How are anthracyclines cardiotoxic?
Anthracycline-induced cardiotoxicity is due in large part to the generation of free radicals from doxorubicin through mitochondrial redox cycling of doxorubicin in the cardiomyocyte, which ultimately results in left ventricular dysfunction, and in the most severe cases, congestive heart failure.
Why is liposomal doxorubicin less cardiotoxic?
The use of liposomal DOX formulations has reduced cardiotoxicity because of lower myocardial drug concentrations. Liposomes are designed to avoid direct contact of the cytotoxic agent with the vasculature, and influence biodistribution based on leakiness of the endothelium of various organs.
Which patient receiving an anthracycline has the highest risk of cardiotoxicity?
Cumulative doses above 500 mg/m2 in adults and >300 mg/m2 in pediatric patients are associated with a higher risk of therapy-related cardiotoxicity [4, 5].
How does doxorubicin cause cardiomyopathy?
Doxorubicin-induced cardiomyopathy is strongly linked to an increase in cardiac oxidative stress, as evidenced by reactive oxygen species (ROS) induced damage such as lipid peroxidation, along with reduced levels of antioxidants and sulfhydryl groups.
Does anthracycline cause cardiomyopathy?
Anthracycline-induced cardiac dysfunction (ACD) is a notorious side effect of anticancer treatment. It has been described as a phenomenon of a continuous progressive decline of cardiac function, eventually leading to dilated cardiomyopathy (DCM).
What is a risk factor for anthracycline related cardiotoxicity?
Hypertension, diabetes, and obesity were identified as risk factors for anthracycline-induced cardiotoxicity. GLS showed higher detection rate and better early detection ability for cardiotoxicity than LVEF.
Does doxorubicin cause cardiotoxicity?
Doxorubicin is a highly effective anticancer agent but causes cardiotoxicity in many patients. The mechanisms of doxorubicin-induced cardiotoxicity remain incompletely understood.
What is the mechanism of action of doxorubicin?
Doxorubicin has antimitotic and cytotoxic activity through a number of proposed mechanisms of action: Doxorubicin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation- …
What is doxorubicin induced cardiotoxicity?
While an effective anti-tumor agent, doxorubicin causes cumulative and dose-dependent cardiotoxicity, ranging from occult changes in myocardial structure and function to severe cardiomyopathy and congestive heart failure that may result in cardiac transplantation or death1,2,3,4,5,6.
Is anthracycline cardiotoxicity reversible?
Anthracycline induced cardiotoxicity has been categorised into acute, early-onset chronic progressive, and late-onset chronic progressive and is usually not reversible. The risk of clinical cardiotoxicity increases with a number of risk factors including higher total cumulative doses.
What is the mode of action for the anthracycline anticancer agents?
Mechanism of Action The most widely accepted explanation for the action of anthracyclines is their interaction with topoisomerase-II. The ternary complex thus formed prevents the re-ligation of the ds-DNA breaks. Subsequently, it promotes growth arrest and apoptotic cell death.
What type of cardiomyopathy is caused by doxorubicin?
Doxorubicin (Dox) is a highly effective anticancer drug but cause acute ventricular dysfunction, and also induce late-onset cardiomyopathy and heart failure. Despite extensive studies, the pathogenic sequelae leading to the progression of Dox-associated cardiomyopathy remains unknown.