Cardiotoxicity

Cardiotoxicity is one of the most encountered adverse effects observed alongside the therapeutic use of doxorubicin (DOX), thus curbing its therapeutic utility. Doxorubicin (DOX) is an anthracycline antibiotic used for the therapeutic management of several cancers, such as leukemia, soft-tissue sarcoma, and lymphoma. In spite of its effectiveness, its irreversible and dose-dependent cardiotoxicity limits its clinical application. The exact mechanisms of DOX-induced myocardial injury and cardiotoxicity remain elusive; therefore, preventing its severe side effects on patients is difficult.

Signaling Pathways:

In response to Doxorubicin treatment, activation of several protein kinases, neuregulin/ErbB2 signaling, and transcriptional factors modify mitochondrial functions that determine cell death or survival through the modulation of mitochondrial membrane permeability.

Induction of cardiotoxicity:

A single intraperitoneal (i.p.) dose (25 mg/kg) of DOX is administered to mice for 72 h.

OR

Rats receive an overall dose of DOX (21 mg/kg/rat) administered for 21 days at 3.5 mg/kg I.P. twice weekly for 21 days.