Effect of carnitine and coenzyme Q10 on the calcium uptake in heart sarcoplasmic reticulum of rats treated with anthracyclines.
The effect of the association of carnitine and coenzyme Q10 on doxorubicin cardiotoxicity has been investigated. The two drugs administered to rats for two weeks have lower protective activity when they are administered separately rather than given in association (carnitine 200 mg/kg/day, coenzyme Q10 10 mg/kg/day) for the acute toxic effect of doxorubicin on perfused functioning isolated hearts. The sarcoplasmic reticulum damage measured by calcium-uptake is lower in rat hearts treated with the combined drugs. Deferoxamine and phosphocreatine, two compounds which protect from peroxidative damage due to iron and copper ions, show very strong protection from acute doxorubicin toxicity in isolated perfused hearts. Carnitine and coenzyme Q10 do not protect sarcoplasmic reticulum from iron ions damage, suggesting that their mechanism of protection is not directly related to peroxidation due to metal ion-dependent cardiotoxicity of doxorubicin.
Ronca-Testoni
S
S
Institute of Biological Chemistry, University of Pisa, Italy.
Zucchi
R
R
Ronca
F
F
Bertelli
A
A
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism*; D002331:Carnitine / Q000494:pharmacology*; D003067:Coenzymes; D003326:Coronary Circulation / Q000187:drug effects; D004317:Doxorubicin / Q000633:toxicity; D004338:Drug Combinations; D005296:Ferrous Compounds / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D010070:Oxalates / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D003067:Coenzymes; D004338:Drug Combinations; D005296:Ferrous Compounds; D010070:Oxalates; D014451:Ubiquinone; D004317:Doxorubicin; C024989:coenzyme Q10; D002331:Carnitine; D002118:Calcium