ArticlePloS one2020
A comparison of hepato-cellular in vitro platforms to study CYP3A4 induction.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
23 citing papers in PubMed, 38 citations in OpenAlex.
- Dose-dependent hepatotoxicity of hydrogen peroxide in HepG2 cells and its modulation by CYP450 induction.FEBS open bio · 2026Article
- Hepatocyte Models for Metabolic Dysfunction-Associated Steatotic Liver Disease: A Comparative Analysis of Non-HepG2 Cell Models.International journal of molecular sciences · 2026Review
- Evaluation of in vitro toxicity of common phytochemicals included in weight loss supplements usingFEBS open bio · 2026Article
- 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
- Herbal Weight Loss Supplements Induce Metabolomic In Vitro Changes Indicative of Oxidative Stress.Metabolites · 2025Article
- Visualization of CYP3A4 expression at both mRNA and protein levels simultaneously at single cell resolution in various conditions using RNAscope combined with immunofluorescence.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Review
- Changes in cultivation parameters impact cytochrome P450 gene transcription in HepaRG cells: implications forFrontiers in pharmacology · 2025Article
- Advancements in theFrontiers in toxicology · 2025Review
- Organ chips with integrated multifunctional sensors enable continuous metabolic monitoring at controlled oxygen levels.Biosensors & bioelectronics · 2024Article
- Advances in drug-induced liver injury research: in vitro models, mechanisms, omics and gene modulation techniques.Cell & bioscience · 2024Review
- Hepatic spheroid-on-a-chip: Fabrication and characterization of a spheroid-basedBiomicrofluidics · 2024Article
- Analysis of reproducibility and robustness of OrganoPlate® 2-lane 96, a liver microphysiological system for studies of pharmacokinetics and toxicological assessment of drugs.Toxicology in vitro : an international journal published in association with BIBRA · 2022Article
- Culture of Cancer Cells at Physiological Oxygen Levels Affects Gene Expression in a Cell-Type Specific Manner.Biomolecules · 2022Article
- Silibinin Suppresses the Hyperlipidemic Effects of the ALK-Tyrosine Kinase Inhibitor Lorlatinib in Hepatic Cells.International journal of molecular sciences · 2022Article
- Bioactive xanthones, benzophenones and biphenyls from mangosteen root with potential anti-migration against hepatocellular carcinoma cells.Scientific reports · 2022Article
- Implementing organ-on-chip in a next-generation risk assessment of chemicals: a review.Archives of toxicology · 2022Review
- CYP450 drug inducibility in NAFLD via an in vitro hepatic model: Understanding drug-drug interactions in the fatty liver.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Article
- Prediction of hepatic drug clearance with a human microfluidic four-cell liver acinus microphysiology system.Toxicology · 2021Article
- Impact of senescence on the transdifferentiation process of human hepatic progenitor-like cells.World journal of stem cells · 2021Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
In vitro studies of drug toxicity and drug-drug interactions are crucial for drug development efforts. Currently, the utilization of primary human hepatocytes (PHHs) is the de facto standard for this purpose, due to their functional xenobiotic response and drug metabolizing CYP450 enzyme metabolism. However, PHHs are scarce, expensive, require laborious maintenance, and exhibit lot-to-lot heterogeneity. Alternative human in vitro platforms include hepatic cell lines, which are easy to access and maintain, and induced pluripotent stem cell (iPSC) derived hepatocytes. In this study, we provide a direct comparison of drug induced CYP3A4 and PXR expression levels of PHHs, hepatic cell lines Huh7 and HepG2, and iPSC derived hepatocyte like cells. Confluently cultured Huh7s exhibited an improved CYP3A4 expression and were inducible by up to 4.9-fold, and hepatocytes differentiated from human iPSCs displayed a 3.3-fold CYP3A4 induction. In addition, an increase in PXR expression levels was observed in both hepatic cell lines and iPSC derived hepatocytes upon rifampicin treatment, whereas a reproducible increase in PXR expression was not achieved in PHHs. Our results indicate that both hepatoma originated cell lines and iPSCs may provide alternative sources to primary hepatocytes, providing reliable and reproducible results for CYP3A4/PXR metabolism, upon in vitro maturation. This study may serve as a guide for the selection of suitable and feasible in vitro platforms for drug-drug interaction and toxicology studies.
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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.