Efectividad in vitro de tres fármacos aprobados y su interacción sinérgica contra Leishmania infantum

Iman Fathy Abou-El-Naga, Rasha Fadly Mady, Nermine Mogahed Fawzy Hussien Mogahed, .

Palabras clave: Leishmania infantum, sinergismo farmacológico, apoptosis, autofagia

Resumen

Introducción. La leishmaniasis sigue siendo una de las enfermedades tropicales desatendidas. La reutilización de medicamentos existentes ha demostrado ser exitosa para tratar enfermedades tropicales desatendidas y la terapia combinada es una alternativa estratégica para el tratamiento de enfermedades infecciosas.
Auranofin, lopinavir/ritonavir y sorafenib son medicamentos aprobados por la Food and Drug Administration (FDA) de Estados Unidos utilizados en el tratamiento de diversas enfermedades, pues actúan sobre diferentes enzimas biológicas esenciales.
Objetivo. Evaluar los efectos terapéuticos de la monoterapia y de los tres fármacos combinados contra Leishmania infantum.
Materiales y métodos. Los efectos leishmanicidas de los tres fármacos sobre los promastigotes se compararon in vitro en cuanto al recuento de parásitos, la concentración del fármaco que proporcionara una respuesta semimáxima y los cambios ultraestructurales del parásito. Se calculó el índice de concentración inhibitoria de fracciones de fármacos combinados de dos maneras y la actividad de los tres fármacos juntos para determinar el efecto sinérgico.
Resultados. La monoterapia con los tres medicamentos fue efectiva, pero la auranofina tuvo el mejor efecto antileishmanicida con un CE50 de 1,5 μM, en tanto que el sorafinib redujo el crecimiento del parásito con un CE50 de 2,5 μM. La microscopía electrónica de barrido de promastigotes de todos los medios tratados mostró una distorsión en la forma, con pérdida de flagelos y formación de ampollas. La acidocalcinosis fue evidente por microscopía electrónica de transmisión con todos los tratamientos, lo que sugiere apoptosis. El tratamiento con lopinavir/ritonavir mostró signos de autofagia. La combinación de dos medicamentos condujo a interacciones aditivas, mientras que la combinación de las tres drogas produjo una acción sinérgica.
Conclusión. Los tres medicamentos usados como monoterapia contra Leishmania spp. fueron efectivos, pero el tratamiento combinado lo fue en mayor medida debido a los efectos aditivos o sinérgicos.

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  • Iman Fathy Abou-El-Naga Medical Parasitology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt http://orcid.org/0000-0003-1095-7263
  • Rasha Fadly Mady Medical Parasitology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
  • Nermine Mogahed Fawzy Hussien Mogahed Medical Parasitology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt

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Cómo citar
Abou-El-Naga, I. F., Mady, R. F., & Fawzy Hussien Mogahed, N. M. (2020). Efectividad in vitro de tres fármacos aprobados y su interacción sinérgica contra Leishmania infantum. Biomédica, 40(Supl. 1), 89-101. https://doi.org/10.7705/biomedica.4891
Publicado
2020-05-01