Ascorbic acid decreases the antifungal effect of fluconazole in the treatment of candidiasis.
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 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 microg/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.
School of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China.
Yan
Y
Wang
Xin-Ming
XM
Jia
Jian-Hui
JH
Jia
Ming-Bang
MB
Li
Ying-Ying
YY
Cao
Ping-Hui
PH
Gao
Wan-Qing
WQ
Liao
Yong-Bing
YB
Cao
Yuan-Ying
YY
Jiang
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy* / Q000401:mortality; D004195:Disease Models, Animal; D004336:Drug Antagonism; D004353:Drug Evaluation, Preclinical; D025141:Drug Resistance, Fungal / Q000187:drug effects; D015725:Fluconazole / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008826:Microbial Sensitivity Tests
D000935:Antifungal Agents; D000975:Antioxidants; D015725:Fluconazole; D001205:Ascorbic Acid