ArticleScientific reports2015
Acetaminophen cytotoxicity is ameliorated in a human liver organotypic co-culture model.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 47 citations in OpenAlex.
- Article
- Novel emerging cell and organoid systems for the study of drug metabolism and toxicity in humans.Drug metabolism and disposition: the biological fate of chemicals · 2025Review
- Vascularized liver-on-a-chip model to investigate nicotine-induced dysfunction.Biomicrofluidics · 2023Article
- Liver dECM-Gelatin Composite Bioink for Precise 3D Printing of Highly Functional Liver Tissues.Journal of functional biomaterials · 2023Article
- Metabolism of Acetaminophen by Enteric Epithelial Cells Mitigates Hepatocellular Toxicity In Vitro.Journal of clinical medicine · 2023Article
- Engineered human liver based on pullulan-dextran hydrogel promotes mice survival after liver failure.Materials today. Bio · 2023Article
- Article
- Quercetin Liposomal Nanoformulation for Ischemia and Reperfusion Injury Treatment.Pharmaceutics · 2022Article
- Toxicity of the acetyl-para-aminophenol group of medicines to intact intervertebral disc tissue cells.Experimental and therapeutic medicine · 2021Article
- (+)-Clausenamide protects against drug-induced liver injury by inhibiting hepatocyte ferroptosis.Cell death & disease · 2020Article
- Article
- Protective effects of phenolic acids on mercury-induced DNA damage in precision-cut kidney slices.Iranian journal of basic medical sciences · 2019Article
- A Cell Culture Platform to Maintain Long-term Phenotype of Primary Human Hepatocytes and Endothelial Cells.Cellular and molecular gastroenterology and hepatology · 2018Article
- Liver 'organ on a chip'.Experimental cell research · 2018Review
- 4-Hydroxyphenylacetic Acid Prevents Acute APAP-Induced Liver Injury by Increasing Phase II and Antioxidant Enzymes in Mice.Frontiers in pharmacology · 2018Article
- A Review of the Inhibition of the Mitochondrial ATP Synthase by IF1Frontiers in physiology · 2018Review
- Multiscale cytometry and regulation of 3D cell cultures on a chip.Nature communications · 2017Article
- Bioprinted 3D vascularized tissue model for drug toxicity analysis.Biomicrofluidics · 2017Article
- Human Stem Cell-Derived Endothelial-Hepatic Platform for Efficacy Testing of Vascular-Protective Metabolites from Nutraceuticals.Stem cells translational medicine · 2017Article
- Low-dose acetaminophen induces early disruption of cell-cell tight junctions in human hepatic cells and mouse liver.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Organotypic liver culture models for hepatotoxicity studies that mimic in vivo hepatic functionality could help facilitate improved strategies for early safety risk assessment during drug development. Interspecies differences in drug sensitivity and mechanistic profiles, low predictive capacity, and limitations of conventional monocultures of human hepatocytes, with high attrition rates remain major challenges. Herein, we show stable, cell-type specific phenotype/cellular polarity with differentiated functionality in human hepatocyte-like C3A cells (enhanced CYP3A4 activity/albumin synthesis) when in co-culture with human vascular endothelial cells (HUVECs), thus demonstrating biocompatibility and relevance for evaluating drug metabolism and toxicity. In agreement with in vivo studies, acetaminophen (APAP) toxicity was most profound in HUVEC mono-cultures; whilst in C3A:HUVEC co-culture, cells were less susceptible to the toxic effects of APAP, including parameters of oxidative stress and ATP depletion, altered redox homeostasis, and impaired respiration. This resistance to APAP is also observed in a primary human hepatocyte (PHH) based co-culture model, suggesting bidirectional communication/stabilization between different cell types. This simple and easy-to-implement human co-culture model may represent a sustainable and physiologically-relevant alternative cell system to PHHs, complementary to animal testing, for initial hepatotoxicity screening or mechanistic studies of candidate compounds differentially targeting hepatocytes and endothelial cells.
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Registered trials
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.