Sirtuin-3 Regulates the Mechanism of Doxorubicin-induced Cardiotoxicity

Abstract

Doxorubicin (DOX) is a widely used and efficacious anthracycline in clinical practice for the treatment of various tumors; however, a major limitation of DOX therapy is its cardiotoxicity, which significantly restricts its clinical application. Mitochondria in the heart are particularly susceptible to the deleterious effects of DOX, resulting in mitochondrial dysfunction, reactive oxygen species generation, cardiomyocyte apoptosis, bioenergetic failure, and impaired cardiac function. Mitochondrial sirtuins (SIRT3 and SIRT4) play pivotal roles in these cellular processes. Sirtuin-3 (SIRT3), a member of the mitochondrial Sirtuin family, effectively attenuates DOX-induced myocardial injury by suppressing inflammation and oxidative damage while improving mitochondrial function. Therefore, SIRT3 is a key regulator involved in multiple mechanisms underlying DOX-induced cardiotoxicity. Several studies have shown the protective effects of SIRT3 against DOX-induced myocardial injury and have provided insights into its potential for future clinical applications.