A. Mijares et Jr. Lopez, L-carnitine prevents increase in diastolic [Ca2+] induced by doxorubicin in cardiac cells, EUR J PHARM, 425(2), 2001, pp. 117-120
Doxorubicin is a highly effective anticancer chemotherapeutic agent that pr
oduces a dose-dependent cardiomyopathy that limits its clinical usefulness.
We investigated the acute effects of doxorubicin on diastolic free Ca2+. c
oncentrations ([Ca2+]) and the cardioprotective action Of L-carnitine in is
olated cardiomyocytes loaded with fura-2/AM (acetoxymethyl ester). Exposure
to 10(-6)-10(-4) M doxorubicin induced an elevation of diastolic calcium c
oncentration ([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 cardi
omyocytes 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 increas
e in [Ca2+] induced by this anthracycline derivative. These results indicat
e that acute exposure to doxorubicin impairs intracellular Ca2+ handling an
d that L-carnitine exerts a cardioprotective effect, in part by preventing
the doxorubicin-induced increase in diastolic Ca2+ concentration. (C) 2001
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