Doxorubicin (DOX) was administered intraperitoneally to rats in six equal,
2.5 mg/kg doses over a 2-week period with or without L-carnitine. Injury wa
s monitored by echocardiography, release of myosin light chain-1 (MLC-1), a
nd by measurement of aldehydic lipid peroxidation products. General observa
tion revealed that DOX alone caused more ascites than DOX plus L-carnitine.
Animals sacrificed 2 h after the sixth dose had significantly higher aldeh
yde concentrations than 2 h after a single dose of DOX. Aldehydes in plasma
and heart remained elevated for 3 weeks after the final dose of DOX, where
as L-carnitine prevented or attenuated the DOX-induced increases in lipid p
eroxidation. The increase in MLC-1 2 h after the sixth dose of DOX was grea
ter than after a single dose, suggesting cumulative damage. Echocardiograph
y did not detect either early injury or the protective effects of L-carniti
ne. These data indicate that lipid peroxidation following DOX occurs early,
and parallels the cumulative characteristics of DOX-induced cardiotoxicity
. The protective effects of L-carnitine may be due to improved cardiac ener
gy metabolism and reduced lipid peroxidation. (C) 1999 Elsevier Science Inc
.