ArticleEnvironmental and molecular mutagenesis2018
DNA damage-induced apoptosis and mitogen-activated protein kinase pathway contribute to the toxicity of dronedarone in hepatic cells.
Article in Environmental and molecular mutagenesis, 2018. 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, 30 citations in OpenAlex.
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- 7-Hydroxycannabidiol and 7-carboxycannabidiol induced cytotoxicity via apoptosis and endoplasmic reticulum stress in human hepatic cells.Archives of toxicology · 2025Article
- Toxicity of cannabidiol and its metabolites in TM3 mouse Leydig cells: a comparison with primary human Leydig cells.Archives of toxicology · 2024Article
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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
- Induction of apoptosis by cannabidiol and its main metabolites in human Leydig cells.Archives of toxicology · 2023Article
- Study of the roles of cytochrome P450 (CYPs) in the metabolism and cytotoxicity of perhexiline.Archives of toxicology · 2022Article
- Mitochondrial Effects of Common Cardiovascular Medications: The Good, the Bad and the Mixed.International journal of molecular sciences · 2022Review
- In vitro effects of cannabidiol and its main metabolites in mouse and human Sertoli cells.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2022Article
- TOP2A inhibition reverses drug resistance of hepatocellular carcinoma to regorafenib.American journal of cancer research · 2022Article
- Tripterygium glycoside ameliorates neuroinflammation in a mouse model of Aβ25-35-induced Alzheimer's disease by inhibiting the phosphorylation of IκBα and p38.Bioengineered · 2021Article
- A mechanism of perhexiline's cytotoxicity in hepatic cells involves endoplasmic reticulum stress and p38 signaling pathway.Chemico-biological interactions · 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 Cytosolic DNA-Sensing cGAS-STING Pathway in Liver Diseases.Frontiers in cell and developmental biology · 2021Review
- Mitochondrial dysfunction and apoptosis underlie the hepatotoxicity of perhexiline.Toxicology in vitro : an international journal published in association with BIBRA · 2020Article
- The role of hepatic cytochrome P450s in the cytotoxicity of sertraline.Archives 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
- A Novel Tanshinone Analog Exerts Anti-Cancer Effects in Prostate Cancer by Inducing Cell Apoptosis, Arresting Cell Cycle at G2 Phase and Blocking Metastatic Ability.International journal of molecular sciences · 2019Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Dronedarone, an antiarrhythmic drug, has been marketed as an alternative to amiodarone. The use of dronedarone has been associated with severe liver injury; however, the mechanisms remain unclear. In this study, the possible mechanisms of dronedarone induced liver toxicity were characterized in HepG2 cells. Dronedarone decreased cells viability and induced apoptosis and DNA damage in a concentration- and time-dependent manner. Pretreatment of the HepG2 cells with apoptosis inhibitors (caspase-3, -8, and -9) or the necrosis inhibitor (Necrox-5), partially, but significantly, reduced the release of lactate dehydrogenase. Dronedarone caused the release of cytochrome c from mitochondria to cytosol, a prominent feature of apoptosis. In addition, the activation of caspase-2 was involved in dronedarone induced DNA damage and the activation of JNK and p38 signaling pathways. Inhibition of JNK and p38 by specific inhibitors attenuated dronedarone-induced cell death, apoptosis, and DNA damage. Additionally, suppression of caspase-2 decreased the activities of JNK and p38. Dronedarone triggered DNA damage was regulated by downregulation of topoisomerase IIα at both transcriptional and post-transcriptional levels. Taken together, our data show that DNA damage, apoptosis, and the activation of JNK and p38 contribute to dronedarone-induced cytotoxicity. Environ. Mol. Mutagen. 59:278-289, 2018. © 2018 Wiley Periodicals, Inc.
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