Doxorubicin-induced cardiotoxicity: An update on the molecular mechanism and novel therapeutic strategies for effective management
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homeostasis, autophagy, the release of nitric oxide and inflammatory mediators and altered gene and protein expression that involved apoptosis. Dox also causes downregulation of DNA methyltransferase 1 (DNMT1) enzyme activity which leads to a reduction in the DNA methylation process. This hypomethylation causes dysregulation in the mitochondrial genes like peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1-alpha (PGC-1α), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM) unit in the heart. Apart from DNA methylation, Dox treatment also alters the micro RNAs levels and histone deacetylase (HDAC) activity. Therefore, in the current review, we have provided a detailed update on the current understanding of the pathological mechanisms behind the well-known Dox-induced cardiotoxicity. Further, we have provided some of the most plausible pharmacological strategies which have been tested against Dox-induced cardiotoxicity.
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The cumulative anthracycline dose is a major risk factor for severe cardiomyopathy development, but young age at treatment, female sex, peak drug exposure and additional stress to the heart have also been implicated.
“The cumulative anthracycline dose is a major risk factor for severe cardiomyopathy development but young age at treatment, female sex, peak drug exposure and additional stress to the heart have also been implicated 161,162,163 .”
From Osteosarcoma (2022) · cites this paper as [163]
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- Authors
- Rawat, P. S., Jaiswal, A., Khurana, A., Bhatti, J. S., & Navik, U.
- Affiliations
- Central University of Punjab (IN)
- P.V. Narsimha Rao Telangana Veterinary University (IN)
- Venue
- Biomedicine & Pharmacotherapy
- Publisher
- Elsevier BV
- Published
- 2021-07
- Volume
- 139
- Pages
- 111708
- ISSN
- 0753-3322 (ISSN-L)
- OpenAlex
- W3160992829
- Cited by
- 909
- References
- 198
- Citations by year
- 2026: 171 · 2025: 232 · 2024: 208 · 2023: 193 · 2022: 92 · 2021: 13
- FWCI
- 24.68
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Biomedicine & Pharmacotherapy (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Royal Society of Medicine
- University of Central Punjab (GP-25)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Chemotherapy-induced cardiotoxicity and mitigation
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- doxorubicin, cardiotoxicity, molecular mechanisms, DNA methylation, DNMT1, mitochondrial dysfunction, PGC-1α, NRF1, TFAM, microRNA, histone deacetylase, autophagy, apoptosis, nitric oxide, inflammatory mediators, cardioprotection, anthracycline chemotherapy
- MeSH terms
- Animals, Antibiotics, Antineoplastic, Doxorubicin, Humans, Mitochondria, Heart, Apoptosis, Oxidative Stress, Cardiotoxicity
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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