L-carnitine prevents increase in diastolic [CA2+] induced by doxorubicin in cardiac cells

Doxorubicin is a highly effective anticancer chemotherapeutic agent that produces a dose-dependent cardiomyopathy that limits its clinical usefulness. We investigated the acute effects of doxorubicin on diastolic free Ca2+ concentrations ([Ca2+]) and the cardioprotective action of L-carnitine in isolated cardiomyocytes loaded with fura-2/AM (acetoxymethyl ester). Exposure to 10(-6)-10(-4) M doxorubicin induced an elevation of diastolic calcium concentration ([Ca2+]) that was concentration dependent. Nitrendipine failed to prevent the doxorubicin-induced elevation of [Ca2+]. Incubation with L-carnitine (10(-8) to 10(-6) M) did not modify [Ca2+]. Pretreatment of cardiomyocytes with L-carnitine 10(-8)-10(-7) M did not prevent the doxorubicin effect on [Ca2+]. However, L-carnitine 10(-6) M fully inhibited the increase in [Ca2+] induced by this anthracycline derivative. These results indicate that acute exposure to doxorubicin impairs intracellular Ca2+ handling and that L-carnitine exerts a cardioprotective effect, in part by preventing the doxorubicin-induced increase in diastolic Ca2+ concentration.