Cardiac Toxicity of Anthracyclines

Abstract

Cardiotoxicity of anthracyclines limits their therapeutic potential. In the in vitro acute model, anthracyclines produce cardiotoxicity in minutes or hours at concentrations near 100 μM, through a mechanism involving impairment of sarcoplasmic reticulum (SR) function and requiring the quinone moiety, most likely through a non-free-radical process. The chronic cardiotoxicity is more complex, but may also involve SR. Additional mechanisms in the chronic model of anthracycline cardiotoxicity may include impairment of triiodothyronine function, cardiac protein degradation, free-radical generation, apoptosis, cardiac metabolite formation, impairment of iron metabolism and oestrogen-dependent up-regulation of nitric oxide synthase (NOS). Thus, prevention or attenuation of anthracycline cardiotoxicity may be achieved by favourably manipulating these mechanisms. Keywords: anthracyclines; cardiotoxicity; heart failure; calcium; free radicals; ageing