Effects of ascorbic acid and α-tocopherol on the therapeutic index of amphotericin B

Area of Science:

• Mycology
• Pharmacology
• Biochemistry

Background:

• Amphotericin B (AmB) is a crucial antifungal polyene for deep fungal infections.
• AmB's clinical utility is limited by significant toxicity to mammalian cells, primarily via lipid peroxidation.
• Understanding AmB-induced cytotoxicity mechanisms is vital for developing safer antifungal therapies.

Purpose of the Study:

• To evaluate the efficacy of AmB combined with antioxidants (vitamins C and E) against Candida albicans.
• To assess the protective effects of these vitamin-antioxidant formulations on human red blood cells.
• To determine if antioxidant vitamins can mitigate AmB-induced toxicity and improve its therapeutic index.

Main Methods:

• In vitro testing of AmB formulations with vitamin C (ascorbic acid) and vitamin E (α-tocopherol) against Candida albicans ATCC 10231.
• Cytotoxicity assays using human red blood cells to evaluate the safety of AmB-vitamin combinations.
• Comparative analysis of antifungal efficacy and hemotoxicity between AmB alone and AmB-vitamin formulations.

Main Results:

• Formulations containing AmB with vitamins C and E showed a 7-12% improvement in antifungal efficacy compared to AmB alone.
• Vitamins C and E protected human red blood cells from AmB-induced cytotoxicity by 17%.
• Yeast regrowth was observed after 24 hours, irrespective of vitamin C or E complexation, indicating potential limitations in sustained antifungal activity.

Conclusions:

• Incorporating antioxidant vitamins (C and E) into AmB formulations enhances its therapeutic index by improving efficacy and reducing red blood cell toxicity.
• The antioxidant properties of vitamins likely protect against AmB autoxidation and associated cellular damage.
• Further research is needed to address the observed yeast regrowth and optimize sustained antifungal activity.