Della Torre P, Podesta A, Pinciroli G, Iatropoulos M J, Mazué G
Toxicology and Safety Assessment, Pharmacia, Milan, Italy.
Toxicol Pathol. 1996 Jul-Aug;24(4):398-402. doi: 10.1177/019262339602400402.
The long-lasting protective effect of dexrazoxane (ADR-529) against doxorubicin- and epirubicin-induced cardiotoxicity was evaluated in the multiple-dose 35-wk rat model. Groups of 36 male Sprague-Dawley rats were given ADR-529 30 min before administration of cardiotoxic doses of doxorubicin (1 mg/kg/wk) or epirubicin (1.13 mg/kg/wk). The compounds were intravenously injected once weekly for 7 consecutive wk at ADR-529; anthracycline ratios ranging from 5:1 to 20:1. These ratios covered the entire chemotherapeutic range in humans and allowed studying the chronic progressive cardiomyopathy in our rat model. Animals were observed for up to 35 wk to follow the time course of the well-characterized cardiomyopathy, which was evaluated through the well-established qualitative/quantitative morphological grading. It was clearly demonstrated in this rat model that ADR-529, at the ratios administered, provided ample cardioprotection for a duration of 35 wk, which corresponds to 25 yr of equivalent human time.
在多剂量35周龄大鼠模型中评估了右丙亚胺（ADR-529）对阿霉素和表柔比星诱导的心脏毒性的长期保护作用。将36只雄性Sprague-Dawley大鼠分为几组，在给予心脏毒性剂量的阿霉素（1mg/kg/周）或表柔比星（1.13mg/kg/周）前30分钟给予ADR-529。以ADR-529与蒽环类药物5:1至20:1的比例，每周静脉注射一次，连续7周。这些比例涵盖了人类的整个化疗范围，并有助于在我们的大鼠模型中研究慢性进行性心肌病。观察动物长达35周，以跟踪特征明确的心衰病程，通过成熟的定性/定量形态学分级进行评估。在该大鼠模型中清楚地表明，以所给予的比例使用ADR-529，可提供长达35周的充分心脏保护，这相当于人类25年的时间。
