ArticleBiochemical pharmacology2011
Amiodarone impairs trafficking through late endosomes inducing a Niemann-Pick C-like phenotype.
Article in Biochemical pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 57 citations in OpenAlex.
- Extracellular Vesicles in Cardiovascular Disease: Intercellular Signaling, Liquid Biopsy Biomarkers, and Therapeutic Translation.Circulation research · 2026Review
- Contradictory Effects on Hepatocytes in ASMD.International journal of molecular sciences · 2026Review
- Niemann-Pick type C1 protein regulates epidermal growth factor receptor stability in hepatic cells and facilitates the early steps of Hepatitis B virus infection.Frontiers in cellular and infection microbiology · 2026Article
- The antiarrhythmic drugs amiodarone and dronedarone inhibit intoxication of cells with pertussis toxin.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Article
- Autophagy, innate immunity, and cardiac disease.Frontiers in cell and developmental biology · 2023Review
- Resolution of Sickle Cell Crisis Following Administration of Amiodarone.European journal of case reports in internal medicine · 2023Article
- Animal models of drug-induced pulmonary fibrosis: an overview of molecular mechanisms and characteristics.Cell biology and toxicology · 2022Review
- Amiodarone improves anemia in a murine model of sickle cell disease and is associated with increased erythrocyte bis(monoacylglycerol) phosphate.Scientific reports · 2022Article
- Regulation of exosome release by lysosomal acid ceramidase in coronary arterial endothelial cells: Role of TRPML1 channel.Current topics in membranes · 2022Article
- Drug-Induced Lysosomal Impairment Is Associated with the Release of Extracellular Vesicles Carrying Autophagy Markers.International journal of molecular sciences · 2021Article
- Pharmacokinetic Disposition of Amiodarone When Given with an Intralipid Rescue Strategy.Pharmaceutics · 2021Article
- Molecular Dynamic Simulation Search for Possible Amphiphilic Drug Discovery for Covid-19.Molecules (Basel, Switzerland) · 2021Article
- Lysosomal TRPML1 Channel: Implications in Cardiovascular and Kidney Diseases.Advances in experimental medicine and biology · 2021Article
- Potential COVID-19 therapeutics from a rare disease: weaponizing lipid dysregulation to combat viral infectivity.Journal of lipid research · 2020Review
- Amiodarone Alters Cholesterol Biosynthesis through Tissue-Dependent Inhibition of Emopamil Binding Protein and Dehydrocholesterol Reductase 24.ACS chemical neuroscience · 2020Article
- Arterial Medial Calcification through Enhanced small Extracellular Vesicle Release in Smooth Muscle-Specific Asah1 Gene Knockout Mice.Scientific reports · 2020Article
- Reversal of Endothelial Extracellular Vesicle-Induced Smooth Muscle Phenotype Transition by Hypercholesterolemia Stimulation: Role of NLRP3 Inflammasome Activation.Frontiers in cell and developmental biology · 2020Article
- Endothelial acid ceramidase in exosome-mediated release of NLRP3 inflammasome products during hyperglycemia: Evidence from endothelium-specific deletion of Asah1 gene.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2019Article
- Control of lysosomal TRPML1 channel activity and exosome release by acid ceramidase in mouse podocytes.American journal of physiology. Cell physiology · 2019Article
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Patients treated with amiodarone accumulate lysobisphosphatidic acid (LBPA), also known as bis(monoacylglycero)phosphate, in airway secretions and develop in different tissues vacuoles and inclusion bodies thought to originate from endosomes. To clarify the origin of these changes, we studied in vitro the effects of amiodarone on endosomal activities like transferrin recycling, Shiga toxin processing, ESCRT-dependent lentivirus budding, fluid phase endocytosis, proteolysis and exosome secretion. Furthermore, since the accumulation of LBPA might point to a broader disturbance in lipid homeostasis, we studied the effect of amiodarone on the distribution of LBPA, unesterified cholesterol, sphingomyelin and glycosphyngolipids. Amiodarone analogues were also studied, including the recently developed derivative dronedarone. We found that amiodarone does not affect early endosomal activities, like transferrin recycling, Shiga toxin processing and lentivirus budding. Amiodarone, instead, interferes with late compartments of the endocytic pathway, blocking the progression of fluid phase endocytosis and causing fusion of organelles, collapse of lumenal structures, accumulation of undegraded substrates and amassing of different types of lipids. Not all late endocytic compartments are affected, since exosome secretion is spared. These changes recall the Niemann-Pick type-C phenotype (NPC), but originate by a different mechanism, since, differently from NPC, they are not alleviated by cholesterol removal. Studies with analogues indicate that basic pKa and high water-solubility at acidic pH are crucial requirements for the interference with late endosomes/lysosomes and that, in this respect, dronedarone is at least as potent as amiodarone. These findings may have relevance in fields unrelated to rhythm control.
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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.