Doxorubicin induced cardio toxicity through sirtuins mediated mitochondrial disruption

The chemotherapeutic drug Doxorubicin is the most commonly prescribed in the world. However, its clinical wide application is limited due to harmful side effects like cardiotoxicity. The cardiotoxic mechanism of DOX is not fully clear, however, it is considered as a potential etiological factor to the generation of ROS and Iron complexes, impairment, Ca(2+)homeostasis, mitochondrial dysfunction, and cell membrane damage. Moreover, it is generally believed that mitochondrial dysfunction plays a central role in the cardiotoxic effect of DOX. Additionally, SIRTs are considered to play an important role, which is activated by small energy molecules to generate energy by stimulation of transcription factors and enzymatic regulation of cardiac energy metabolism. In the heart tissue, SIRT1 and SIRT3 are present in large amounts. This review paper focuses on DOX mediated cardiomyopathy & cardiomyocytes death and The modulation of mitochondrial processes by SIRT1, SIRT3, and DOX . This paper expounds from the following aspects, respectively. 1. A target to mitochondria; (1) ROS overproduction under mitochondrial dysfunction; (2) Lipid peroxidation by oxidative stress after ROS over-production; (3) Disturbance of calcium homeostasis and mitochondrial permeability transition; 2. SIRTs participate in the process of cardiotoxicity; (1) SIRT1 and toxic myocardial injury; ?Over-expression of SIRT1 in toxic myocardial injury; ?SIRT1 mediated DOX-induced cardiotoxicity; (2) SIRT3 and mitochondrial damage; ?A central role of SIRT3 in cardiac metabolism; ? Role of SIRT3 in DOX-induced cardiotoxicity; This review is based on SIRTs mediated role in the regulation of mitochondrial function, and evaluates their role on DOX induced cardiotoxicity.

Automated summary

Doxorubicin is a commonly prescribed chemotherapeutic drug worldwide, but its use is limited by harmful side effects like cardiotoxicity. This review paper focuses on the cardiomyopathy and cardiomyocyte death induced by DOX, as well as the roles of SIRT1, SIRT3, and DOX in modulating mitochondrial processes.