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
Molecular Pharmacology
  • 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
Molecular Pharmacology

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 molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
OtherArticle

A potential role for SerpinA3N in acetaminophen-induced hepatotoxicity

Melanie Tran, Jianguo Wu, Li Wang and Dong-Ju Shin
Molecular Pharmacology January 12, 2021, MOLPHARM-AR-2020-000117; DOI: https://doi.org/10.1124/molpharm.120.000117
Melanie Tran
1Physiology and Neurobiology, University of Connecticut, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: metran@uchc.edu
Jianguo Wu
1Physiology and Neurobiology, University of Connecticut, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Li Wang
2Department of Internal Medicine, Yale University, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dong-Ju Shin
1Physiology and Neurobiology, University of Connecticut, United States of America
  • 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

Acetaminophen (APAP) is a commonly used pain and fever reliver but is also the most frequent cause of drug induced liver injury. The mechanism pertaining acetaminophen toxicity has been well documented, while mechanisms of hepatotoxicity are not well established. Serine (or cysteine) peptidase inhibitor, clade A, member 3N (SerpinA3N), a serine protease inhibitor, is synthesized in the liver but the role of SerpinA3N in relation to APAP-induced liver injury is not known. Wildtype (WT) and hepatocyte SerpinA3N knockout (HKO) mice were injected intraperitoneally with a single dose of phosphate buffered solution (PBS) or APAP (400 mg/kg) for 12 hours, and markers of liver injury, cell death, inflammation and autophagy were assessed. SerpinA3N expression was highly induced in mice with APAP overdose. SerpinA3N HKO mice had diminished liver injury and necrosis as shown by reduced alanine aminotransferase (ALT) and interleukin (IL)-6 levels, accompanied by suppressed inflammatory cytokines and reduced neutrophil infiltration. The reduced oxidative stress was associated with enhanced antioxidant enzyme capabilities. Taken together, hepatocyte SerpinA3N deficiency reduced APAP-induced liver injury by ameliorating inflammation and modulating the 5' AMP-activated protein kinase-unc-51 like autophagy activating kinase 1 (AMPK-ULK1) signaling pathway. Our study provides novel insights into a potential role for SerpinA3N in APAP-induced liver injury.

Significance Statement Our studies indicate that SerpinA3N may have a pathophysiological role in modulating APAP-induced liver injury. More specifically, mice with hepatic deletion of SerpinA3N suppressed inflammation and liver injury to reduce APAP induced hepatotoxicity. Controlling the inflammatory response offers possible approaches for novel therapeutics, therefore understanding the pathophysiological role of SerpinA3N in inducing liver toxicity may add to the development of more efficacious treatments.

  • inflammation
  • liver injury/toxicity (DILI)
  • liver physiology/models
  • macrophages
  • necrosis
  • Copyright © 2020 American Society for Pharmacology and Experimental Therapeutics
PreviousNext
Back to top

In this issue

Molecular Pharmacology: 99 (2)
Molecular Pharmacology
Vol. 99, Issue 2
1 Feb 2021
  • 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 Molecular Pharmacology 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.
A potential role for SerpinA3N in acetaminophen-induced hepatotoxicity
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
OtherArticle

SerpinA3N and drug induced liver injury

Melanie Tran, Jianguo Wu, Li Wang and Dong-Ju Shin
Molecular Pharmacology January 12, 2021, MOLPHARM-AR-2020-000117; DOI: https://doi.org/10.1124/molpharm.120.000117

Citation Manager Formats

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

SerpinA3N and drug induced liver injury

Melanie Tran, Jianguo Wu, Li Wang and Dong-Ju Shin
Molecular Pharmacology January 12, 2021, MOLPHARM-AR-2020-000117; DOI: https://doi.org/10.1124/molpharm.120.000117
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
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • P2X7 Positive Modulator Structure-Activity Relationship
  • Predicting Drug Interactions with ENT1 and ENT2
  • GABAAR Molecular Identity in Oligodendrocytes
Show more Article

Similar Articles

  • 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 Molecular Pharmacology
  • 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
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

Copyright © 2021 by the American Society for Pharmacology and Experimental Therapeutics