Preadministration of Docetaxel Increases Antioxidant Activity in Myocardial Tissue

Abstract

Adriamycin (ADR)-induced cardiotoxicity was previously shown to be attenuated by the preadministration of docetaxel (DOC-ADR), with DOC given 12 h before ADR, and may involve the inhibition of ADR-induced increases in free radical production in myocardial tissue. However, the mechanisms by which DOC suppresses the production of free radicals remain unclear. Therefore, we herein investigated the mechanisms responsible in more detail. The direct effects of DOC on free radical scavenging were examined using a primary cardiomyocyte culture system and the organic radical 2,2-diphenyl-1-picrylhydrazyl (DPPH). To assess the indirect effects of DOC, in vivo components with radical-scavenging activities were measured after the administration of DOC. Cell viability did not improve in the DOC-ADR group, and was lower than that in the ADR group. Furthermore, DOC did not scavenge DPPH. The radical-scavenging activities of antioxidant enzymes did not significantly differ between the DOC-ADR and ADR groups. On the other hand, ceruloplasmin (CP) oxidase activity, which acts on iron ions and suppresses reactive oxygen species (ROS) production, showed a marked transient change that peaked at 12 h after DOC was given (just before the administration of ADR). Therefore, ADR-induced ROS production may have been suppressed by CP activity, which was increased by the preadministration of DOC.

Keywords: adriamycin; cardiotoxicity; ceruloplasmin; docetaxel; free radical.