aim: Ascorbate can inhibit growth and even decrease viability of various microbial species including Candida albicans. However the optimum conditions and the mechanism of action are unclear. Materials/methodology: Candida albicans shaken for 90 min in a buffered solution of ascorbate (90 mM) gave a 5-log reduction of cell viability, while there was no killing without shaking, in growth media with different carbon sources or at 4°C. Killing was inhibited by the iron chelator 2,2′-bipyridyl. Hydroxyphenyl fluorescein probe showed the intracellular generation of hydroxyl radicals. Results/conclusion: Ascorbate-mediated killing of C. albicans depends on oxygenation and metabolism, involves iron-catalyzed generation of hydroxyl radicals via Fenton reaction and depletion of intracellular NADH. Ascorbate could serve as a component of a topical antifungal therapy.
Keywords• ascorbate • Candida albicans • hydroxyl radicals • oxidative stress • vitamin C Candida albicans is a major opportunistic fungal pathogen that is associated with a range of clinical conditions. The organism can lead to superficial infections of genital, oral and cutaneous sites as well as systemic infections, especially in hospitalized and/or immunocompromised patients, such as those suffering from AIDS or undergoing chemotherapy [1][2][3][4]. Although most superficial infections caused by C. albicans are not life threatening, these infections can have debilitating effects on the patient's quality of life. Several classes of antifungal agents (e.g., azoles, echinocandins) have been developed which are active against Candida infections; however, possible drug interactions and adverse side-effects, emergence of drug-resistant isolates, as well as the high costs of some of these agents underscore the necessity for development of additional treatment alternatives [3,5].Ascorbate (vitamin C, ascorbic acid) is an essential vitamin and is considered to be a potent antioxidant owing to its ability to act as an electron-donating reducing agent, and a quencher of reactive oxygen species (ROS) [6]. However, there is also increasing evidence that at pharmacologic concentrations, ascorbate can exert pro-oxidant effects via the reduction of transition metal ions, such as iron and copper [7]. Previous studies have shown that high-dose ascorbate exerts selective cytotoxic effects on cancer cells both in vitro and in vivo [6,8]. There have also been several clinical trials in cancer patients, testing the effects of high-dose ascorbate either alone or in For reprint orders, please contact: reprints@futuremedicine.com