Acute and prolonged effects of anti-malarial drugs on mitochondrial respiration in atrial cardiomyocytes for cardiac safety evaluation
8 affiliations
- 1Faculty of Health and Medical Science, School of Veterinary Medicine, University of Surrey, Guildford, United Kingdom
- 2Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom
- 3Homerton College, University of Cambridge, Cambridge, United Kingdom
- 4Royal Free London NHS Foundation Trust, London, United Kingdom
- 5Department of Physiology, Development and Neuroscience, Downing Site, University of Cambridge, Cambridge, United Kingdom
- 6Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
- 7National Heart & Lung Institute, Imperial College London, London, United Kingdom
- 8School of Nursing and Health Sciences, Hong Kong Metropolitan University, Hong KongChina
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.
Related
- AMPK reinforces mitochondrial metabolism and suppresses pathological remodeling in Complex V-deficient cardiomyocytes
- Exogenous L6 myotube mitochondrial transplantation attenuates hypertrophy and elicits a unique proteomic signature in phenylephrine-treated H9C2 cardiomyocytes
- Toxic Concentrations of Glutamate Induce Ferroptosis without Affecting Mitochondrial Respiration in Rodent Brain Slice Cultures
- Effect of Leucovorin on Mitochondrial Respiration and One-Carbon Metabolism in Autism Spectrum Disorder: A Double-Blind Placebo-Controlled Substudy
- PARP1/2-linked ADP-ribosylation impairs trophoblast mitochondrial respiration in a TNF-α model of inflammation-mediated preeclampsia.
BibTeX
@article{safakli2026acute,
title = {{Acute and prolonged effects of anti-malarial drugs on mitochondrial respiration in atrial cardiomyocytes for cardiac safety evaluation}},
author = {Rahme Nese Safakli and Bonn Lee and Karan R. Chadda and Savithri Sathivelu and Ioannis Smyrnias and Christopher L.H. Huang and Joel Tarning and Cesare Terracciano and Gary Tse and Charlotte E. Edling and Kamalan Jeevaratnam},
journal = {PLOS One},
year = {2026},
month = sep,
doi = {10.1371/journal.pone.0351511},
url = {https://doi.org/10.1371/journal.pone.0351511},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Acute and prolonged effects of anti-malarial drugs on mitochondrial respiration in atrial cardiomyocytes for cardiac safety evaluation
AU - Rahme Nese Safakli
AU - Bonn Lee
AU - Karan R. Chadda
AU - Savithri Sathivelu
AU - Ioannis Smyrnias
AU - Christopher L.H. Huang
AU - Joel Tarning
AU - Cesare Terracciano
AU - Gary Tse
AU - Charlotte E. Edling
AU - Kamalan Jeevaratnam
PY - 2026
DA - 2026/09/11
JO - PLOS One
DO - 10.1371/journal.pone.0351511
UR - https://doi.org/10.1371/journal.pone.0351511
AB - 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.
SN - 1932-6203
ER -