Molecular mechanisms of cardiotoxicity: A review on the major side-effects of doxorubicin

Abstract

Doxorubicin is among the most widely used drugs for the treatment of both adult and child cancers. Doxorubicin is the major cause of chemotherapy-induced cardiotoxicity that is dose limiting for the treatment of cancer. Many studies have explored pathophysiology and mechanisms of doxorubicin-induced cardiotoxicity. Cellular and animal experiments proposed that doxorubicin-induced cardiotoxicity mechanism is multifactorial. Oxidative stress has been considered as the primary cause of cardiotoxicity. Although there is no effective treatment for doxorubicin-induced cardiotoxicity currently but many investigations are underway to discover preventive treatments whereas no specific treatment has been approved. Studies have shown that reactive oxygen species and topoisomerase 2b are molecular targets for cardioprotection. Therapeutic imaging methods and cardio-biomarkers may be helpful in the improvement of rapid detection of cardiac damage. In this review, effects of doxorubicin on DNA damage, free radical generation, mitochondrial damage, cell death and other parameters have been studied.