Anthracycline-Induced Cardiotoxicity

Abstract

The anthracyclines constitute a group of drugs widely used for the treatment of a variety of human tumors. However, the development of irreversible cardiotoxicity has limited their use. Anthracycline-induced cardiotoxicity can persist for years with no clinical symptoms. However, its prognosis becomes poor after the development of overt heart failure, possibly even worse than ischemic or idiopathic dilated cardiomyopathies. Due to the successful action of anthracyclines as chemotherapic agents, several strategies have been tried to prevent/attenuate their side effects. Although anthracycline-induced injury appears to be multifactorial, a common denominator among most of the proposed mechanisms is cellular damage mediated by reactive oxygen species. However, it remains controversial as to whether antioxidants can prevent such side effects given that different mechanisms may be involved in acute versus chronic toxicity. The present review applies a multisided approach to the critical evaluation of various hypotheses proposed over the last decade on the role of oxidative stress in cardiotoxicity induced by doxorubicin, the most used anthracycline agent. The clinical diagnosis and treatment is also discussed.

A supplementary report on the toxic manifestations of CHOP regimen in subjects with intermediate grade NHL

“…Also it was observed that the serum levels of transaminases, phosphatase and bilirubin went upto the levels grade 3 & 4 toxicities whereas the hepatomegaly did not progress beyond grade 2 in any of the patient till 6 th cycle. The increase in liver damage and subsequent release & increase of serum hepatic biomarkers may be due to the free radical generation by the chempotherapeutics during their metabolism in the liver (Ferreira et al, 2008).…”

Protective Effects of Salidroside on Epirubicin-Induced Early Left Ventricular Regional Systolic Dysfunction in Patients with Breast Cancer

“…Although the pathogenesis of epirubicin-induced cardiotoxicity remains controversial, the oxidative stress-based hypothesis has gained the widest acceptance. [10] Robust generation of ROS is defined as oxidative stress, and significant increases in generation of ROS (a collective name for hydrogen peroxide, superoxide, and hydroxyl radicals) in cardiomyocytes, as well as serum concentrations, have been reported in epirubicin-induced cardiotoxicity. [10,11] ROS are excessively generated from a likely mitochondrial source, then hasten lipid peroxidation and DNA damage, and consequently initiate cell apoptosis or necrosis.…”

“…[10] Robust generation of ROS is defined as oxidative stress, and significant increases in generation of ROS (a collective name for hydrogen peroxide, superoxide, and hydroxyl radicals) in cardiomyocytes, as well as serum concentrations, have been reported in epirubicin-induced cardiotoxicity. [10,11] ROS are excessively generated from a likely mitochondrial source, then hasten lipid peroxidation and DNA damage, and consequently initiate cell apoptosis or necrosis. [12,13] Accordingly, successful antioxidant interventions targeted to reduce ROS offer insights into preventing epirubicin-induced cardiotoxicity.…”

Improving the Tumor-Specific Delivery of Doxorubicin in Primary Liver Cancer

“…Cardiotoxicity is the main drawback of anthracycline, which restraints more effective application of this drug to liver cancer patients (Ferreira et al, 2008). Myocardial degeneration is the most commonly encountered side-effects of anthracycline (Combs & Acosta, 1990).…”