • 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.
Essential Role of the Cytochrome P450 Enzyme CYP2A5 in Olfactory Mucosal Toxicity of Naphthalene
(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
Rapid CommunicationShort Communication

Role of CYP2A5 in Naphthalene Nasal Toxicity

Jinping Hu, Li Sheng, Lei Li, Xin Zhou, Fang Xie, Jaime D’Agostino, Yan Li and Xinxin Ding
Drug Metabolism and Disposition January 1, 2014, 42 (1) 23-27; DOI: https://doi.org/10.1124/dmd.113.054429

Citation Manager Formats

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

Share
Rapid CommunicationShort Communication

Role of CYP2A5 in Naphthalene Nasal Toxicity

Jinping Hu, Li Sheng, Lei Li, Xin Zhou, Fang Xie, Jaime D’Agostino, Yan Li and Xinxin Ding
Drug Metabolism and Disposition January 1, 2014, 42 (1) 23-27; DOI: https://doi.org/10.1124/dmd.113.054429
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 and Discussion
    • Summary
    • Acknowledgments
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Preincubation Effects on Inhibition of OCT1 by CsA
  • Carbamazepine Metabolite and Hypersensitivity Reactions
  • SULT4A1 Preserves Mitochondrial Function
Show more Short Communications

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