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Sodium ascorbate kills Candida albicans in vitro via iron-catalyzed Fenton reaction: importance of oxygenation and metabolism

    Pinar Avci

    Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA

    Department of Dermatology, Harvard Medical School, Boston, MA 02115, USA

    Department of Dermatology, Venerology & Dermato-Oncology, Semmelweis University, Budapest 1085, Hungary

    ,
    Fernanda Freire

    Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA

    Department of Biosciences & Oral Diagnosis, Institute of Science & Technology, Universidade Estadual Paulista (UNESP), São José dos Campos, São Paulo 12245-000, Brazil

    ,
    Andras Banvolgyi

    Department of Dermatology, Venerology & Dermato-Oncology, Semmelweis University, Budapest 1085, Hungary

    ,
    Eleftherios Mylonakis

    Infectious Diseases Division, Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI 02912, USA

    ,
    Norbert M Wikonkal

    *Author for correspondence:

    E-mail Address: wikonkal@gmail.com

    Department of Dermatology, Venerology & Dermato-Oncology, Semmelweis University, Budapest 1085, Hungary

    &
    Michael R Hamblin

    **Author for correspondence:

    E-mail Address: hamblin@helix.mgh.harvard.edu

    Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA

    Department of Dermatology, Harvard Medical School, Boston, MA 02115, USA

    Harvard-MIT Division of Health Sciences & Technology, Cambridge, MA 02139, USA

    Published Online:https://doi.org/10.2217/fmb-2016-0063

    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.

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