ArticleScientific reports2020
New insights in acetaminophen toxicity: HMGB1 contributes by itself to amplify hepatocyte necrosis in vitro through the TLR4-TRIF-RIPK3 axis.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- The redox-sensitive protein HMGB1: intracellular and extracellular roles.Experimental & molecular medicine · 2026Review
- Adipose-Derived Mesenchymal Stem Cells Improve Acute Liver Injury: A Mechanistic Study Based on the TLR4/MyD88/NF-κB Pathway.International journal of molecular sciences · 2025Article
- In vitro liver models for toxicological research.Drug metabolism and pharmacokinetics · 2025Review
- Deciphering per- and polyfluoroalkyl substances mode of action: comparative gene expression analysis in human liver spheroids.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Emerging Roles of High-mobility Group Box-1 in Liver Disease.Journal of clinical and translational hepatology · 2024Review
- HMGB1 as an extracellular pro-inflammatory cytokine: Implications for drug-induced organic damage.Cell biology and toxicology · 2024Review
- Deletion of Glyoxalase 1 Exacerbates Acetaminophen-Induced Hepatotoxicity in Mice.Antioxidants (Basel, Switzerland) · 2024Article
- Article
- Acetaminophen Hepatotoxicity: Paradigm for Understanding Mechanisms of Drug-Induced Liver Injury.Annual review of pathology · 2024Review
- TRIF-dependent signaling and its role in liver diseases.Frontiers in cell and developmental biology · 2024Review
- An Insight into Different Experimental Models used for Hepatoprotective Studies: A Review.Current drug discovery technologies · 2024Review
- Deletion of Glyoxalase 1 exacerbates acetaminophen-induced hepatotoxicity in mice.bioRxiv : the preprint server for biology · 2023Article
- Molecular mechanism and research progress on pharmacology of ferulic acid in liver diseases.Frontiers in pharmacology · 2023Review
- A novel histone deacetylase inhibitor exerts promising anti-breast cancer activity via triggering AIFM1-dependent programmed necrosis.Cancer communications (London, England) · 2022Article
- Article
- Extract ofMolecules (Basel, Switzerland) · 2021Article
- Liver regeneration and inflammation: from fundamental science to clinical applications.Nature reviews. Molecular cell biology · 2021Review
- Functional crosstalk between myeloid Foxo1-β-catenin axis and Hedgehog/Gli1 signaling in oxidative stress response.Cell death and differentiation · 2021Article
- Review
- N-acetylcysteine and glycyrrhizin combination: Benefit outcome in a murine model of acetaminophen-induced liver failure.World journal of hepatology · 2020Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Extracellular release of HMGB1 contributes to acetaminophen-induced liver injury. HMGB1 acts as a danger-associated molecular patterns during this toxic process but the mechanisms of action and targeted cells are incompletely defined. Here we studied, in vitro, the role of HMGB1 in amplifying the acetaminophen-induced hepatocyte necrosis process. Using cultured HepaRG cells, primary human hepatocytes and selective chemical inhibitors we evaluated acetaminophen-induced toxicity. We confirmed that addition of acetaminophen induced HepaRG cell death and HMGB1 release. We showed that inhibition of HMGB1 decreased acetaminophen-induced HepaRG cell death, suggesting a feedforward effect. We provide the first evidence that exposure of HepaRG cells to recombinant human HMGB1 (rhHMGB1) also resulted in cell death. Moreover, we found that both acetaminophen and rhHMGB1 induced programmed HepaRG cell necrosis through a RIPK3-dependent mechanism. By using TLR4 blocking antibody, we demonstrated the reduction of the HepaRG cell death induced by acetaminophen and rhHMGB1. Furthermore, inhibition of TRIF, known to induce a RIPK3-dependent cell death, reduced rhHMGB1-induced HepaRG cell death. Our data support that released HMGB1 from acetaminophen-stressed hepatocytes induced necrosis of neighboring hepatocytes by TLR4-TRIF-RIPK3- pathway. This in vitro study gives new insights in the role of HMGB1 in the amplification of acetaminophen-induced toxicity.
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