ArticleArchives of toxicology2020
Robustness testing and optimization of an adverse outcome pathway on cholestatic liver injury.
Article in Archives of toxicology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- The First Steps on AOPs' Concepts, Development, and Applications in Teratology.Methods in molecular biology (Clifton, N.J.) · 2024Pooled it
- A collagen hydrogel-based 3D Heparg model for enhanced hepatocyte function and assessment of cholestatic drug-induced liver injury.Archives of toxicology · 2026Article
- Exploring the potential of liver microphysiological systems of varied configurations to model cholestatic chemical effects.Archives of toxicology · 2026Article
- TGFBI promotes liver fibrosis through remodeling the profibrotic microenvironment by a positive feedback regulatory loop.Communications biology · 2026Article
- Cell-based approaches for the mechanistic understanding of drug-induced cholestatic liver injury.Archives of toxicology · 2025Review
- Inhibition of RAC1 activator DOCK2 ameliorates cholestatic liver injury via regulating macrophage polarisation and hepatic stellate cell activation.Biology direct · 2025Article
- From hazard to risk prioritization: a case study to predict drug-induced cholestasis using physiologically based kinetic modeling.Archives of toxicology · 2024Article
- Unraveling the mechanisms underlying drug-induced cholestatic liver injury: identifying key genes using machine learning techniques on human in vitro data sets.Archives of toxicology · 2023Article
- Integrating Concentration-Dependent Toxicity Data and Toxicokinetics To Inform Hepatotoxicity Response Pathways.Environmental science & technology · 2023Article
- Metabolism-Disrupting Chemicals Affecting the Liver: Screening, Testing, and Molecular Pathway Identification.International journal of molecular sciences · 2023Review
- Systematic comparison of experimental and human obstructive cholestasis reveals conservation of canonical pathway activation and biomarkers relevant for cholestatic liver disease.Genes & diseases · 2023Article
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- Population pharmacokinetic model to generate mechanistic insights in bile acid homeostasis and drug-induced cholestasis.Archives of toxicology · 2022Article
- Mitochondria as the Target of Hepatotoxicity and Drug-Induced Liver Injury: Molecular Mechanisms and Detection Methods.International journal of molecular sciences · 2022Review
- Human menstrual blood-derived stem cell transplantation suppresses liver injury in DDC-induced chronic cholestasis.Stem cell research & therapy · 2022Article
- Adverse Outcome Pathways as Versatile Tools in Liver Toxicity Testing.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Involvement of oxidative species in cyclosporine-mediated cholestasis.Frontiers in pharmacology · 2022Review
- Primary Human Hepatocyte Spheroids as Tools to Study the Hepatotoxic Potential of Non-Pharmaceutical Chemicals.International journal of molecular sciences · 2021Article
- Dataset on transcriptomic profiling of cholestatic liver injury induced by food additives and a cosmetic ingredient.Data in brief · 2021Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adverse outcome pathways (AOPs) have been recently introduced as tools to map the mechanisms underlying toxic events relevant for chemical risk assessment. AOPs particularly depict the linkage between a molecular initiating event and an adverse outcome through a number of intermediate key events. An AOP has been previously introduced for cholestatic liver injury. The objective of this study was to test the robustness of this AOP for different types of cholestatic insult and the in vitro to in vivo extrapolation. For this purpose, in vitro samples from human hepatoma HepaRG cell cultures were exposed to cholestatic drugs (i.e. intrahepatic cholestasis), while in vivo samples were obtained from livers of cholestatic mice (i.e. extrahepatic cholestasis). The occurrence of cholestasis in vitro was confirmed through analysis of bile transporter functionality and bile acid analysis. Transcriptomic analysis revealed inflammation and oxidative stress as key events in both types of cholestatic liver injury. Major transcriptional differences between intrahepatic and extrahepatic cholestatic liver insults were observed at the level of cell death and metabolism. Novel key events identified by pathway analysis included endoplasmic reticulum stress in intrahepatic cholestasis, and autophagy and necroptosis in both intrahepatic as extrahepatic cholestasis. This study demonstrates that AOPs constitute dynamic tools that should be frequently updated with new input information.
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