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Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
11:06

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro

Published on: January 31, 2022

Mitochondrial involvement in drug-induced hepatic injury

George E N Kass1

  • 1School of Biomedical and Molecular Sciences, University of Surrey, Guildford GU2 7XH, UK. g.kass@surrey.ac.uk <g.kass@surrey.ac.uk>

Chemico-Biological Interactions
|August 8, 2006
PubMed

Insights

Drug-induced liver injury is a major concern, often stemming from mitochondrial damage. This review explores how various hepatotoxic drugs target mitochondria, leading to liver cell death and injury.

Area of Science:

  • Hepatology
  • Toxicology
  • Mitochondrial Biology

Background:

  • Drug-induced liver injury (DILI) is a primary cause for drug development failure and market withdrawal.
  • Mitochondria are critical organelles involved in initiating hepatocyte cell death pathways.
  • Diverse signaling pathways converge at the mitochondria, leading to various cell death modalities.

Purpose of the Study:

  • To review the mechanisms by which hepatotoxic drugs induce liver injury.
  • To elucidate the central role of mitochondria in drug-induced hepatotoxicity.
  • To discuss how direct drug effects or indirect effects (steatosis, cholestasis) impact mitochondrial function.

Main Methods:

  • Literature review of studies on drug-induced liver injury.
  • Analysis of mechanisms targeting mitochondria in hepatotoxicity.
  • Examination of signaling pathways involved in cell death.

Main Results:

  • Hepatotoxic drugs can directly damage mitochondria or indirectly trigger cell death pathways.
  • Mitochondrial dysfunction is a common endpoint for various hepatotoxic insults.
  • Drug-induced steatosis and cholestasis contribute to mitochondrial targeting and liver injury.

Conclusions:

  • Mitochondria are key targets in drug-induced liver injury.
  • Understanding these mitochondrial mechanisms is crucial for developing safer drugs.
  • Targeting mitochondrial pathways may offer therapeutic strategies for DILI.

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