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

Induction of Hepatic CYP2E1 by a Subtoxic Dose of Acetaminophen in Rats: Increase in Dichloromethane Metabolism and Carboxyhemoglobin Elevation

Su N. Kim, Ji Y. Seo, Da W. Jung, Min Y. Lee, Young S. Jung and Young C. Kim
Drug Metabolism and Disposition October 2007, 35 (10) 1754-1758; DOI: https://doi.org/10.1124/dmd.107.015545
Su N. Kim
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ji Y. Seo
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Da W. Jung
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Min Y. Lee
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Young S. Jung
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Young C. Kim
  • 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

Dichloromethane (DCM) is metabolically converted to carbon monoxide mostly by CYP2E1 in liver, resulting in elevation of blood carboxyhemoglobin (COHb) levels. We investigated the effects of a subtoxic dose of acetaminophen (APAP) on the metabolic elimination of DCM and COHb elevation in adult female rats. APAP, at 500 mg/kg i.p., was not hepatotoxic as measured by a lack of change in serum aspartate aminotransferase, alanine aminotransferase, and sorbitol dehydrogenase activities. In rats pretreated with APAP at this dose, the COHb elevation resulting from administration of DCM (3 mmol/kg i.p.) was enhanced significantly. Also blood DCM levels were reduced, and its disappearance from blood appeared to be increased. Hepatic CYP2E1-mediated activities measured with chlorzoxazone, p-nitrophenol, and p-nitroanisole as substrates were all induced markedly in microsomes of rats treated with APAP. Aminopyrine N-demethylase activity was also increased slightly, but significantly. Western blot analysis showed that APAP treatment induced the expression of CYP2E1 and CYP3A proteins. Neither hepatic glutathione contents nor glutathione S-transferase activity was changed by the dose of APAP used. The results indicate that, contrary to the well known hepatotoxic effects of this drug at large doses, a subtoxic dose of APAP may induce CYP2E1, and to a lesser degree, CYP3A expression. This is the first report that APAP can increase cytochrome P450 (P450)-mediated hepatic metabolism and the resulting toxicity of a xenobiotic in the whole animal. The pharmacological/toxicological significance of induction of P450s by a subtoxic dose of APAP is discussed.

Footnotes

  • doi:10.1124/dmd.107.015545.

  • ABBREVIATIONS: APAP, acetaminophen; P450, cytochrome P450; DCM, dichloromethane, CH2Cl2; GSH, glutathione; CO, carbon monoxide; COHb, carboxyhemoglobin; SDH, sorbitol dehydrogenase; AST, aspartate aminotransferase; ALT, alanine aminotransferase; ENPP, 1,2-epoxy-3-(p-nitrophenoxy)-propane; GST, glutathione S-transferase; PBS, phosphate-buffered saline.

    • Received March 2, 2007.
    • Accepted July 3, 2007.
  • 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: 35 (10)
Drug Metabolism and Disposition
Vol. 35, Issue 10
1 Oct 2007
  • 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.
Induction of Hepatic CYP2E1 by a Subtoxic Dose of Acetaminophen in Rats: Increase in Dichloromethane Metabolism and Carboxyhemoglobin Elevation
(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 Hepatic CYP2E1 by a Subtoxic Dose of Acetaminophen in Rats: Increase in Dichloromethane Metabolism and Carboxyhemoglobin Elevation

Su N. Kim, Ji Y. Seo, Da W. Jung, Min Y. Lee, Young S. Jung and Young C. Kim
Drug Metabolism and Disposition October 1, 2007, 35 (10) 1754-1758; DOI: https://doi.org/10.1124/dmd.107.015545

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 Hepatic CYP2E1 by a Subtoxic Dose of Acetaminophen in Rats: Increase in Dichloromethane Metabolism and Carboxyhemoglobin Elevation

Su N. Kim, Ji Y. Seo, Da W. Jung, Min Y. Lee, Young S. Jung and Young C. Kim
Drug Metabolism and Disposition October 1, 2007, 35 (10) 1754-1758; DOI: https://doi.org/10.1124/dmd.107.015545
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
    • 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 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 © 2021 by the American Society for Pharmacology and Experimental Therapeutics