title: Effects of ascorbic acid and α-tocopherol on the therapeutic index of amphotericin B.
abstract: Amphotericin B (AmB) remains the antifungal polyene of choice in deep fungal infections, but its high toxicity to mammalian cells limits its use. This toxicity is partly due to lipid peroxidation exerted by amphotericin B in cell membranes. The work we have undertaken focused on the one part the evaluation of the efficacy of amphotericin B in the presence of some antioxidants vitamins (vitamin C "ascorbic acid" and vitamin E "α-tocopherol") against the yeast Candida albicans ATCC 10231. Secondly, we have tested the cytotoxicity of these formulations on human red blood cells. The results showed a significant improvement in the efficiency of our formulations tested from 7% to 12% compared with amphotericin B alone at therapeutic concentrations. Furthermore, the addition of vitamin C and vitamin E protects human red blood cells against the cytotoxicity induced by amphotericin B with 17%. This is due may be to the antioxidant power of vitamins which confer protection against the autoxidation of the molecule of amphotericin B. On the other hand, it is noticed that the yeast regrows after 24h whatever in complex with vitamin C or vitamin E of the stock solution. On completion of this study, the incorporation of antioxidant vitamins that we propose to the reaction medium of antifungal improved the therapeutic index of amphotericin B.
authors.affiliation: Laboratoire antibiotiques antifongiques : physico-chimie, synthèse et activité biologique, département de biologie, faculté des Sciences de la Nature et de la Vie, des Sciences de la Terre et de l'Univers, université de Tlemcen, Tlemcen, Algeria. Electronic address: asouatou@yahoo.fr.
authors.forename: M H
authors.initials: MH
authors.lastname: Belhachemi
authors.affiliation: Laboratoire antibiotiques antifongiques : physico-chimie, synthèse et activité biologique, département de biologie, faculté des Sciences de la Nature et de la Vie, des Sciences de la Terre et de l'Univers, université de Tlemcen, Tlemcen, Algeria.
authors.forename: K
authors.initials: K
authors.lastname: Boucherit
authors.affiliation: Laboratoire antibiotiques antifongiques : physico-chimie, synthèse et activité biologique, département de biologie, faculté des Sciences de la Nature et de la Vie, des Sciences de la Terre et de l'Univers, université de Tlemcen, Tlemcen, Algeria.
authors.forename: Z
authors.initials: Z
authors.lastname: Boucherit-Otmani
authors.affiliation: Laboratoire antibiotiques antifongiques : physico-chimie, synthèse et activité biologique, département de biologie, faculté des Sciences de la Nature et de la Vie, des Sciences de la Terre et de l'Univers, université de Tlemcen, Tlemcen, Algeria.
authors.forename: S
authors.initials: S
authors.lastname: Belmir
authors.affiliation: Laboratoire antibiotiques antifongiques : physico-chimie, synthèse et activité biologique, département de biologie, faculté des Sciences de la Nature et de la Vie, des Sciences de la Terre et de l'Univers, université de Tlemcen, Tlemcen, Algeria.
authors.forename: Z
authors.initials: Z
authors.lastname: Benbekhti
mesh_terms: D000666:Amphotericin B / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000009:adverse effects / Q000494:pharmacology*; D002176:Candida albicans; D004347:Drug Interactions; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D010084:Oxidation-Reduction / Q000187:drug effects; D018675:Toxicity Tests; D024502:alpha-Tocopherol / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D000666:Amphotericin B; D024502:alpha-Tocopherol; D001205:Ascorbic Acid
keywords: Acide ascorbique (vitamine C); Activité antifongique; Amphotericin B; Amphotéricine B; Antifungal activity; Ascorbic acid (vitamin C); Candida albicans; Dormance; Dormancy; Selective toxicity; Toxicité sélective; α-Tocopherol (vitamin E); α-Tocophérol (vitamine E)