{
  "abstract": "Objectives: 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. Methods: 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). Results: 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. Conclusions: 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.",
  "abstract_shown": true,
  "affiliations": [
    "Faculty of Health and Medical Science, School of Veterinary Medicine, University of Surrey, Guildford, United Kingdom",
    "Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom",
    "Homerton College, University of Cambridge, Cambridge, United Kingdom",
    "Royal Free London NHS Foundation Trust, London, United Kingdom",
    "Department of Physiology, Development and Neuroscience, Downing Site, University of Cambridge, Cambridge, United Kingdom",
    "Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom",
    "National Heart & Lung Institute, Imperial College London, London, United Kingdom",
    "School of Nursing and Health Sciences, Hong Kong Metropolitan University, Hong KongChina"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Rahme Nese Safakli"
    },
    {
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        1
      ],
      "name": "Bonn Lee"
    },
    {
      "affs": [
        2
      ],
      "name": "Karan R. Chadda"
    },
    {
      "affs": [
        3
      ],
      "name": "Savithri Sathivelu"
    },
    {
      "affs": [
        4
      ],
      "name": "Ioannis Smyrnias"
    },
    {
      "affs": [
        5
      ],
      "name": "Christopher L.H. Huang"
    },
    {
      "affs": [
        6
      ],
      "name": "Joel Tarning"
    },
    {
      "affs": [
        7
      ],
      "name": "Cesare Terracciano"
    },
    {
      "name": "Gary Tse"
    },
    {
      "name": "Charlotte E. Edling"
    },
    {
      "name": "Kamalan Jeevaratnam"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/anw3dea32zgce.bib",
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  "doi": "10.1371/journal.pone.0351511",
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  "id": "anw3dea32zgce",
  "issns": [
    "1932-6203"
  ],
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  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Mitochondrial Function and Pathology"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Biological tissue/Muscle tissue/Muscle cells/Cardiomyocytes"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Bioenergetics/Energy-producing organelles/Mitochondria"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular structures and organelles/Energy-producing organelles/Mitochondria"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Muscle cells/Cardiomyocytes"
    ],
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      "plos",
      "/Biology and life sciences/Physiology/Physiological processes/Respiration/Oxygen consumption"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Biological tissue/Muscle tissue/Muscle cells/Cardiomyocytes"
    ],
    [
      "plos",
      "/Medicine and health sciences/Medical conditions/Parasitic diseases"
    ],
    [
      "plos",
      "/Medicine and health sciences/Medical conditions/Parasitic diseases/Malaria"
    ],
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      "/Medicine and health sciences/Medical conditions/Tropical diseases/Malaria"
    ],
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      "plos",
      "/Medicine and health sciences/Pharmaceutics/Drug therapy"
    ],
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      "/Medicine and health sciences/Pharmacology/Drugs/Antimalarials"
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      "/Physical sciences/Physics/Nuclear physics/Nucleons/Protons"
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  "pdf_url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0351511&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-11",
  "publisher": "Public Library of Science",
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  "sources": [
    {
      "first_seen": "2026-10-30T12:17:56Z",
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  "subjects": [
    {
      "field": "biology",
      "origin": "plos:cell biology",
      "subfield": "cell-biology"
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    {
      "field": "medicine",
      "origin": "plos:anatomy",
      "subfield": "physiology"
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  "title": "Acute and prolonged effects of anti-malarial drugs on mitochondrial respiration in atrial cardiomyocytes for cardiac safety evaluation",
  "title_text": "Acute and prolonged effects of anti-malarial drugs on mitochondrial respiration in atrial cardiomyocytes for cardiac safety evaluation",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:56Z",
  "url": "https://research.draconitic.com/paper/anw3dea32zgce",
  "venue": "PLOS One",
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}