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

• Main Authors: Mari Tomonari (Author), Hideto To (Author), Motohiro Nishida (Author), Takashi Mishima (Author), Hitoshi Sasaki (Author), Hitoshi Kurose (Author)
• Format: Book
• Published: Elsevier, 2011-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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. Keywords:: docetaxel, adriamycin, cardiotoxicity, free radical, pre-administration

Item Description

1347-8613
10.1254/jphs.10279FP