ArticlePLoS computational biology2016
A Biophysical Systems Approach to Identifying the Pathways of Acute and Chronic Doxorubicin Mitochondrial Cardiotoxicity.
Article in PLoS computational biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- Cardiac remodelling in type 2 diabetes: Pathophysiological mechanisms and opportunities for multiscale computational modelling and simulation.The Journal of physiology · 2026Review
- Anthracycline-induced cardiorenal toxicity: from molecular mechanisms to clinical management.Frontiers in cardiovascular medicine · 2026Review
- The multifaceted mechanisms of Tanshinone IIA in doxorubicin-induced cardiotoxicity.Frontiers in medicine · 2026Review
- A narrative review of therapy-induced senescence in cancer: mechanisms, immune interplay, and therapeutic opportunities.Journal of the Egyptian National Cancer Institute · 2025Review
- Temporal analysis of doxorubicin-induced cardiac toxicity and hypertrophy.NPJ systems biology and applications · 2025Article
- Understanding the Mechanisms of Chemotherapy-Related Cardiotoxicity Employing hiPSC-Derived Cardiomyocyte Models for Drug Screening and the Identification of Genetic and Epigenetic Variants.International journal of molecular sciences · 2025Review
- Evolution of Theories on Doxorubicin-Induced Late Cardiotoxicity-Role of Topoisomerase.International journal of molecular sciences · 2024Review
- Carvedilol Phenocopies PGC-1α Overexpression to Alleviate Oxidative Stress, Mitochondrial Dysfunction and Prevent Doxorubicin-Induced Toxicity in Human iPSC-Derived Cardiomyocytes.Antioxidants (Basel, Switzerland) · 2023Article
- Role of oxidative stress and inflammation-related signaling pathways in doxorubicin-induced cardiomyopathy.Cell communication and signaling : CCS · 2023Review
- Kinetic Mathematical Modeling of Oxidative Phosphorylation in Cardiomyocyte Mitochondria.Cells · 2022Review
- Review
- The Role of Flavonoids as a Cardioprotective Strategy against Doxorubicin-Induced Cardiotoxicity: A Review.Molecules (Basel, Switzerland) · 2022Review
- Cancer Therapy-Induced Cardiotoxicity-A Metabolic Perspective on Pathogenesis, Diagnosis and Therapy.International journal of molecular sciences · 2021Review
- The Effects of Bergamot Polyphenolic Fraction,Nutrients · 2021Article
- Network integration and modelling of dynamic drug responses at multi-omics levels.Communications biology · 2020Article
- Balance of Active, Passive, and Anatomical Cardiac Properties in Doxorubicin-Induced Heart Failure.Biophysical journal · 2019Article
- Use of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Preclinical Cancer Drug Cardiotoxicity Testing: A Scientific Statement From the American Heart Association.Circulation research · 2019Review
- Cardiac Troponins are Among Targets of Doxorubicin-Induced Cardiotoxicity in hiPCS-CMs.International journal of molecular sciences · 2019Article
- Computational models in cardiology.Nature reviews. Cardiology · 2019Review
- Peroxisomes contribute to oxidative stress in neurons during doxorubicin-based chemotherapy.Molecular and cellular neurosciences · 2018Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The clinical use of the anthracycline doxorubicin is limited by its cardiotoxicity which is associated with mitochondrial dysfunction. Redox cycling, mitochondrial DNA damage and electron transport chain inhibition have been identified as potential mechanisms of toxicity. However, the relative roles of each of these proposed mechanisms are still not fully understood. The purpose of this study is to identify which of these pathways independently or in combination are responsible for doxorubicin toxicity. A state of the art mathematical model of the mitochondria including the citric acid cycle, electron transport chain and ROS production and scavenging systems was extended by incorporating a novel representation for mitochondrial DNA damage and repair. In silico experiments were performed to quantify the contributions of each of the toxicity mechanisms to mitochondrial dysfunction during the acute and chronic stages of toxicity. Simulations predict that redox cycling has a minor role in doxorubicin cardiotoxicity. Electron transport chain inhibition is the main pathway for acute toxicity for supratherapeutic doses, being lethal at mitochondrial concentrations higher than 200μM. Direct mitochondrial DNA damage is the principal pathway of chronic cardiotoxicity for therapeutic doses, leading to a progressive and irreversible long term mitochondrial dysfunction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.