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Título : Increased calcium permeability is not responsible for the rapid lethal effects of amphotericin B on Leishmania sp.
Autor : Cohen, B. Eleazar
Benaím, Gustavo
Ruiz, Marie-Christine
Michelangeli, Fabi6n
Palabras clave : Amphotericin B
Polyene antibiotic
Calcium
Leishmania
Quin-2
Ethidium bromide
Fecha de publicación : 1990
Editorial : Elsevier Science Publishers B. V. (Biomedical Division)
Citación : Vol. 259;No. 2 pp 286-288
Resumen : The mode of action of the polyene antibiotic amphotericin B (AmB), the drug of choice for the treatment of systemic fungal infections and visceral leishmaniasis, is still unclear. An increase in intracellular Ca2+ concentration ([Ca2+]i), toxic in many cases, has been postulated as a possible lethal mechanism for AmB. Cell permeabilization to ethidium bromide (EB) was used as a criterion of viability. Kinetics of the DNA-EB fluorescent complex formation was studied in ergosterol-containing Leishmania promastigotes. Intracellular Ca2+ concentration was measured using quin-2 fluorescence in parallel aliquots. It is shown in this work that AmB can act as an efficient Ca2+ ionophore. However, the rapid permeabilization effect induced by AmB on these cells was not dependent on an increase in [Ca2+]i. On the contrary, it was found that leishmanicidal effect of AmB was enhanced in the absence of external calcium. Furthermore, A23187 a Ca2+ ionophore did not provoke cell penneabilization to EB.
URI : http://hdl.handle.net/123456789/15647
ISSN : https://doi.org/10.1016/0014-5793(90)80028-H
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