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

作者：Daisuke Kobayashi, Kei Kondo, Nobuyuki Uehara, Seiko Otokozawa, Naoki Tsuji, Atsuhito Yagihashi, Naoki Watanabe · 发表于：Antimicrobial Agents and Chemotherapy · 年份：2002 · DOI：10.1128/aac.46.10.3113-3117.2002 · 被引用次数：338 · 研究领域：Antifungal resistance and susceptibility、Fungal Biology and Applications、Fungal Infections and Studies

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 micro g/ml) and was enhanced further in a dose-dependent manner, with a fourfold increase detected when miconazole was used at 12.5 micro g/ml. This increase in the level of ROS production was completely inhibited by pyrrolidinedithiocarbamate (PDTC), an antioxidant, at 10 micro M. 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.