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- W3160992829 startingPage "111708" @default.
- W3160992829 abstract "Doxorubicin (Dox) is a secondary metabolite of the mutated strain of Streptomyces peucetius var. Caesius and belongs to the anthracyclines family. The anti-cancer activity of Dox is mainly exerted through the DNA intercalation and inhibiting topoisomerase II enzyme in fast-proliferating tumors. However, Dox causes cumulative and dose-dependent cardiotoxicity, which results in increased risks of mortality among cancer patients and thus limiting its wide clinical applications. There are several mechanisms has been proposed for doxorubicin-induced cardiotoxicity and oxidative stress, free radical generation and apoptosis are most widely reported. Apart from this, other mechanisms are also involved in Dox-induced cardiotoxicity such as impaired mitochondrial function, a perturbation in iron regulatory protein, disruption of Ca 2+ 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. • Doxorubicin (Dox) belongs to the anthracyclines family. • Dox-induced cardiotoxicity involves multiple mechanisms. • Increased mortality risks limiting its wide clinical applications. • Pharmacological and phytochemical could reduce mortality among cancer patients." @default.
- W3160992829 created "2021-05-24" @default.
- W3160992829 creator A5042737050 @default.
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- W3160992829 creator A5083718300 @default.
- W3160992829 creator A5086069579 @default.
- W3160992829 date "2021-07-01" @default.
- W3160992829 modified "2023-10-14" @default.
- W3160992829 title "Doxorubicin-induced cardiotoxicity: An update on the molecular mechanism and novel therapeutic strategies for effective management" @default.
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