ArticleToxicological sciences : an official journal of the Society of Toxicology2018
Editor's Highlight: An Impaired Immune Tolerance Animal Model Distinguishes the Potential of Troglitazone/Pioglitazone and Tolcapone/Entacapone to Cause IDILI.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 42 citations in OpenAlex.
- Expanding the Biocatalytic Toolbox: A Singular P450 Enzyme Efficiently Produces Diverse Pharmaceutical Metabolites.ACS omega · 2026Article
- The development and characterization of a CRISPR/Cas9-mediated PD-1 functional knockout rat as a tool to study idiosyncratic drug reactions.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Assessing immune hepatotoxicity of troglitazone with a versatile liver-immune-microphysiological-system.Frontiers in pharmacology · 2024Article
- Exploiting the predictive power of educated spheroids to detect immune-mediated idiosyncratic drug-induced liver injury: the case of troglitazone.Frontiers in pharmacology · 2024Article
- Preclinical models of idiosyncratic drug-induced liver injury (iDILI): Moving towards prediction.Acta pharmaceutica Sinica. B · 2021Review
- Oxidative Stress in Drug-Induced Liver Injury (DILI): From Mechanisms to Biomarkers for Use in Clinical Practice.Antioxidants (Basel, Switzerland) · 2021Review
- An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury.Archives of toxicology · 2021Article
- The hepatotoxicity of Polygonum multiflorum: The emerging role of the immune-mediated liver injury.Acta pharmacologica Sinica · 2021Review
- Recent Advances in Models of Immune-Mediated Drug-Induced Liver Injury.Frontiers in toxicology · 2021Review
- What have we learned from animal models of idiosyncratic, drug-induced liver injury?Expert opinion on drug metabolism & toxicology · 2020Review
- Hepatocyte-Derived Exosomes Promote Liver Immune Tolerance: Possible Implications for Idiosyncratic Drug-Induced Liver Injury.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Animal models of drug-induced liver injury.Biochimica et biophysica acta. Molecular basis of disease · 2019Review
- 2018 Toxicological Sciences Papers of the Year.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Mechanistic Studies of Idiosyncratic DILI: Clinical Implications.Frontiers in pharmacology · 2019Review
- Strategies for Early Prediction and Timely Recognition of Drug-Induced Liver Injury: The Case of Cyclin-Dependent Kinase 4/6 Inhibitors.Frontiers in pharmacology · 2019Review
- Mechanisms of Inflammatory Liver Injury and Drug-Induced Hepatotoxicity.Current pharmacology reports · 2018Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
We have developed an animal model of amodiaquine-induced liver injury that has characteristics very similar to idiosyncratic drug-induced liver injury (IDILI) in humans by impairing immune tolerance using a PD1-/- mouse and cotreatment with anti-CTLA-4. In order to test the usefulness of this model as a general model for human IDILI risk, pairs of drugs with similar structures were tested, one of which is associated with a relatively high risk of IDILI and the other not. One such pair is troglitazone and pioglitazone; troglitazone has caused fatal cases of IDILI while pioglitazone is quite safe. Another pair is tolcapone and entacapone; tolcapone can cause serious IDILI; in contrast, although entacapone has been reported to cause liver injury, it is relatively safe. PD1-/- mice treated with anti-CTLA-4 and troglitazone or tolcapone displayed liver injury as determined by ALT levels and histology, while pioglitazone and entacapone showed less signs of liver injury. One possible mechanism by which drugs could induce an immune response leading to IDILI is by causing the release of danger-associated molecular pattern molecules that activate inflammasomes. We found that the supernatants from incubations of troglitazone, tolcapone, or entacapone with hepatocytes were also able to activate inflammasomes in macrophages, while the supernatant from pioglitazone incubations did not. These results are consistent with an immune mechanism for troglitazone- and tolcapone-induced IDILI and add to the evidence that this may be a general model for IDILI.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.