{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T18:07:30Z","timestamp":1789150050885,"version":"build-2803163510"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["PG\/22\/10899"],"award-info":[{"award-number":["PG\/22\/10899"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Malaria is a global public health problem, causing significant morbidity and mortality, particularly in low and middle-income countries (LMICs). While mass drug administration (MDA) programs are central to elimination efforts, their effectiveness is limited by concerns over cardiotoxicity, resistance, and potential impacts on mitochondrial function. This study investigates the acute and prolonged effects of single and combination anti-malarial drugs on mitochondrial respiration in atrial cardiomyocytes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Human iPSC-derived atrial cardiomyocytes were treated with either single or combination anti-malarial drugs. Mitochondrial respiration was assessed using an extracellular flux analyser (Agilent Seahorse).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Treatment with mefloquine (MFQ) and its combinations reduced mitochondrial respiration, indicating impaired energy generation in cardiomyocytes. Prolonged exposure to halofantrine (HFN) significantly reduced maximal respiration and spare respiratory capacity, demonstrating compromised mitochondrial function. In contrast, acute and prolonged exposure to amodiaquine (AMD), artemether (ART), chloroquine (CQ), and piperaquine (PPQ) maintained mitochondrial function. While acute exposure to Ivermectin (IVM), an anti-parasitic drug used in malaria treatment programmes, did not affect mitochondrial health, prolonged exposure resulted in reduced coupling efficiency.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings provide insights into the effects of anti-malarial drugs on mitochondrial function in cardiomyocytes. Further studies should aim to elucidate the molecular mechanisms underlying these drug-induced mitochondrial effects.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0351511","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T17:22:05Z","timestamp":1789147325000},"page":"e0351511","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Acute and prolonged effects of anti-malarial drugs on mitochondrial respiration in atrial cardiomyocytes for cardiac safety evaluation"],"prefix":"10.1371","volume":"21","author":[{"given":"Rahme Nese","family":"Safakli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bonn","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karan 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