ArticleToxicology and applied pharmacology2016
A cellular model to study drug-induced liver injury in nonalcoholic fatty liver disease: Application to acetaminophen.
Article in Toxicology and applied pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 67 citations in OpenAlex.
- Hepatocyte Models for Metabolic Dysfunction-Associated Steatotic Liver Disease: A Comparative Analysis of Non-HepG2 Cell Models.International journal of molecular sciences · 2026Review
- Modeling fatty liver disease and progression with stem cell derived hepatocytes.Scientific reports · 2026Article
- Modeling pathogenesis and progression of metabolic dysfunction-associated steatotic liver disease and therapeutic drug screening using hESC-derived mature polarized hepatocyte organoids.Stem cell research & therapy · 2025Article
- Effects of total saikosaponins on CYP3A4 and CYP1A2 in HepaRG cells.Experimental and therapeutic medicine · 2024Article
- SARS-CoV-2 receptor ACE2 is upregulated by fatty acids in human MASH.JHEP reports : innovation in hepatology · 2024Article
- Subcellular expression of CYP2E1 in HepG2 cells impacts response to free oleic and palmitic acid.Current research in toxicology · 2024Article
- [Risk factors for metabolic dysfunction-associated fatty liver disease in the Hispanic-Mexican population.]Revista espanola de salud publica · 2023Article
- In vitro to in vivo extrapolation and high-content imaging for simultaneous characterization of chemically induced liver steatosis and markers of hepatotoxicity.Archives of toxicology · 2023Article
- Article
- Acetaminophen-Induced Hepatotoxicity in Obesity and Nonalcoholic Fatty Liver Disease: A Critical Review.Livers · 2023Article
- Development of a novel human triculture model of non-alcoholic fatty liver disease and identification of berberine as ameliorating steatosis, oxidative stress and fibrosis.Frontiers in pharmacology · 2023Article
- Customized liver organoids as an advancedInternational journal of biological sciences · 2023Review
- Article
- Acetaminophen (APAP, Paracetamol) Interferes With the First Trimester Human Fetal Ovary Development in an Ex Vivo Model.The Journal of clinical endocrinology and metabolism · 2022Article
- Recapitulating lipid accumulation and related metabolic dysregulation in human liver-derived organoids.Journal of molecular medicine (Berlin, Germany) · 2022Article
- Xenobiotic-Induced Aggravation of Metabolic-Associated Fatty Liver Disease.International journal of molecular sciences · 2022Review
- Review
- Molecular Networking for Drug Toxicities Studies: The Case of Hydroxychloroquine in COVID-19 Patients.International journal of molecular sciences · 2021Article
- Comparison of gene expression and biotransformation activity of HepaRG cells under static and dynamic culture conditions.Scientific reports · 2021Article
- High-Fidelity Drug-Induced Liver Injury Screen Using Human Pluripotent Stem Cell-Derived Organoids.Gastroenterology · 2021Article
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Obesity and nonalcoholic fatty liver disease (NAFLD) can increase susceptibility to hepatotoxicity induced by some xenobiotics including drugs, but the involved mechanisms are poorly understood. For acetaminophen (APAP), a role of hepatic cytochrome P450 2E1 (CYP2E1) is suspected since the activity of this enzyme is consistently enhanced during NAFLD. The first aim of our study was to set up a cellular model of NAFLD characterized not only by triglyceride accumulation but also by higher CYP2E1 activity. To this end, human HepaRG cells were incubated for one week with stearic acid or oleic acid, in the presence of different concentrations of insulin. Although cellular triglycerides and the expression of lipid-responsive genes were similar with both fatty acids, CYP2E1 activity was significantly increased only by stearic acid. CYP2E1 activity was reduced by insulin and this effect was reproduced in cultured primary human hepatocytes. Next, APAP cytotoxicity was assessed in HepaRG cells with or without lipid accretion and CYP2E1 induction. Experiments with a large range of APAP concentrations showed that the loss of ATP and glutathione was almost always greater in the presence of stearic acid. In cells pretreated with the CYP2E1 inhibitor chlormethiazole, recovery of ATP was significantly higher in the presence of stearate with low (2.5mM) or high (20mM) concentrations of APAP. Levels of APAP-glucuronide were significantly enhanced by insulin. Hence, HepaRG cells can be used as a valuable model of NAFLD to unveil important metabolic and hormonal factors which can increase susceptibility to drug-induced hepatotoxicity.
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