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Amiodarone but not propafenone impairs bioenergetics and autophagy of human myocardial cells

dc.contributor.authorKrajčová, Adéla
dc.contributor.authorNěmcová, Vlasta
dc.contributor.authorHalačová, Milada
dc.contributor.authorWaldauf, Petr
dc.contributor.authorBalík, Martin
dc.contributor.authorDuška, František
dc.date.accessioned2024-09-27T13:45:43Z
dc.date.available2024-09-27T13:45:43Z
dc.date.issued2023
dc.identifier.urihttps://hdl.handle.net/20.500.14178/2631
dc.description.abstractCardiac and extra-cardiac side effects of common antiarrhythmic agents might be related to drug-induced mitochondrial dysfunction. Supratherapeutic doses of amiodarone have been shown to impair mitochondria in animal studies, whilst influence of propafenone on cellular bioenergetics is unknown. We aimed to assess effects of protracted exposure to pharmacologically relevant doses of amiodarone and propafenone on cellular bioenergetics and mitochondrial biology of human and mouse cardiomyocytes. In this study, HL-1 mouse atrial cardiomyocytes and primary human cardiomyocytes derived from the ventricles of the adult heart were exposed to 2 and 7 μg/mL of either amiodarone or propafenone. After 24 h, extracellular flux analysis and confocal laser scanning microscopy were used to measure mitochondrial functions. Autophagy was assessed by western blots and live-cell imaging of lysosomes. In human cardiomyocytes, amiodarone significantly reduced mitochondrial membrane potential and ATP production, in association with an inhibition of fatty acid oxidation and impaired complex I- and II-linked respiration in the electron transport chain. Expectedly, this led to increased anaerobic glycolysis. Amiodarone increased the production of reactive oxygen species and autophagy was also markedly affected. In contrast, propafenone-exposed cardiomyocytes did not exert any impairment of cellular bioenergetics. Similar changes after amiodarone treatment were observed during identical experiments performed on HL-1 mouse cardiomyocytes, suggesting a comparable pharmacodynamics of amiodarone among mammalian species. In conclusion, amiodarone but not propafenone in near-therapeutic concentrations causes a pattern of mitochondrial dysfunction with affected autophagy and metabolic switch from oxidative metabolism to anaerobic glycolysis in human cardiomyocytes.en
dc.language.isoen
dc.relation.urlhttps://doi.org/10.1016/j.taap.2023.116676
dc.rightsCreative Commons Uveďte původ 4.0 Internationalcs
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.titleAmiodarone but not propafenone impairs bioenergetics and autophagy of human myocardial cellsen
dcterms.accessRightsopenAccess
dcterms.licensehttps://creativecommons.org/licenses/by/4.0/legalcode
dc.date.updated2024-09-27T13:45:43Z
dc.subject.keywordAmiodaroneen
dc.subject.keywordCardiac cellsen
dc.subject.keywordEnergy metabolismen
dc.subject.keywordMitochondriaen
dc.subject.keywordPropafenoneen
dc.identifier.eissn1096-0333
dc.relation.fundingReferenceinfo:eu-repo/grantAgreement/MZ0/NU/NU21J-06-00078
dc.relation.fundingReferenceinfo:eu-repo/grantAgreement/MZ0/NV/NV18-06-00417
dc.relation.fundingReferenceinfo:eu-repo/grantAgreement/MSM//LX22NPO5104
dc.relation.fundingReferenceinfo:eu-repo/grantAgreement/UK/I-UK/I-2LF
dc.date.embargoStartDate2024-09-27
dc.type.obd73
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1016/j.taap.2023.116676
dc.identifier.utWos001079833400001
dc.identifier.eidScopus2-s2.0-85171462577
dc.identifier.obd634891
dc.identifier.rivRIV/00216208:11120/23:43925999
dc.identifier.rivRIV/00064165:_____/23:10467231
dc.identifier.rivRIV/00216208:11110/23:10467231
dc.identifier.rivRIV/00216208:11130/23:10467231
dc.identifier.pubmed37661063
dc.subject.rivPrimary30000::30200::30223
dc.subject.rivSecondary30000::30100::30104
dcterms.isPartOf.nameToxicology and Applied Pharmacology
dcterms.isPartOf.issn0041-008X
dcterms.isPartOf.journalYear2023
dcterms.isPartOf.journalVolume477
dcterms.isPartOf.journalIssueOctober
uk.faculty.primaryId109
uk.faculty.primaryName2. lékařská fakultacs
uk.faculty.primaryNameSecond Faculty of Medicineen
uk.faculty.secondaryId108
uk.faculty.secondaryId110
uk.faculty.secondaryId53
uk.faculty.secondaryName1. lékařská fakultacs
uk.faculty.secondaryNameFirst Faculty of Medicineen
uk.faculty.secondaryName3. lékařská fakultacs
uk.faculty.secondaryNameThird Faculty of Medicineen
uk.faculty.secondaryNameVšeobecná fakultní nemocnice v Prazecs
uk.faculty.secondaryNameVšeobecná fakultní nemocnice v Prazeen
uk.department.primaryId109
uk.department.primaryName2. lékařská fakultacs
uk.department.primaryNameSecond Faculty of Medicineen
uk.department.secondaryId1689
uk.department.secondaryId1521
uk.department.secondaryId5000002602
uk.department.secondaryId624
uk.department.secondaryId576
uk.department.secondaryNameÚstav farmakologiecs
uk.department.secondaryNameÚstav farmakologieen
uk.department.secondaryNameKlinika anesteziologie, resuscitace a intenzivní medicíny 1. LF UK a VFNcs
uk.department.secondaryNameDepartment of Anesthesiology and Intensive Care Medicineen
uk.department.secondaryNameKlinika anesteziologie, resuscitace a intenzivní medicíny 1.LF a VFNcs
uk.department.secondaryNameKlinika anesteziologie, resuscitace a intenzivní medicíny 1.LF a VFNen
uk.department.secondaryNameKlinika anesteziologie a resuscitace 3. LF UK a FNKVcs
uk.department.secondaryNameDepartment of Anaesthesia and Intensive Care Medicine 3FM CU and UHKVen
uk.department.secondaryNameÚstav biochemie, buněčné a molekulární biologie 3. LF UKcs
uk.department.secondaryNameDepartment of Biochemistry, Cell and Molecular Biology 3FM CUen
dc.type.obdHierarchyCsČLÁNEK V ČASOPISU::článek v časopisu::původní článekcs
dc.type.obdHierarchyEnJOURNAL ARTICLE::journal article::original articleen
dc.type.obdHierarchyCode73::152::206en
uk.displayTitleAmiodarone but not propafenone impairs bioenergetics and autophagy of human myocardial cellsen


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