| Autor: |
Freitas, Camila S., Lage, Daniela P., Oliveira-da-Silva, João A., Costa, Rafaella R., Mendonça, Débora V.C., Martins, Vívian T., Reis, Thiago A.R., Antinarelli, Luciana M.R., Machado, Amanda S., Tavares, Grasiele S.V., Ramos, Fernanda F., Brito, Rory C.F., Ludolf, Fernanda, Chávez-Fumagalli, Miguel A., Roatt, Bruno M., Ramos, Gabriela S., Munkert, Jennifer, Ottoni, Flaviano M., Campana, Priscilla R.V., Duarte, Mariana C., Gonçalves, Denise U., Coimbra, Elaine S., Braga, Fernão C., Pádua, Rodrigo M., Coelho, Eduardo A.F., Freitas, Camila S., Lage, Daniela P., Oliveira-da-Silva, João A., Costa, Rafaella R., Mendonça, Débora V.C., Martins, Vívian T., Reis, Thiago A.R., Antinarelli, Luciana M.R., Machado, Amanda S., Tavares, Grasiele S.V., Ramos, Fernanda F., Brito, Rory C.F., Ludolf, Fernanda, Chávez-Fumagalli, Miguel A., Roatt, Bruno M., Ramos, Gabriela S., Munkert, Jennifer, Ottoni, Flaviano M., Campana, Priscilla R.V., Duarte, Mariana C., Gonçalves, Denise U., Coimbra, Elaine S., Braga, Fernão C., Pádua, Rodrigo M., Coelho, Eduardo A.F. |
| Zdroj: |
Parasite - Journal de la Société Française de Parasitologie; January 2021, Vol. 28 Issue: 1 |
| Abstrakt: |
Current treatments of visceral leishmaniasis face limitations due to drug side effects and/or high cost, along with the emergence of parasite resistance. Novel and low-cost antileishmanial agents are therefore required. We report herein the antileishmanial activity of β-acetyl-digitoxin (b-AD), a cardenolide isolated from Digitalis lanataleaves, assayed in vitroand in vivoagainst Leishmania infantum. Results showed direct action of b-AD against parasites, as well as efficacy for the treatment of Leishmania-infected macrophages. In vivoexperiments using b-AD-containing Pluronic®F127 polymeric micelles (b-AD/Mic) to treat L. infantum-infected mice showed that this composition reduced the parasite load in distinct organs in more significant levels. It also induced the development of anti-parasite Th1-type immunity, attested by high levels of IFN-γ, IL-12, TNF-α, GM-CSF, nitrite and specific IgG2a antibodies, in addition to low IL-4 and IL-10 contents, along with higher IFN-γ-producing CD4+and CD8+T-cell frequency. Furthermore, low toxicity was found in the organs of the treated animals. Comparing the therapeutic effect between the treatments, b-AD/Mic was the most effective in protecting animals against infection, when compared to the other groups including miltefosine used as a drug control. Data found 15 days after treatment were similar to those obtained one day post-therapy. In conclusion, the results obtained suggest that b-AD/Mic is a promising antileishmanial agent and deserves further studies to investigate its potential to treat visceral leishmaniasis. |
| Databáze: |
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