Endocannabinoid InhibitionA New Cardioprotective Strategy Against Doxorubicin Cardiotoxicity

摘要

It has been almost 40 years since the quinone-containing anthracycline doxorubicin was first isolated from cultures of Streptomyces peucettus var. caesius (1), and it remains one of the most effective and commonly used drugs for treatment of a variety of solid and hematologic malignancies. There is a strong correlation between total dose and antitumor efficacy; however, soon after its discovery a second effect became evident: patients treated with doxorubicin developed cardiomyopathic changes. This serious side effect has significantly limited its potential clinical utility (2). Initial reports documented the highest risk for doses above 450 mg/m2 (3). However, with improved methods of detecting subtle changes in cardiac function, (e.g., alterations in left ventricular wall stress [4 J), the incidence of doxorubicin cardiotoxicity is now appreciated to be much higher than previously suspected. Alterations in wall stress have been documented in 65% of long-term survivors of childhood cancer, even at doses as low as 228 mg/m (5).