A REVIEW ON DOXORUBICIN INDUCED CARDIOTOXICITY AND ITS MOLECULAR MECHANISM

Doxorubicin (DOX), an anthracycline antibiotic that is highly used for cancer treatment (chemotherapy), but its chemotherapeutic application is limited due to its cardiotoxicity. The major mechanism of doxorubicin action as the free radical formation and as an inhibiter of topoisomerase II and other signaling pathways is also invoked significant consequence for the cardiomyocyte. But the years of clinical use of doxorubicin generates a need for monitoring the procedure of cardiotoxicity as well as understanding its potential. Peak plasma concentration plays a key role in causing cardiotoxicity and antineoplastic activity. There are two mechanisms, the first one is anti-tumor action, and second one is cardiotoxicity. Cardiotoxicity mechanism has several pathways 1) formation of reactive oxygen and nitrogen species 2) interaction of calcium overload 3) disturb the serum biomarker levels 4) DNA damage. These are the main pathways to cause cardiotoxicity. Some signs and symptoms are given to identify doxorubicin cardiotoxicity like echocardiographical changes, angiographic changes, and disturbance in the serum biomarkers level like GSH, LDH and CK-MB. Some drugs are used to minimize the cardiac side effects like dexrazoxane and rimonabant like drugs administered before the doxorubicin administration but there are some limitations due to its serious side effects. Antioxidant therapy may be the right option for the prevention of doxorubicin cardiotoxicity because the main cause of cardiotoxicity is oxidative stress. So, this review suggested that during the treatment of cancer patients with doxorubicin, cardiovascular monitoring is necessary for patient safety, and further studies are required to add some antioxidant therapy with doxorubicin to prevent patients from the cardiac toxicity.