Mechanism of the Cardioprotective Effects of Docetaxel Pre-administration Against Adriamycin-Induced Cardiotoxicity

作者：Tomonari Mari; To Hideto^*; Nishida Motohiro; Mishima Takashi; Sasaki Hitoshi; Kurose Hitoshi

来源：Journal of Pharmacological Sciences, 2011, 115(3): 336-345.

DOI：10.1254/jphs.10279FP

• docetaxel
• adriamycin
• cardiotoxicity
• free radical
• pre-administration

We revealed that pre-treatment with docetaxel (DOC) 12 h before adriamycin (ADR) administration significantly reduced ADR-induced toxic death compared with the simultaneous dosing schedule that was commonly used in previous studies. We considered that pre-treatment with DOG relieves ADR-induced cardiotoxicity. In this study, we investigated the influence of DOG on the pharmacokinetics and pharmacodyamics of ADR in order to clarify the mechanism by which DOG pre-treatment relieves ADR-induced cardiotoxicity. When ADR and/or DOG was intravenously administered, the DOG pre-treatment (DOG-ADR) group showed significantly less toxic death than the ADR-alone group. We examined hepatopathy, nephropathy, leukopenia, and cardiotoxicity, all of which can cause toxic death. Of these toxicities, ADR-induced cardiotoxicity was significantly relieved in the DOG-ADR group. To elucidate the mechanism by which DOG pre-treatment relieved ADR-induced cardiotoxicity, lipid peroxidation as a proxy for the free radical level and the pharmacokinetics of ADR were measured. There was no difference in the pharmacokinetics of ADR between the ADR and DOG-ADR groups. On the other hand, the DOG-ADR group showed significantly inhibited lipid peroxidation in the heart compared with the ADR group. It was considered that DOG pre-administration inhibited ADR-induced free radicals and decreased cardiotoxicity.

• 出版日期2011-3