Plandé Joëlle, Platel Denis, Tariosse Liliane, Robert Jacques
Laboratoire de Pharmacologie des Agents Anticancéreux, Institut Bergonié, 229 Cours de l'Argonne, 33076 Bordeaux-cedex, France.
Toxicol Lett. 2006 Feb 8;161(1):37-42. doi: 10.1016/j.toxlet.2005.07.013. Epub 2005 Aug 29.
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.
我们研究了右丙亚胺对目前临床上使用的蒽环类药物（多柔比星、表柔比星、柔红霉素和伊达比星）所致心脏毒性的保护作用，尤其着重于确定右丙亚胺的最佳剂量。这是通过在等心脏毒性剂量使用蒽环类药物，并以蒽环类药物剂量的10倍或20倍使用右丙亚胺进行12天联合治疗后，采用离体灌注大鼠心脏模型来完成的。我们在本研究中表明，右丙亚胺本身无心脏毒性，且能够显著降低蒽环类药物的心脏毒性，同时不会增加这些药物所致的全身毒性。以蒽环类药物剂量的20倍使用右丙亚胺比以蒽环类药物剂量的10倍使用右丙亚胺提供了更好的心脏保护作用；在右丙亚胺剂量较高时，心脏功能参数（舒张末压力、收缩性和舒张性）与对照组动物记录的参数无差异。
