ArticleMediators of inflammation2015
Subtoxic Concentrations of Hepatotoxic Drugs Lead to Kupffer Cell Activation in a Human In Vitro Liver Model: An Approach to Study DILI.
Article in Mediators of inflammation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 45 citations in OpenAlex.
- Article
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- Unlocking the potential of flavonoid-infused drug delivery systems for diabetic wound healing with a mechanistic exploration.Inflammopharmacology · 2024Review
- Regular Consumption of Green Tea as an Element of Diet Therapy in Drug-Induced Liver Injury (DILI).Nutrients · 2024Review
- Review
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- Manjari Medika Grape Seed Extract Protects Methotrexate-Induced Hepatic Inflammation: Involvement of NF-κB/NLRP3 and Nrf2/HO-1 Signaling System.Journal of inflammation research · 2023Article
- In Vivo and In Vitro Characterization of Primary Human Liver Macrophages and Their Inflammatory State.Biomedicines · 2021Article
- 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
- Recent Advances in Models of Immune-Mediated Drug-Induced Liver Injury.Frontiers in toxicology · 2021Review
- Multi-Therapeutic Potential of Naringenin (4',5,7-Trihydroxyflavonone): Experimental Evidence and Mechanisms.Plants (Basel, Switzerland) · 2020Review
- Prolonged Lipid Accumulation in Cultured Primary Human Hepatocytes Rather Leads to ER Stress than Oxidative Stress.International journal of molecular sciences · 2020Article
- Hepatic histopathological and ultrastructural alterations induced by 10 nm silver nanoparticles.IET nanobiotechnology · 2020Article
- Hepatic Bioactivation of Skin-Sensitizing Drugs to Immunogenic Reactive Metabolites.ACS omega · 2019Article
- 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
- An Expandable Mechanopharmaceutical Device (2): Drug Induced Granulomas Maximize the Cargo Sequestering Capacity of Macrophages in the Liver.Pharmaceutical research · 2018Article
- Microscale 3D Liver Bioreactor for In Vitro Hepatotoxicity Testing under Perfusion Conditions.Bioengineering (Basel, Switzerland) · 2018Article
- Integrated Assessment of Diclofenac Biotransformation, Pharmacokinetics, and Omics-Based Toxicity in a Three-Dimensional Human Liver-Immunocompetent Coculture System.Drug metabolism and disposition: the biological fate of chemicals · 2017Article
- Evaluation of a human in vitro hepatocyte-NPC co-culture model for the prediction of idiosyncratic drug-induced liver injury: A pilot study.Toxicology reports · 2017Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Drug induced liver injury (DILI) is an idiosyncratic adverse drug reaction leading to severe liver damage. Kupffer cells (KC) sense hepatic tissue stress/damage and therefore could be a tool for the estimation of consequent effects associated with DILI. Aim of the present study was to establish a human in vitro liver model for the investigation of immune-mediated signaling in the pathogenesis of DILI. Hepatocytes and KC were isolated from human liver specimens. The isolated KC yield was 1.2 ± 0.9 × 10(6) cells/g liver tissue with a purity of >80%. KC activation was investigated by the measurement of reactive oxygen intermediates (ROI, DCF assay) and cell activity (XTT assay). The initial KC activation levels showed broad donor variability. Additional activation of KC using supernatants of hepatocytes treated with hepatotoxic drugs increased KC activity and led to donor-dependent changes in the formation of ROI compared to KC incubated with supernatants from untreated hepatocytes. Additionally, a compound- and donor-dependent increase in proinflammatory cytokines or in anti-inflammatory cytokines was detected. In conclusion, KC related immune signaling in hepatotoxicity was successfully determined in a newly established in vitro liver model. KC were able to detect hepatocyte stress/damage and to transmit a donor- and compound-dependent immune response via cytokine production.
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