Doxorubicin-induced cardiotoxicity: An update on the molecular mechanism and novel therapeutic strategies for effective management

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dc.contributor.authorRawat, Pushkar Singh
dc.contributor.authorJaiswal, Aiswarya
dc.contributor.authorKhurana, Amit
dc.contributor.authorBhatti, Jasvinder Singh
dc.contributor.authorNavik, Umashanker
dc.date.accessioned2024-01-21T10:54:00Z
dc.date.accessioned2024-08-14T07:40:46Z
dc.date.available2024-01-21T10:54:00Z
dc.date.available2024-08-14T07:40:46Z
dc.date.issued2021-05-13T00:00:00
dc.description.abstractDoxorubicin (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 Ca2+ 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-1?), 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. � 2021 The Authorsen_US
dc.identifier.doi10.1016/j.biopha.2021.111708
dc.identifier.issn7533322
dc.identifier.urihttp://10.2.3.109/handle/32116/4183
dc.identifier.urlhttps://linkinghub.elsevier.com/retrieve/pii/S075333222100490X
dc.language.isoen_USen_US
dc.publisherElsevier Masson s.r.l.en_US
dc.subjectCardiotoxicityen_US
dc.subjectDNMT 1en_US
dc.subjectDoxorubicinen_US
dc.subjectHistone deacetylaseen_US
dc.subjectmicro RNAsen_US
dc.subjectOxidative stressen_US
dc.titleDoxorubicin-induced cardiotoxicity: An update on the molecular mechanism and novel therapeutic strategies for effective managementen_US
dc.title.journalBiomedicine and Pharmacotherapyen_US
dc.typeReviewen_US
dc.type.accesstypeOpen Accessen_US

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