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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 of genes implicated in methapyrilene-induced hepatotoxicity by comparing differential gene expression

J Todd Auman1, Jeff Chou, Kevin Gerrish

  • 1National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA.

Environmental Health Perspectives
|April 24, 2007
PubMed
Abstract

Insights

Comparing gene expression in target and non-target tissues helps identify toxicity-related genes. Analyzing temporal patterns with EPIG aids in pinpointing key transcript alterations linked to toxic effects.

Area of Science:

  • Toxicogenomics
  • Gene expression analysis
  • Computational biology

Background:

  • Toxicogenomics studies often yield numerous transcript alterations, complicating the identification of key toxicity-related genes.
  • Distinguishing between direct toxicity effects and secondary responses is a significant challenge.

Purpose of the Study:

  • To compare gene expression changes in non-target tissues versus target tissues for toxicity.
  • To identify specific genes associated with observed toxicological outcomes.

Main Methods:

  • Male rats were administered the hepatotoxicant methapyrilene at varying doses.
  • Liver and kidney tissues were collected at multiple time points (24 hours, 3 doses, 7 doses) for gene expression analysis.
  • The EPIG (extracting gene expression patterns and identifying co-expressed genes) program was utilized to analyze temporal gene expression patterns.

Main Results:

  • High-dose methapyrilene induced dose-dependent hepatic damage, with no observed kidney lesions.
  • Thousands of gene expression changes were detected in the liver, while fewer changes were noted in the kidney.
  • EPIG analysis revealed gene expression patterns correlated with toxicity, including those related to endoplasmic reticulum stress and the unfolded protein response.

Conclusions:

  • Integrating dose, time, and tissue information into gene expression analysis aids in filtering out non-implicated genes.
  • This approach allows for a focused identification of genes directly related to toxicological processes.
  • The study successfully identified key genes associated with methapyrilene-induced hepatotoxicity.

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