ArticleThe Journal of clinical investigation2014
Cardiotoxicity of doxorubicin is mediated through mitochondrial iron accumulation.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 482 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
482 citing papers in PubMed, 1 synthesis or guideline pooled it, 867 citations in OpenAlex.
- Pharmacogenetics of chemotherapy treatment response and -toxicities in patients with osteosarcoma: a systematic review.BMC cancer · 2022Pooled it
- HydroMg attenuates doxorubicin-induced myocardial injury via promoting mitochondrial function.Medical gas research · 2027Article
- Mitochondrial Ferritin in Subclinical Anthracycline-Induced Cardiotoxicity in Humans: A Pilot Study.Journal of cardiovascular translational research · 2026Article
- Subcellular regulation of ferroptosis: roles of individual intracellular organelles and cross talk.American journal of physiology. Cell physiology · 2026Review
- Cardiovascular Toxicity in Cancer Therapy: Potential Mechanisms of Ferroptosis and Treatment Strategies.Cells · 2026Review
- Phosphatidylserine-based liposomes encapsulating DMX-5804 protect against doxorubicin-induced cardiotoxicity.RSC pharmaceutics · 2026Article
- Emerging Role of Ferroptosis in Chemotherapy-Associated Hepatorenal Toxicity: Mechanistic Insights and Toxicological Perspectives.ACS pharmacology & translational science · 2026Review
- Bidentate Metal-Binding Motifs in US FDA Approved Small Molecule Drugs.Journal of medicinal chemistry · 2026Review
- Mechanisms of Doxorubicin-Induced Cardiac Senescence and Potential Therapeutic Strategies.Biomolecules · 2026Review
- The Role of Metal Ions in Mitochondria: From Energy Metabolism to Cell Destiny.Biological trace element research · 2026Review
- Arctigenin discovered by high-throughput screening ameliorates doxorubicin-induced cardiotoxicity as a novel natural KEAP1-NRF2 inhibitor.Journal of pharmaceutical analysis · 2026Article
- Sotagliflozin ameliorates doxorubicin-induced cardiomyopathy by regulating inflammation and mitochondrial dysfunction through the AMPK/mTOR pathway.Experimental and therapeutic medicine · 2026Article
- Vardenafil Alleviates Doxorubicin-Induced Cardiotoxicity Associated with Restoration of the AMPK/SIRT1 Signaling Pathway.Biomedicines · 2026Article
- Dual-Metal Regulation of Cardiac Remodeling: Targeting the LOXL2-Ferroptosis Axis in Metal-Induced Cardiac Dysfunction.Cardiovascular toxicology · 2026Review
- Huashi Baidu formula may attenuate adriamycin-induced myocardial injury via modulating NRF2-ATF3-SRXN1 axis-mediated ferroptosis.Chinese herbal medicines · 2026Article
- Ivabradine as a Cardio-Protective Agent Against Anthracycline-Induced Cardiotoxicity: A Narrative Review.Cardiovascular drugs and therapy · 2026Review
- Metal-dependent regulated cell death: Molecular architecture and translational frontiers.iMeta · 2026Review
- Article
- Dapagliflozin Protects Cardiomyocytes against Doxorubicin-Induced Toxicity by Modulating Sirtuin 1/Sirtuin 3 and Ferroptosis Pathway.ACS pharmacology & translational science · 2026Article
- Ferroptosis in cardiovascular diseases: molecular mechanisms and a novel therapeutic target.Molecular biomedicine · 2026Review
422 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Doxorubicin is an effective anticancer drug with known cardiotoxic side effects. It has been hypothesized that doxorubicin-dependent cardiotoxicity occurs through ROS production and possibly cellular iron accumulation. Here, we found that cardiotoxicity develops through the preferential accumulation of iron inside the mitochondria following doxorubicin treatment. In isolated cardiomyocytes, doxorubicin became concentrated in the mitochondria and increased both mitochondrial iron and cellular ROS levels. Overexpression of ABCB8, a mitochondrial protein that facilitates iron export, in vitro and in the hearts of transgenic mice decreased mitochondrial iron and cellular ROS and protected against doxorubicin-induced cardiomyopathy. Dexrazoxane, a drug that attenuates doxorubicin-induced cardiotoxicity, decreased mitochondrial iron levels and reversed doxorubicin-induced cardiac damage. Finally, hearts from patients with doxorubicin-induced cardiomyopathy had markedly higher mitochondrial iron levels than hearts from patients with other types of cardiomyopathies or normal cardiac function. These results suggest that the cardiotoxic effects of doxorubicin develop from mitochondrial iron accumulation and that reducing mitochondrial iron levels protects against doxorubicin-induced cardiomyopathy.
Indexed as
Identifiers
What OpenQuestion holds
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.