Clin Exp Pharmacol Physiol. 2009 Apr 27. [Epub ahead of print]
Ascorbic acid decreases the antifungal effect of fluconazole in the treatment of candidiasis.
Wang Y, Jia XM, Jia JH, Li MB, Cao YY, Gao PH, Liao WQ, Cao YB, Jiang YY. School of Pharmacy, Second Military Medical University, Shanghai 200433, PR China.
1. 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 and in vitro.
2. Murine model was established by infusion of Candida albicans via the tail vein. FCZ (0.5 mg/kg) was given to animals in the corresponding groups intraperitoneally; AA was given to animals intragastrically or intraperitoneally at 50 mg/kg or 500 mg/kg. The survival rate, kidney fungal burden and renal pathological changes were evaluated. The in vitro effects of AA (5, 1, and 0.2 mM) on growth of various Candida strains in the presence of FCZ were investigated. The in vitro effects of two anti-oxidants, N-acetylcysteine (5, 1 and 0.2 mM) and reduced glutathione (5, 1 and 0.2 mM), on FCZ activity were determined to investigate the mechanism of AA's action.
3. We found that intragastric administration of AA (50 or 500 mg/kg) significantly decreased the antifungal effect of 0.5 mg/kg FCZ. Although intraperitoneal administration of AA (50 or 500 mg/kg) had no significant effect on the survival of mice, it inhibited the activity of FCZ dose-dependently; the inhibition was significant when AA was at 500mg/kg. In vitro, AA decreased the activity of FCZ against various Candida strains, and N-acetylcysteine and reduced glutathione decreased the activity of FCZ dose-dependently.
4. Our results demonstrate that AA can inhibit the antifungal activity of FCZ, suggesting that the two should not be used together clinically for treatment of candidiasis.
PMID: 19413603 [PubMed - as supplied by publisher]