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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

Identification and categorization of liver toxicity markers induced by a related pair of drugs

Ching-Wei Chang1, Frederick A Beland, Wade M Hines

  • 1Division of Personalized Nutrition and Medicine, National Center for Toxicological Research, FDA, Jefferson, AR 72079, USA;

International Journal of Molecular Sciences
|August 17, 2011
PubMed

Insights

This study identified potential genomic biomarkers for drug-induced liver injury (DILI) by comparing entacapone and tolcapone in rats. The aminoacyl-tRNA biosynthesis pathway and the Vars2 gene were highlighted as significant indicators of liver toxicity.

Area of Science:

  • Pharmacogenomics
  • Toxicology
  • Biomarker Discovery

Background:

  • Drug-induced liver injury (DILI) is a major cause of drug withdrawal and development failure.
  • Identifying reliable biomarkers for DILI is crucial for drug safety and development.
  • This study investigates genomic differences between a non-liver toxic drug (entacapone) and a hepatotoxic drug (tolcapone).

Purpose of the Study:

  • To develop an approach for identifying potential liver toxicity genomic biomarkers.
  • To compare the in vivo biochemical effects of entacapone and tolcapone in rat liver and plasma.
  • To pinpoint specific genes and pathways associated with tolcapone-induced hepatotoxicity.

Main Methods:

  • Molecular analysis of rat liver and plasma samples.
  • Statistical analysis to compare drug effects.
  • Gene and pathway selection based on a classification scheme.

Main Results:

  • 695 genes and 61 pathways were identified.
  • Five pathways were specific to tolcapone treatment.
  • The Vars2 gene and the aminoacyl-tRNA biosynthesis pathway were significantly associated with tolcapone-induced liver injury in affected animals.

Conclusions:

  • The study successfully identified potential genomic biomarkers for DILI.
  • The aminoacyl-tRNA biosynthesis pathway and Vars2 gene may serve as predictive markers for tolcapone hepatotoxicity.
  • This approach can aid in the early detection of liver toxicity during drug development.
Keywords:
biomarkerentacaponegenomicliver toxicitypersonalized medicinepopulation heterogeneitytolcapone

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