Differences between carnitine derivatives and coenzyme Q10 in preventing in vitro doxorubicin-related cardiac damages.
Anthracycline derivatives are among the most effective and widely used antiblastic drugs. Irreversible and dose-dependent cardiotoxic side effects, however, severely limit their prolonged use. This study sought to establish whether carnitine derivatives or coenzyme Q10 could provide protection against doxorubicin-related cardiac damage. Rat heart slices were incubated for 60 min in a Warburg apparatus at 38 degrees C with 4 mM L-carnitine or 1 mM propionyl carnitine or 15 microM coenzyme Q10 to which 25 microM doxorubicin was added. Cellular oxygen uptake and 14C-leucine incorporation were measured. Carnitine derivatives significantly reduced (p less than 0.001) the metabolic cardiac impairment due to doxorubicin. Incubation for 60 min with a mixture of L-carnitine and doxorubicin improved cellular respiration, oxygen uptake being only 9% less than that of the controls, and an even greater reversal characterized the propionyl carnitine mixture for which the recovery of endogenous cellular respiration was almost complete (93%). Coenzyme Q10 instead provided no significant protection against doxorubicin-induced inhibition. The incorporation of 14C-leucine followed a similar pattern; the addition of carnitine derivatives to doxorubicin served to restore cellular protein synthesis almost totally (from 76 to 97%), whereas coenzyme Q10 produced no significant increment, probably due to the low permeability of the cell membrane to exogenous coenzyme Q10. Thus, levo and propionyl carnitine even more appear to be promising agents in the prevention of doxorubicin-related cardiac toxicity.
Neri
B
B
Istituto di Clinica Medica Generale e Terapia Medica IV, Università degli Studi di Firenze, Italia.
Neri
G C
GC
Bandinelli
M
M
D000818:Animals; D002331:Carnitine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004317:Doxorubicin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis; D009206:Myocardium / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014451:Ubiquinone / Q000494:pharmacology*
D009124:Muscle Proteins; D014451:Ubiquinone; C003223:propionylcarnitine; D004317:Doxorubicin; D002331:Carnitine; D010100:Oxygen