Effect of L-carnitine supplementation on cardiac carnitine palmitoyltransferase activities and plasma carnitine concentrations in adriamycin-treated rats.
Adriamycin (ADR) inhibits the carnitine palmitoyl transferase (CPT) system and consequently the transport of long-chain fatty acids across mitochondrial membranes. l-Carnitine (CARN) plays a major role in fatty acid oxidation by translocating activated long-chain fatty acids into the matrix of mitochondria. CARN has been shown to be of benefit in certain cardiac conditions including cardiomyopathy and myocardial infarction. This study was devised to investigate the effect of CARN on altered CPT I and CPT II activity in the cardiomyopathy associated with ADR therapy. We also assessed the effect of CARN on the plasma free, total, and acylcarnitine concentrations. Four groups, each consisting of four male Sprague-Dawley rats, were studied: group 1(n = 4) was not given either ADR or CARN; group 2 (n = 4) was given ADR (15 and 20 mg/kg, respectively, cumulative dose) by i.p. injections for 1 and 2 wk; group 3 (n = 4) was given the same dose of ADR with CARN (200 mg/kg); and group 4 (n = 4) was given CARN (200 mg/kg). The activities of CPT I and CPT II in heart were significantly decreased in the ADR-treated rats (p < 0.05) in a dose-dependent manner. The reduced activities of CPT I and CPT II, inhibited by ADR, were not normalized by supplementation with CARN (p < 0.05). In rats supplemented with CARN alone, the activities of CPT I and CPT II were elevated approximately 50% above those of the control rats (p < 0.05). ADR treatment resulted in elevation of plasma free and total CARN concentrations (p < 0.05). Supplementation with CARN did not effect the increased plasma CARN concentrations resulting from ADR treatment (p < 0.05). This study supports the concept that ADR toxicity results from the inhibition of both CPT I and CPT II activities and that one of the causes of ADR-induced cardiomyopathy is a result of globally impaired fatty acid oxidation.
Yoon
Hye-Ran
HR
Metabolic Disease Detection Laboratory, Seoul Medical Science Institute, Korea.
Hong
Young Mi
YM
Boriack
Richard L
RL
Bennett
Michael J
MJ
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000378:metabolism; D002331:Carnitine / Q000097:blood / Q000494:pharmacology*; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D002334:Carnitine O-Palmitoyltransferase; D002331:Carnitine