{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T21:11:00Z","timestamp":1781730660909,"version":"3.54.5"},"reference-count":57,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T00:00:00Z","timestamp":1635465600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Amiodarone is a potent antiarrhythmic drug and displays substantial liver toxicity in humans. It has previously been demonstrated that amiodarone and its metabolite (desethylamiodarone, DEA) can inhibit mitochondrial function, particularly complexes I (CI) and II (CII) of the electron transport system in various animal tissues and cell types. The present study, performed in human peripheral blood cells, and one liver-derived human cell line, is primarily aimed at assessing the concentration-dependent effects of these drugs on mitochondrial function (respiration and cellular ATP levels). Furthermore, we explore the efficacy of a novel cell-permeable succinate prodrug in alleviating the drug-induced acute mitochondrial dysfunction. Amiodarone and DEA elicit a concentration-dependent impairment of mitochondrial respiration in both intact and permeabilized platelets via the inhibition of both CI- and CII-supported respiration. The inhibitory effect seen in human platelets is also confirmed in mononuclear cells (PBMCs) and HepG2 cells. Additionally, amiodarone elicits a severe concentration-dependent ATP depletion in PBMCs, which cannot be explained solely by mitochondrial inhibition. The succinate prodrug NV118 alleviates the respiratory deficit in platelets and HepG2 cells acutely exposed to amiodarone. In conclusion, amiodarone severely inhibits metabolism in primary human mitochondria, which can be counteracted by increasing mitochondrial function using intracellular delivery of succinate.<\/jats:p>","DOI":"10.3390\/ijms222111786","type":"journal-article","created":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T22:21:34Z","timestamp":1635805294000},"page":"11786","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Cell-Permeable Succinate Rescues Mitochondrial Respiration in Cellular Models of Amiodarone Toxicity"],"prefix":"10.3390","volume":"22","author":[{"given":"Alina M.","family":"Be\u021biu","sequence":"first","affiliation":[{"name":"Department of Functional Sciences-Pathophysiology, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, Eftimie Murgu Sq. no. 2, 300041 Timi\u0219oara, Romania"},{"name":"Centre for Translational Research and Systems Medicine, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, Eftimie Murgu Sq. no. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6919-585X","authenticated-orcid":false,"given":"Imen","family":"Chamkha","sequence":"additional","affiliation":[{"name":"Mitochondrial Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, BMC A13, 221 84 Lund, Sweden"},{"name":"Abliva AB, Medicon Village, 223 81 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Gustafsson","sequence":"additional","affiliation":[{"name":"Mitochondrial Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, BMC A13, 221 84 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elna","family":"Meijer","sequence":"additional","affiliation":[{"name":"Mitochondrial Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, BMC A13, 221 84 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vlad F.","family":"Avram","sequence":"additional","affiliation":[{"name":"Centre for Translational Research and Systems Medicine, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, Eftimie Murgu Sq. no. 2, 300041 Timi\u0219oara, Romania"},{"name":"Department of Internal Medicine-Diabetes, Nutrition, Metabolic Diseases and Rheumatology, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, Eftimie Murgu Sq. no. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonor","family":"\u00c5sander Frostner","sequence":"additional","affiliation":[{"name":"Mitochondrial Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, BMC A13, 221 84 Lund, Sweden"},{"name":"Abliva AB, Medicon Village, 223 81 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2417-5767","authenticated-orcid":false,"given":"Johannes K.","family":"Ehinger","sequence":"additional","affiliation":[{"name":"Mitochondrial Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, BMC A13, 221 84 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucian","family":"Petrescu","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Diseases, Doctoral School of \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, Eftimie Murgu Sq. no. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danina M.","family":"Muntean","sequence":"additional","affiliation":[{"name":"Department of Functional Sciences-Pathophysiology, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, Eftimie Murgu Sq. no. 2, 300041 Timi\u0219oara, Romania"},{"name":"Centre for Translational Research and Systems Medicine, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, Eftimie Murgu Sq. no. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7901-1826","authenticated-orcid":false,"given":"Eskil","family":"Elm\u00e9r","sequence":"additional","affiliation":[{"name":"Mitochondrial Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, BMC A13, 221 84 Lund, Sweden"},{"name":"Abliva AB, Medicon Village, 223 81 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1007\/s12013-015-0626-4","article-title":"Cardiac Arrhythmias: Diagnosis, Symptoms, and Treatments","volume":"73","author":"Fu","year":"2015","journal-title":"Cell Biochem. 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