ArticleToxicological sciences : an official journal of the Society of Toxicology2025
Limitations of acetaminophen as a reference hepatotoxin for the evaluation of in vitro liver models.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Acetaminophen should be a critical reference hepatotoxin for evaluating human-relevant in vitro models.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Engineering liver disease models in vitro: emerging trends and innovations.eGastroenterology · 2025Review
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Authors and funding
8 authors.
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Abstract
Acetaminophen is commonly used as a reference hepatotoxin to demonstrate that in vitro human liver platforms can emulate features of clinical drug-induced liver injury. However, the induction of substantial cell death in these models typically requires acetaminophen concentrations (∼10 mM) far higher than blood concentrations of the drug associated with clinical hepatotoxicity (∼1 mM). Using the cytochrome P450 inhibitor 1-aminobenzotriazole, we show that acetaminophen toxicity in cultured human, mouse, and rat hepatocytes is not dependent on N-acetyl-p-benzoquinonimine formation, unlike the in vivo setting. This finding highlights the limitation of using acetaminophen as a reference hepatotoxin for the evaluation of in vitro liver models. Hence, we make recommendations on the selection of reference hepatotoxins for this purpose.
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