ArticleToxicology letters2016
The role of CYP 3A4 and 1A1 in amiodarone-induced hepatocellular toxicity.
Article in Toxicology letters, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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.
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Who cites it
19 citing papers in PubMed, 45 citations in OpenAlex.
- 7-Hydroxycannabidiol and 7-carboxycannabidiol induced cytotoxicity via apoptosis and endoplasmic reticulum stress in human hepatic cells.Archives of toxicology · 2025Article
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- The involvement of hepatic cytochrome P450s in the cytotoxicity of lapatinib.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
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- Clinical significance of the rivaroxaban-dronedarone interaction: insights from physiologically based pharmacokinetic modelling.European heart journal open · 2023Review
- Study of the roles of cytochrome P450 (CYPs) in the metabolism and cytotoxicity of perhexiline.Archives of toxicology · 2022Article
- Optimisation of the HepaRG cell line model for drug toxicity studies using two different cultivation conditions: advantages and limitations.Archives of toxicology · 2022Article
- Cell-Permeable Succinate Rescues Mitochondrial Respiration in Cellular Models of Amiodarone Toxicity.International journal of molecular sciences · 2021Article
- A mechanism of perhexiline's cytotoxicity in hepatic cells involves endoplasmic reticulum stress and p38 signaling pathway.Chemico-biological interactions · 2021Article
- Transcriptional Regulation of Drug Metabolizing CYP Enzymes by Proinflammatory Wnt5A Signaling in Human Coronary Artery Endothelial Cells.Frontiers in pharmacology · 2021Article
- Characterization of cytochrome P450s (CYP)-overexpressing HepG2 cells for assessing drug and chemical-induced liver toxicity.Journal of environmental science and health. Part C, Toxicology and carcinogenesis · 2021Article
- The role of hepatic cytochrome P450s in the cytotoxicity of sertraline.Archives of toxicology · 2020Article
- Development and Application of TK6-derived Cells Expressing Human Cytochrome P450s for Genotoxicity Testing.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- Emerging club drugs: 5-(2-aminopropyl)benzofuran (5-APB) is more toxic than its isomer 6-(2-aminopropyl)benzofuran (6-APB) in hepatocyte cellular models.Archives of toxicology · 2020Article
- Rapid maturation of the hepatic cell line Huh7 via CDK inhibition for PXR dependent CYP450 metabolism and induction.Scientific reports · 2019Article
- Influence of concomitant medication on plasma concentration of amiodarone in patients with atrial fibrillation - a pilot study.Medicine and pharmacy reports · 2019Article
- The role of hepatic cytochrome P450s in the cytotoxicity of dronedarone.Archives of toxicology · 2018Article
- Catechin and epicatechin reduce mitochondrial dysfunction and oxidative stress induced by amiodarone in human lung fibroblasts.Journal of arrhythmia · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Amiodarone is a widely used potent antiarrhythmic for the treatment of cardiac disease; however, its use is often discontinued due to numerous adverse effects, including hepatotoxicity. To investigate the role of drug metabolism in this liver toxicity, amiodarone and its major metabolite desethylamiodarone were incubated with HepG2 cells overexpressing a series of cytochrome P450 (CYP) isoforms. Significantly higher cytotoxicity of amiodarone was observed in HepG2 cells overexpressing CYP3A4 or CYP1A1, compared with that observed in empty vector transduced control cells. Further, higher levels of the more potent hepatotoxic metabolite desethylamiodarone were detected in CYP3A4 or CYP1A1 expressed cells. The CYP3A4 inhibitor ketoconazole and the CYP1A1 inhibitor α-naphthoflavone drastically inhibited the metabolism of amiodarone to desethylamiodarone. Along with the inhibition of CYP1A1 or CYP3A4, the cytotoxicity of amiodarone was significantly reduced. These data indicate that the metabolism of amiodarone to desethylamiodarone by CYP1A1 or CYP3A4 plays an important role in the hepatocellular toxicity of amiodarone.
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