ArticleMolecular and cellular biochemistry2016
Oxidative stress does not play a primary role in the toxicity induced with clinical doses of doxorubicin in myocardial H9c2 cells.
Article in Molecular and cellular biochemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- Endothelial progenitor cell susceptibility to DNA damaging and DDR-modulating compounds determines endothelial differentiation accuracy.Stem cell research & therapy · 2026Article
- Toxicological and anti-inflammatory activities of doxorubicin loaded onto pH-sensitive poly(β-amino ester) modified mesoporous silica nanoparticles in mice.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Cell death regulation in myocardial toxicity induced by antineoplastic drugs.Frontiers in cell and developmental biology · 2023Review
- Review
- Metabolic Conversion and Removal of Manganese Ferrite Nanoparticles in RAW264.7 Cells and Induced Alteration of Metal Transporter Gene Expression.International journal of nanomedicine · 2021Article
- The Prophylactic Effect of Pinocembrin Against Doxorubicin-Induced Cardiotoxicity in anFrontiers in pharmacology · 2020Article
- Molecular Mechanisms of Cardiomyocyte Death in Drug-Induced Cardiotoxicity.Frontiers in cell and developmental biology · 2020Review
- Embryonic stem cell-derived exosomes inhibit doxorubicin-induced TLR4-NLRP3-mediated cell death-pyroptosis.American journal of physiology. Heart and circulatory physiology · 2019Article
- Personalized medicine in cardio-oncology: the role of induced pluripotent stem cell.Cardiovascular research · 2019Review
- High Glucose Level Impairs Human Mature Bone Marrow Adipocyte Function Through Increased ROS Production.Frontiers in endocrinology · 2019Article
- A Personalized Model ofJournal of the American Society of Nephrology : JASN · 2017Article
- Doxorubicin induces cardiotoxicity through upregulation of death receptors mediated apoptosis in cardiomyocytes.Scientific reports · 2017Article
- Statins in anthracycline-induced cardiotoxicity: Rac and Rho, and the heartbreakers.Cell death & disease · 2017Review
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The implication of oxidative stress as primary mechanism inducing doxorubicin (DOX) cardiotoxicity is still questionable as many in vitro studies implied supra-clinical drug doses or unreliable methodologies for reactive oxygen species (ROS) detection. The aim of this study was to clarify whether oxidative stress is involved in compliance with the conditions of clinical use of DOX, and using reliable tools for ROS detection. We examined the cytotoxic mechanisms of 2 μM DOX 1 day after the beginning of the treatment in differentiated H9c2 rat embryonic cardiac cells. Cells were exposed for 2 or 24 h with DOX to mimic a single chronic dosage or to favor accumulation, respectively. We found that apoptosis was prevalent in cells exposed for a short period with DOX: cells showed typical hallmarks as loss of anchorage ability, mitochondrial hyperpolarization followed by the collapse of mitochondrial activity, and nuclear condensation. Increasing the exposure period favored a shift to necrosis as the cells preferentially exhibited early DNA impairment and nuclear swelling. In either case, measuring the fluorescence lifetime of 1-pyrenebutyric acid or the intensities of dihydroethidium or amplex red showed a consistent pattern in ROS production which was a slight increased level far from representative of an oxidative stress. Moreover, pre-treatment with dexrazoxane provided a cytoprotective effect although it failed to detoxify ROS. Our data support that oxidative stress is unlikely to be the primary mechanism of DOX cardiac toxicity in vitro.
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