ArticleArchives of toxicology2018
Dynamic imaging of adaptive stress response pathway activation for prediction of drug induced liver injury.
Article in Archives of toxicology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
- Huashi Baidu formula may attenuate adriamycin-induced myocardial injury via modulating NRF2-ATF3-SRXN1 axis-mediated ferroptosis.Chinese herbal medicines · 2026Article
- Mapping safety in space: the emerging role of spatial transcriptomics in safe drug development.Frontiers in toxicology · 2026Review
- Short-Term Fasting Induces Hepatocytes' Stress Response and Increases Their Resilience.International journal of molecular sciences · 2025Article
- A computational framework to in silico screen for drug-induced hepatocellular toxicity.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Mapping Interindividual Variability of Toxicodynamics Using High-Throughput Transcriptomics and Primary Human Hepatocytes from Fifty Donors.Environmental health perspectives · 2024Article
- A network-based transcriptomic landscape of HepG2 cells uncovering causal gene-cytotoxicity interactions underlying drug-induced liver injury.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Collaborative SAR Modeling and Prospective In Vitro Validation of Oxidative Stress Activation in Human HepG2 Cells.Journal of chemical information and modeling · 2023Article
- G × E interactions as a basis for toxicological uncertainty.Archives of toxicology · 2023Article
- Identifying multiscale translational safety biomarkers using a network-based systems approach.iScience · 2023Article
- Identification of Drug-Induced Liver Injury Biomarkers from Multiple Microarrays Based on Machine Learning and Bioinformatics Analysis.International journal of molecular sciences · 2022Article
- Stimulation of de novo glutathione synthesis by nitrofurantoin for enhanced resilience of hepatocytes.Cell biology and toxicology · 2022Article
- Antipsychotic Drug Aripiprazole Protects Liver Cells from Oxidative Stress.International journal of molecular sciences · 2022Article
- Dynamic modeling of Nrf2 pathway activation in liver cells after toxicant exposure.Scientific reports · 2022Article
- Towards an advanced testing strategy for genotoxicity using image-based 2D and 3D HepG2 DNA damage response fluorescent protein reporters.Mutagenesis · 2022Article
- Hepatic Organoid-Based High-Content Imaging Boosts Evaluation of Stereoisomerism-Dependent Hepatotoxicity of Stilbenes in Herbal Medicines.Frontiers in pharmacology · 2022Article
- HiPSC-Derived Hepatocyte-like Cells Can Be Used as a Model for Transcriptomics-Based Study of Chemical Toxicity.Toxics · 2021Article
- Preclinical models of idiosyncratic drug-induced liver injury (iDILI): Moving towards prediction.Acta pharmaceutica Sinica. B · 2021Review
- Fluorescent tagging of endogenous Heme oxygenase-1 in human induced pluripotent stem cells for high content imaging of oxidative stress in various differentiated lineages.Archives of toxicology · 2021Article
- Mitochondrial stress response in drug-induced liver injury.Molecular biology reports · 2021Review
- Oxidative Stress in Drug-Induced Liver Injury (DILI): From Mechanisms to Biomarkers for Use in Clinical Practice.Antioxidants (Basel, Switzerland) · 2021Review
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Drug-induced liver injury remains a concern during drug treatment and development. There is an urgent need for improved mechanistic understanding and prediction of DILI liabilities using in vitro approaches. We have established and characterized a panel of liver cell models containing mechanism-based fluorescent protein toxicity pathway reporters to quantitatively assess the dynamics of cellular stress response pathway activation at the single cell level using automated live cell imaging. We have systematically evaluated the application of four key adaptive stress pathway reporters for the prediction of DILI liability: SRXN1-GFP (oxidative stress), CHOP-GFP (ER stress/UPR response), p21 (p53-mediated DNA damage-related response) and ICAM1 (NF-κB-mediated inflammatory signaling). 118 FDA-labeled drugs in five human exposure relevant concentrations were evaluated for reporter activation using live cell confocal imaging. Quantitative data analysis revealed activation of single or multiple reporters by most drugs in a concentration and time dependent manner. Hierarchical clustering of time course dynamics and refined single cell analysis allowed the allusion of key events in DILI liability. Concentration response modeling was performed to calculate benchmark concentrations (BMCs). Extracted temporal dynamic parameters and BMCs were used to assess the predictive power of sub-lethal adaptive stress pathway activation. Although cellular adaptive responses were activated by non-DILI and severe-DILI compounds alike, dynamic behavior and lower BMCs of pathway activation were sufficiently distinct between these compound classes. The high-level detailed temporal- and concentration-dependent evaluation of the dynamics of adaptive stress pathway activation adds to the overall understanding and prediction of drug-induced liver liabilities.
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