Inhibitory effect of terbinafine on reactive oxygen species (ROS) generation by Candida albicans

Abstract

Candida albicans, the most important opportunistic fungal pathogen, is able to generate remarkable amounts of reactive oxygen species (ROS). Since ROS are highly cytotoxic, this mechanism may contribute to the pathogenicity of this yeast, including its invasiveness and the inflammatory response of the host. Terbinafine, a synthetic antifungal agent of the allylamine class, inhibits ergosterol biosynthesis at the level of squalene epoxidase. Furthermore, there is evidence that terbinafine at therapeutic concentrations can be considered a free radical scavenger in vitro and could exert an anti-inflammatory activity in vivo. In this study we investigated whether terbinafine affects the generation of ROS by C. albicans. Blastoconidia of the C. albicans strain 3153A were cultured in YEPG-medium and, subsequently, incubated with different doses of terbinafine (1, 10 and 100 microg ml(-1)) for 10 and 60 min, respectively. ROS generation was measured by lucigenin-enhanced chemiluminescence. Formation of ROS was considerably dependent on cell number. Chemiluminescence signals were measured at a concentration > or = 1 x 10(6) cells ml(-1), with a maximum of 1 x 10(8) cells ml(-)1. Already after 10 min of incubation with terbinafine, a dose-dependent significant inhibition of ROS generation was found (P < 0.05), whereas after 60 min this effect was amplified. In conclusion, terbinafine reduced the ability of C. albicans to generate ROS. Besides the known effect on ergosterol biosynthesis, this mechanism may contribute to its antifungal action.