Annona muricata fruit extract protects against diethylnitrosamineinduced hepatocellular cancer in rats
Objective: To evaluate the combination of several statins (atorvastatin, fluvastatin and simvastatin) and azoles (voriconazole, posaconazole and itraconazole) against Acanthamoeba spp. Methods: The efficiency of the different drug combinations against the trophozoite stage of different Acanthamoeba strains were evaluated by Alamar Blue assay. Effect on the cyst stage was observed by inverted microscope. Cytotoxicity of combinations of azoles and statins was evaluated by measuring the release of lactate dehydrogenase from a murine macrophage cell line. Results: Combinations of any of the tested statins and voriconazole or posaconazole were more efficient in inhibiting Acanthamoeba compared to statins or azoles individually. The drug combinations at the combined inhibitory concentrations 50% showed lower toxicity compared to that of the compounds alone. Conclusions: The combinations of statins together with voriconazole and posaconazole are more efficient than these drugs alone, and these combinations have lower cytotoxicity in mammalian cell lines.
This work was supported by the grants Red de Investigation Colaborativa en Enfermedades Tropicales RICET (project no. RD16/0027/0001 of the programme of Redes Temáticas de Investigación Cooperativa, FIS), Spanish Ministry of Health, Madrid, Spain and PI13/00490 “Protozoosis Emergentes por Amebas de Vida Libre: Aislamiento, Caracterización, Nuevas Aproximaciones Terapéuticas y Traslación Clínica de los Resultados” from the Instituto de Salud Carlos III. IS and ALA were supported by the Agustín de Betancourt Programme. JEP was supported by Ayudas Plan Propio de la Universidad de La Laguna 2018 (proyectos puente I+D+i).
Sifaoui I, Martín-Navarro CM, López-Arencibia A, Reyes-Batlle M, Valladares B, Piñero JE, et al. Optimized combinations of statins and azoles against Acanthamoeba trophozoites and cysts in vitro. Asian Pac J Trop Med 2019; 12(6): 283-287.