No evidence of oxidant events in amphotericin B cytotoxicity versusL. infantumpromastigotes

N. Azas, C. Di Giorgio, F. Delmas, M. Gasquet, P. Timon-David
2001 Parasite  
Amphotericin B is used for the treatment of systemic mycoses and visceral leishmaniasis. The objective of our study was to evaluate the impact of catalase, ascorbic acid and ketoconazole on the amphotericin B toxicity towards Leishmania promastigotes membrane by two flow cytometric tests, the membrane potential assay using a cationic dye, [DiOC 5 (3), and the membrane permeability test using propidium iodide. The collapse of membrane potential appeared at amphotericin B concentrations weaker
more » ... n those assessed by the membrane permeability test. The binding of amphotericin B to membrane sterol was not modified by catalase or ascorbic acid whereas amphotericin Binduced growth inhibition could be modulated by these products. The permeabilizing effect of amphotericin B on parasite membrane was strongly reduced in the presence of ketoconazole. These results confirmed the pore hypothesis of amphotericin B action and suggested that flow cytometric methods constituted a valuable alternative to conventional methods for assessing the effect of drugs on cellular membrane and evaluating parasite susceptibility to polyene antibiotics. KEY WORDS : Leishmania infantum, membrane potential, antibiotic susceptibility, membrane permeability, amphoteri ci n B, ketoconazol e, ascorbi c acid, catal ase.
doi:10.1051/parasite/2001084335 pmid:11802270 fatcat:2rehko2z2rhbnn3p4bzjqlos7i