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

Published on: January 31, 2022

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Systems toxicology of chemically induced liver and kidney injuries: histopathology-associated gene co-expression

Jerez A Te1, Mohamed Diwan M AbdulHameed1, Anders Wallqvist1

  • 1Department of Defense Biotechnology High Performance Computing Software Applications Institute, Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Materiel Command, Fort Detrick, MD, 21702, USA.

Journal of Applied Toxicology : JAT
|January 5, 2016
PubMed

Insights

New biomarkers link chemical exposures to organ damage. Gene expression modules accurately predict liver and kidney injury severity and type, aiding non-invasive diagnostics.

Area of Science:

  • Toxicology
  • Genomics
  • Biomarker Discovery

Background:

  • Assessing organ injuries from chemical exposures lacks non-invasive diagnostic tests.
  • Biomarkers are needed to map chemical injuries to histopathology outcomes for precise diagnostics.

Purpose of the Study:

  • To identify gene expression modules associated with chemical-induced organ injuries.
  • To develop a protocol for classifying liver and kidney histopathology endpoints using these modules.

Main Methods:

  • Utilized the Genomics Assisted Toxicity Evaluation System (TG-GATEs) database.
  • Analyzed organ-specific gene expression data from Sprague-Dawley rats exposed to chemicals.
  • Correlated gene module activation with dose- and time-dependent histopathological damage.

Main Results:

  • Identified gene modules specific to 11 liver and 8 kidney histopathology endpoints.
  • Module activation correlated with histopathological damage severity in a dose-dependent manner.
  • Modules distinguished between different injury types and were tissue-specific (liver/kidney).

Conclusions:

  • Developed gene modules linking toxic exposures to molecular initiating events and organ damage.
  • These modules provide a foundation for developing robust, non-invasive diagnostic tests for chemical-induced organ injuries.
Keywords:
adverse outcome pathwaysco-expression moduleshepatotoxicityhistopathologynephrotoxicitysystems toxicologytoxicogenomics

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