Endogenous Reactive Oxygen Species Is an Important Mediator of Miconazole Antifungal Effect

Author:

Kobayashi Daisuke12,Kondo Kei2,Uehara Nobuyuki2,Otokozawa Seiko2,Tsuji Naoki12,Yagihashi Atsuhito12,Watanabe Naoki12

Affiliation:

1. Department of Clinical Laboratory Medicine

2. Division of Laboratory Diagnosis, Sapporo Medical University School of Medicine, Sapporo, Japan

Abstract

ABSTRACT We investigated the significance of endogenous reactive oxygen species (ROS) produced by fungi treated with miconazole. ROS production in Candida albicans was measured by a real-time fluorogenic assay. The level of ROS production was increased by miconazole at the MIC (0.125 μg/ml) and was enhanced further in a dose-dependent manner, with a fourfold increase detected when miconazole was used at 12.5 μg/ml. This increase in the level of ROS production was completely inhibited by pyrrolidinedithiocarbamate (PDTC), an antioxidant, at 10 μM. In a colony formation assay, the decrease in cell viability associated with miconazole treatment was significantly prevented by addition of PDTC. Moreover, the level of ROS production by 10 clinical isolates of Candida species was inversely correlated with the miconazole MIC ( r = −0.8818; P < 0.01). These results indicate that ROS production is important to the antifungal activity of miconazole.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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