Experimental study of dexrazoxane-anthracycline combinations using the model of isolated perfused rat heart.
We have studied the protective effect of dexrazoxane on the cardiac toxicity induced by the anthracyclines currently used in clinics, doxorubicin, epirubicin, daunorubicin and idarubicin, with special emphasis on determining the optimal dose of dexrazoxane. This was performed using the model of isolated perfused rat heart after 12-day combination treatment of anthracyclines used at equi-cardiotoxic doses, and dexrazoxane used at 10-fold or 20-fold the anthracycline dose. We have shown in this study that dexrazoxane by itself was not cardiotoxic, and was able to significantly reduce anthracycline cardiac toxicity without increasing the general toxicity induced by these drugs. Using dexrazoxane at 20 times the anthracycline dose provided a better cardioprotection than using it at 10 times the anthracycline dose; at the higher dexrazoxane dose, the functional cardiac parameters (developed pressure, contractility and relaxation) were not different from those recorded in control animals.
Plandé
Joëlle
J
Laboratoire de Pharmacologie des Agents Anticancéreux, Institut Bergonié, 229 Cours de l'Argonne, 33076 Bordeaux-cedex, France.
Platel
Denis
D
Tariosse
Liliane
L
Robert
Jacques
J
D000818:Animals; D018943:Anthracyclines / Q000008:administration & dosage / Q000633:toxicity*; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D008297:Male; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D011929:Razoxane / Q000008:administration & dosage / Q000633:toxicity*; D018675:Toxicity Tests; D015430:Weight Gain / Q000187:drug effects; D015431:Weight Loss / Q000187:drug effects
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D011929:Razoxane