Mechanism of the cardioprotective effects of docetaxel pre-administration against adriamycin-induced cardiotoxicity

Mari Tomonari, Hideto To, Motohiro Nishida, Takashi Mishima, Hitoshi Sasaki, Hitoshi Kurose

研究成果: Contribution to journalArticle査読

9 被引用数 (Scopus)

抄録

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 DOC relieves ADR-induced cardiotoxicity. In this study, we investigated the influence of DOC on the pharmacokinetics and pharmacodynamics of ADR in order to clarify the mechanism by which DOC pre-treatment relieves ADR-induced cardiotoxicity. When ADR and/or DOC was intravenously administered, the DOC pre-treatment (DOC-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 DOC-ADR group. To elucidate the mechanism by which DOC 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 DOC-ADR groups. On the other hand, the DOC-ADR group showed significantly inhibited lipid peroxidation in the heart compared with the ADR group. It was considered that DOC pre-administration inhibited ADR-induced free radicals and decreased cardiotoxicity.

本文言語英語
ページ(範囲)336-345
ページ数10
ジャーナルJournal of Pharmacological Sciences
115
3
DOI
出版ステータス出版済み - 2011

All Science Journal Classification (ASJC) codes

  • 分子医療
  • 薬理学

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