title: In vitro evaluation of antifungal and cytotoxic activities as also the therapeutic safety of the oxidized form of amphotericin B.
abstract: The aim of this study was to evaluate the antifungal and cytotoxic activities of the oxidized form of amphotericin B (AmB-Ox) as well as to determine whether oxidation process of AmB is therapeutically beneficial in vitro. The antifungal activity was estimated against Candida albicans ATCC 10231 and Candida parasilosis ATCC 22019 by broth microdilution method according to the NCCLS M27-A2 standards. The in vitro cytotoxicity was evaluated using normal green monkey kidney cells (GMK) by MTT assay. The obtained results demonstrated that AmB-Ox possesses 16-fold decreased antifungal properties against the two Candida strains and 5-fold lower cytotoxic activity towards GMK cells in comparison with AmB. The therapeutic safety in vitro assessed by calculating the ratio between cytotoxicity (CC50 value) to antifungal activity (MIC value) showed that oxidation of AmB is a very unfavourable process in vitro, because leads to formation of derivative (AmB-Ox) that lost antifungal properties much more rapidly than cytotoxic activity. Thus, the process of the oxidation of AmB in vivo (if it occurs) can be also highly harmful for patient.
authors.affiliation: Chair and Department of Biochemistry and Biotechnology, Medical University of Lublin, Chodzki Street 1, 20-093, Lublin, Poland. Electronic address: katarzyna.klimek@umlub.pl.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Klimek
authors.affiliation: Department of Cell Biology, Institute of Biology and Biotechnology, Maria Curie-Skłodowska University, 20-033, Lublin, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Strubińska
authors.affiliation: Department of Biophysics, University of Life Sciences in Lublin, Akademicka 13, 20-950, Lublin, Poland. Electronic address: grzegorz.czernel@up.lublin.pl.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Czernel
authors.affiliation: Chair and Department of Biochemistry and Biotechnology, Medical University of Lublin, Chodzki Street 1, 20-093, Lublin, Poland.
authors.forename: Grazyna
authors.initials: G
authors.lastname: Ginalska
authors.affiliation: Department of Cell Biology, Institute of Biology and Biotechnology, Maria Curie-Skłodowska University, 20-033, Lublin, Poland. Electronic address: mariusz.gagos@poczta.umcs.lublin.pl.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Gagoś
mesh_terms: D000666:Amphotericin B / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002175:Candida / Q000187:drug effects*; D002176:Candida albicans / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D010084:Oxidation-Reduction
chemical_list: D000935:Antifungal Agents; D000666:Amphotericin B
keywords: AmB; AmB-Ox; Antifungal activity; Candida; Cytotoxicity; Therapeutic index