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Ascorbic acid decreases the antifungal effect of fluconazole in the treatment of candidiasis
Author(s) -
Wang Yan,
Jia XinMing,
Jia JianHui,
Li MingBang,
Cao YingYing,
Gao PingHui,
Liao WanQing,
Cao YongBing,
Jiang YuanYing
Publication year - 2009
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2009.05187.x
Subject(s) - ascorbic acid , fluconazole , in vitro , candida albicans , pharmacology , systemic candidiasis , glutathione , kidney , cimetidine , chemistry , in vivo , corpus albicans , toxicity , medicine , biology , antifungal , biochemistry , microbiology and biotechnology , enzyme , food science
Summary1 The aim of the present study was to investigate the effects of ascorbic acid (AA) on the antifungal activity of fluconazole (FCZ) in a systemic murine candidiasis model as well as in vitro . 2 The murine model was established by infusion of Candida albicans via the tail vein. Control mice received no further treatment. Other groups of mice were injected with FCZ (0.5 mg/kg, i.p.) and then treated or not with 50 or 500 mg/kg AA intragastrically (i.g.) or i.p. In all groups, FCZ was administered i.p. 2 h after fungal inoculation, whereas AA was administered 6 h after fungal inoculation. Survival rate, kidney fungal burden and renal pathological changes were evaluated. 3 The in vitro effects of AA (5, 1 and 0.2 mmol/L) on the growth of various Candida strains in the presence of FCZ (0.125–64 µg/mL) were also investigated. The in vitro effects of two anti‐oxidants, namely N ‐acetylcysteine (NAC; 5, 1 and 0.2 mmol/L) and reduced glutathione (GSH; 5, 1 and 0.2 mmol/L), on FCZ activity were evaluated to determine the mechanism of action of AA. 4 Intragastric administration of AA (50 or 500 mg/kg) significantly decreased the antifungal effect of 0.5 mg/kg FCZ. Although i.p. administration of AA (50 or 500 mg/kg) had no significant effect on the survival of mice, it dose‐dependently inhibited the activity of FCZ, with significant inhibition observed with 500 mg/kg AA. 5 In vitro , AA decreased the activity of FCZ against various Candida strains. Both NAC and GSH dose‐dependently decreased the activity of FCZ. 6 The results of the present study indicate that AA inhibits the antifungal activity of FCZ, suggesting that the two should not be used together clinically for the treatment of candidiasis.