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
Journal of Pharmacology and Experimental Therapeutics
  • 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
Journal of Pharmacology and Experimental Therapeutics

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 jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleTOXICOLOGY

The Nitric Oxide Donor, O2-Vinyl 1-(Pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (V-PYRRO/NO), Protects against Cadmium-Induced Hepatotoxicity in Mice

Jie Liu, Wei Qu, Joseph E. Saavedra and Michael P. Waalkes
Journal of Pharmacology and Experimental Therapeutics July 2004, 310 (1) 18-24; DOI: https://doi.org/10.1124/jpet.103.065003
Jie Liu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wei Qu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joseph E. Saavedra
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael P. Waalkes
  • 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

The nitric oxide (NO) donor, O2-vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (V-PYRRO/NO), is metabolized by P450 enzymes to release NO within the liver and is effective in protecting against hepatotoxicity of endotoxin and acetaminophen. This study examined the effects of V-PYRRO/NO on cadmium (Cd) hepatotoxicity in mice. Mice were given multiple injections of V-PYRRO/NO (10 mg/kg, s.c. at 2-h intervals) before and after a hepatotoxic dose of Cd (3.7 mg/kg Cd as CdCl2, i.p.). V-PYRRO/NO administration reduced Cd-induced hepatotoxicity as evidenced by reduced serum alanine aminotransferase activity, improved pathology, and reduced hepatic lipid peroxidation. The protection by V-PYRRO/NO was not mediated by altered Cd distribution to the liver or within hepatic subcellular fractions. Similar inductions of metallothionein, a metal-binding protein, were observed in mice receiving Cd alone or Cd plus V-PYRRO/NO. Real-time reverse transcription-polymerase chain reaction analysis revealed that V-PYRRO/NO administration suppressed the expression of inflammation-related genes such as macrophage inflammatory protein-2, CXC chemokine, thrombospondin-1, intracellular adhesion molecular-1, and interleukin-6. V-PYRRO/NO also suppressed the expression of acute phase protein genes and genes related to cell-death pathways, such as c-jun/AP-1, nuclear factor-κB, early response growth factor-1, heme oxygenase-1, caspase-3, growth arrest, and DNA-damaging protein-153. In summary, the liver-selective NO donor, V-PYRRO/NO, protects against Cd hepatotoxicity in mice. This protection is not mediated through altered distribution of Cd but may be related to reduced hepatic inflammation, reduced acute phase responses, and the suppression of cell-death-related components.

Footnotes

  • This project has been funded in part by the National Cancer Institute/National Institutes of Health under contract NO1-CO-12400.

  • DOI: 10.1124/jpet.103.065003.

  • ABBREVIATIONS: V-PYRRO/NO, O2-vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate; NO, nitric oxide; TNF-α, tumor necrosis factor-α; IL, interleukin; iNOS, inducible nitric-oxide synthase; ALT, alanine aminotransferase; 4-HNE, 4-hydroxy-2(E)-nonenal; MDA, malonialdehyde; MT, metallothionein; RT-PCR, reverse transcription-polymerase chain reaction; MIP-2, macrophage inflammatory protein-2; mKC, mouse chemokine; ICAM-1, intracellular cell adhesion molecule-1; HO-1, heme oxygenase-1; NF-κB, nuclear factor-κB.

    • Received December 29, 2003.
    • Accepted March 9, 2004.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

JPET 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

Journal of Pharmacology and Experimental Therapeutics: 310 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 310, Issue 1
1 Jul 2004
  • 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 Journal of Pharmacology and Experimental Therapeutics 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.
The Nitric Oxide Donor, O2-Vinyl 1-(Pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (V-PYRRO/NO), Protects against Cadmium-Induced Hepatotoxicity in Mice
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleTOXICOLOGY

The Nitric Oxide Donor, O2-Vinyl 1-(Pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (V-PYRRO/NO), Protects against Cadmium-Induced Hepatotoxicity in Mice

Jie Liu, Wei Qu, Joseph E. Saavedra and Michael P. Waalkes
Journal of Pharmacology and Experimental Therapeutics July 1, 2004, 310 (1) 18-24; DOI: https://doi.org/10.1124/jpet.103.065003

Citation Manager Formats

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

Share
Research ArticleTOXICOLOGY

The Nitric Oxide Donor, O2-Vinyl 1-(Pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (V-PYRRO/NO), Protects against Cadmium-Induced Hepatotoxicity in Mice

Jie Liu, Wei Qu, Joseph E. Saavedra and Michael P. Waalkes
Journal of Pharmacology and Experimental Therapeutics July 1, 2004, 310 (1) 18-24; DOI: https://doi.org/10.1124/jpet.103.065003
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
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Nafamostat is a potent human diamine oxidase inhibitor
  • Chemoproteomics Investigation of Testicular Toxicity with BTK Inhibitor
  • Bosentan Alters Bile Salt Disposition
Show more Toxicology

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 JPET
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

Copyright © 2022 by the American Society for Pharmacology and Experimental Therapeutics