Oxidative effects of the human antifungal drug clotrimazole on the eucaryotic model organism Saccharomyces cerevisiae

Abstract

Clotrimazole is a type of antifungal medication developed from azole compounds. It exhibits several biological actions linked to oxidative stress. This study focuses on the oxidative effects of clotrimazole on the eukaryotic model yeast, Saccharomyces cerevisiae. Our results showed that although initial nitric oxide levels were above control in clotrimazole exposed cells, they showed decreasing tendencies from the beginning of incubation and dropped below control at 125 mu M from the 60th min. The highest superoxide anion and hydrogen peroxide levels were 1.95- and 2.85-folds of controls at 125 mu M after 15 and 60 min, respectively. Hydroxyl radical levels slightly increased throughout the incubation period in all concentrations and reached 1.3-fold of control, similarly at 110 and 125 mu M in the 90th min. The highest level of reactive oxygen species was observed at 110 mu M, 2.31-fold of control. Although NADH/NADPH oxidase activities showed similar tendencies for all conditions, the highest activities were found as 3.07- and 2.27-folds of control at 125 and 110 mu M in the 15th and 30th min, respectively. The highest superoxide dismutase and catalase activities were 1.59- and 1.21-folds of controls at 110 mu M clotrimazole in 30 and 90 min, respectively. While the drug generally induced glutathione-related enzyme activities, the ratios of glutathione to oxidized glutathione were above the control only at low concentrations of the drug. The levels of lipid peroxidation in all treated cells were significantly higher than the controls. The findings crucially demonstrate that this medicine can generate serious oxidative stress in organisms.