ArticleChemico-biological interactions2016
Development of HepG2-derived cells expressing cytochrome P450s for assessing metabolism-associated drug-induced liver toxicity.
Article in Chemico-biological interactions, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 99 citations in OpenAlex.
- Phenotypical and functional characterization of a HepG2 cell clone stably overexpressing cytochrome P450 (CYP) 2C9.BMC research notes · 2026Article
- The HepG2 Cell Line as a Model for Studying Metabolic Dysfunction-Associated Steatotic Liver Disease.International journal of molecular sciences · 2026Review
- A microscopic investigation on insulin uptake in human hepatocellular carcinoma-derived HepG2 cells.RSC advances · 2025Article
- Mechanistic study of pexidartinib-induced toxicity in human hepatic cells.Chemico-biological interactions · 2025Article
- Advancing hepatotoxicity assessment: current advances and future directions.Toxicological research · 2025Review
- A Review on New Frontiers in Drug-Drug Interaction Predictions and Safety Evaluations with In Vitro Cellular Models.Pharmaceutics · 2025Review
- 7-Hydroxycannabidiol and 7-carboxycannabidiol induced cytotoxicity via apoptosis and endoplasmic reticulum stress in human hepatic cells.Archives of toxicology · 2025Article
- In vitro localization of modified zinc oxide nanoparticles showing selective anticancer effects against colorectal carcinoma using biophysical techniques.Scientific reports · 2025Article
- Cytochrome P450 2E1 aggravates DXR-induced myocardial injury through imbalanced mitochondrial OPA1.Cell communication and signaling : CCS · 2025Article
- Mixed Ru(II)-Ir(III) Complexes as Photoactive Inhibitors of the Major Human Drug Metabolizing Enzyme CYP3A4.Inorganic chemistry · 2024Article
- The Remarkable and Selective In Vitro Cytotoxicity of Synthesized Bola-Amphiphilic Nanovesicles on Etoposide-Sensitive and -Resistant Neuroblastoma Cells.Nanomaterials (Basel, Switzerland) · 2024Article
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- Hybrid non-animal modeling: A mechanistic approach to predict chemical hepatotoxicity.Journal of hazardous materials · 2024Article
- Sertraline induced acute hepatocellular liver injury in patient with major depressive disorder: a case report.Frontiers in psychiatry · 2024Article
- Exploring the hepatoprotective properties of citronellol:Open life sciences · 2024Article
- Efficacy of Novel Quaternary Ammonium and Phosphonium Salts Differing in Cation Type and Alkyl Chain Length against Antibiotic-ResistantInternational journal of molecular sciences · 2023Article
- The involvement of hepatic cytochrome P450s in the cytotoxicity of lapatinib.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- Article
- Dynamic Ir(III) Photosensors for the Major Human Drug-Metabolizing Enzyme Cytochrome P450 3A4.Inorganic chemistry · 2023Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The generation of reactive metabolites from therapeutic agents is one of the major mechanisms of drug-induced liver injury (DILI). In order to evaluate metabolism-related toxicity and improve drug efficacy and safety, we generated a battery of HepG2-derived cell lines that express 14 cytochrome P450s (CYPs) (1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 3A4, 3A5 and 3A7) individually using a lentiviral expression system. The expression/production of a specific CYP in each cell line was confirmed by an increased abundance of the CYP at both mRNA and protein levels. Moreover, the enzymatic activities of representative CYPs in the corresponding cell lines were also measured. Using our CYP-expressed HepG2 cells, the toxicity of three drugs that could induce DILI (amiodarone, chlorpromazine and primaquine) was assessed, and all of them showed altered (increased or decreased) toxicity compared to the toxicity in drug-treated wild-type HepG2 cells. CYP-mediated drug toxicity examined in our cell system is consistent with previous reports, demonstrating the potential of these cells for assessing metabolism-related drug toxicity. This cell system provides a practical in vitro approach for drug metabolism screening and for early detection of drug toxicity. It is also a surrogate enzyme source for the enzymatic characterization of a particular CYP that contributes to drug-induced liver toxicity.
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