L-carnitine attenuates doxorubicin-induced lipid peroxidation in rats.
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 was monitored by echocardiography, release of myosin light chain-1 (MLC-1), and by measurement of aldehydic lipid peroxidation products. General observation revealed that DOX alone caused more ascites than DOX plus L-carnitine. Animals sacrificed 2 h after the sixth dose had significantly higher aldehyde 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, whereas L-carnitine prevented or attenuated the DOX-induced increases in lipid peroxidation. The increase in MLC-1 2 h after the sixth dose of DOX was greater than after a single dose, suggesting cumulative damage. Echocardiography did not detect either early injury or the protective effects of L-carnitine. 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 energy metabolism and reduced lipid peroxidation.
Luo
X
X
Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada.
Reichetzer
B
B
Trines
J
J
Benson
L N
LN
Lehotay
D C
DC
D000447:Aldehydes / Q000097:blood / Q000378:metabolism; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D002331:Carnitine / Q000008:administration & dosage / Q000494:pharmacology*; D004317:Doxorubicin / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D004452:Echocardiography; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D018994:Myosin Light Chains / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000447:Aldehydes; D000903:Antibiotics, Antineoplastic; D018994:Myosin Light Chains; D004317:Doxorubicin; D002331:Carnitine