Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Idiosyncratic drug hepatotoxicity.

Neil Kaplowitz1

  • 1Research Center for Liver Disease, Keck School of Medicine, University of Southern California 2011 Zonal Avenue, HMR101, Los Angeles, California 90033, USA.

Nature Reviews. Drug Discovery
|June 3, 2005
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Bile acids in liver and gastrointestinal cancer.

Seminars in cancer biology·2025
Same author

Early oxidative protein modifications and gut damage/leakiness contribute to drug-induced acute liver failure.

Clinical and molecular hepatology·2025
Same author

Hepatic LRP-1 plays an important role in amyloidosis in Alzheimer's disease mice: Potential role in chronic heavy alcohol feeding.

Neurobiology of disease·2024
Same author

Mitochondrial P-JNK target, SAB (SH3BP5), in regulation of cell death.

Frontiers in cell and developmental biology·2024
Same author

Oral magnesium prevents acetaminophen-induced acute liver injury by modulating microbial metabolism.

Cell host & microbe·2023
Same author

Clinical presentation, causative drugs and outcome of patients with autoimmune features in two prospective DILI registries.

Liver international : official journal of the International Association for the Study of the Liver·2023

Idiosyncratic drug hepatotoxicity is a significant challenge in drug development, often leading to withdrawals. This review explores predictive signals, monitoring strategies, and the pathophysiology of drug-induced liver injury.

Area of Science:

  • Pharmacology
  • Hepatology
  • Toxicology

Background:

  • Idiosyncratic drug hepatotoxicity (IDH) is a primary concern in clinical drug development and a frequent reason for drug withdrawals.
  • Predicting and preventing IDH remains a significant challenge, impacting patient safety and drug efficacy.

Purpose of the Study:

  • To review the clinical manifestations and predictive signals of IDH, focusing on early and reversible injury.
  • To assess the effectiveness of monitoring strategies in preventing IDH, using troglitazone as an example.
  • To discuss the limitations of preclinical toxicology in predicting IDH and propose improvements.
  • To examine the pathophysiology of experimental drug-induced liver injury, particularly acetaminophen toxicity, and its relation to innate immunity and cell-death pathways.

Main Methods:

Related Experiment Videos

  • Literature review of clinical signatures, predictive signals, and monitoring in drug development.
  • Analysis of case studies, including troglitazone, to illustrate IDH.
  • Examination of preclinical toxicology limitations and potential enhancements.
  • Review of current research on the pathophysiology of drug-induced liver injury, focusing on acetaminophen.

Main Results:

  • Clinical signatures and predictive signals for IDH exist, especially for low-grade, reversible injury.
  • Monitoring plays a crucial role in preventing IDH, as demonstrated by case examples.
  • Preclinical toxicology models often fail to predict idiosyncratic reactions, highlighting a gap in current methods.
  • The innate immune system and cell-death pathways are implicated in acetaminophen-induced liver injury, offering potential therapeutic targets.

Conclusions:

  • Understanding clinical signatures and implementing effective monitoring are key to managing IDH.
  • Improvements in preclinical models are needed to better predict idiosyncratic drug reactions.
  • Further research into the pathophysiology of drug-induced liver injury, including immune system roles, is essential for identifying human risk factors and mechanisms.