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Doxorubicin is a commonly used antitumor drug for the treatment of various cancers. However, its clinical application is greatly restricted by its severe cardiotoxicity. At present, doxorubicin-induced cardiotoxicity is categorized into acute and chronic forms, depending on the dosage and duration of exposure, which may eventually lead to the occurrence of heart failure. The pathogenesis of doxorubicin cardiotoxicity is associated with oxidative stress, mitochondrial damage, calcium overload, dysregulation of autophagy, and apoptosis. In forensic medical practice, cases of poisoning or even cardiac death caused by doxorubicin showed no obvious changes in cardiac morphology through routine forensic pathological examinations. The paper aims to summarize the research on the mechanisms of action of doxorubicin-induced cardiotoxicity in recent years, analyze and discuss the possible pathways of cardiomyocyte injury caused by doxorubicin, and provide references for research on the mechanisms of doxorubicin-induced cardiotoxicity and forensic application.
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http://dx.doi.org/10.12116/j.issn.1004-5619.2024.440404 | DOI Listing |
Phytomedicine
September 2025
Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China; Heart Center of Zhujiang Hospital, Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Guangzhou, Guangdong, China; Heart
Background: Impaired autophagic flux is an essential contributor to doxorubicin (DOX)-induced cardiotoxicity (DIC). TFEB is recognized as a key regulator of DOX-induced autolysosome accumulation; however, the mechanisms by which DOX suppresses TFEB expression remain unclear. 20-Deoxyingenol (20-DOI) is a small-molecule compound whose potential protective effects against DIC has not yet been elucidated.
View Article and Find Full Text PDFRedox Biol
September 2025
National Clinical Research Center for Geriatric Diseases, The Second Medical Center, Chinese PLA General Hospital, 100853, Beijing, China; Institute of Geriatric Medicine, The Second Medical Center, Chinese PLA General Hospital, 100853, Beijing, China.
Small extracellular vesicles (sEVs) critically orchestrate inter-tissue and inter-organ communications and may play essential roles in heart-tumor interaction. However, whether cancer-secreted sEVs affect the progression of doxorubicin-induced cardiotoxicity (DOXIC) via orchestrating the tumor cell-cardiomyocyte crosstalk has not yet been explored. Herein, we reveal that Doxorubicin (DOX)-treated breast cancer cells secrete sEVs (D-BCC-sEVs) that exacerbate DOX-induced ferroptosis of human iPSC-derived cardiomyocytes (hiCMs).
View Article and Find Full Text PDFInt J Mol Med
November 2025
Department of Anesthesiology, Chongqing Traditional Chinese Medicine Hospital, Chongqing 400021, P.R. China.
Doxorubicin (DOX)‑induced cardiotoxicity (DIC) remains a critical challenge in cancer therapy, significantly limiting its use in clinical practice. The underlying mechanisms involve disruptions in cardiac metabolism and mitochondrial dysfunction. The heart relies on mitochondrial oxidative phosphorylation to produce ATP, which is essential for maintaining both contraction and relaxation.
View Article and Find Full Text PDFCirc Heart Fail
September 2025
Department of Cardiology, Center for Translational Medicine, Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. (J.W., K.L., Y.Y., X.X., T.X., H.X., H.Z., T.D., Y.L., C.L., X.L., Y.D., J.-S.O., Y.C., Z.-P.H.).
Background: Doxorubicin (DOX) cardiotoxicity increases cardiovascular risk in cancer patients, mainly through mitochondrial damage. However, the underlying mechanisms remain unclear, and whether mitochondrial short open reading frame-encoded peptides can mitigate DOX-induced cardiotoxicity is unknown.
Methods: Five adeno-associated viruses expressing mitochondrial short open reading frame-encoded peptides under the cardiac troponin T promoter, including MODICA (mito-SEP protector against DOX-induced cardiac injury), were screened in a DOX-induced cardiotoxicity mouse model (n=3-5 per group).
Daru
September 2025
College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj, Kingdom of Saudi Arabia.
Background: Doxorubicin (Dox) is a chemotherapy medication used in the therapy of cancers. However, despite its killing of cancer cells, Dox is toxic to the heart and can lead to heart failure. This outcome in turn poses a therapeutic challenge given the limited treatment options available to these individuals.
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