Ascorbic acid decreases the antifungal effect of fluconazole in the treatment of candidiasis
| Autor: | Cao Yingying, Yong-Bing Cao, Wan-Qing Liao, Ming-Bang Li, Ping-Hui Gao, Jian-Hui Jia, Xin-Ming Jia, Yuanying Jiang, Yan Wang |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Antifungal Agents
Physiology Drug Evaluation Preclinical Ascorbic Acid Microbial Sensitivity Tests Pharmacology Antioxidants Acetylcysteine chemistry.chemical_compound Mice Drug Resistance Fungal Physiology (medical) Candida albicans medicine Potency Animals Fluconazole Kidney biology Candidiasis Glutathione biology.organism_classification Ascorbic acid Disease Models Animal medicine.anatomical_structure Mechanism of action chemistry medicine.symptom Drug Antagonism medicine.drug |
| Zdroj: | Clinical and experimental pharmacologyphysiology. 36(10) |
| ISSN: | 1440-1681 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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