Freitas, Camila Simões deLage, Daniela PagliaraSilva, João Augusto Oliveira daCosta, Rafaella RodriguesMendonça, Débora Vasconcelos CostaMartins, Vívian TamiettiReis, Thiago Alves Rosa dosAntinarelli, Luciana Maria RibeiroMachado, Amanda SanchezTavares, Grasiele de Sousa VieiraRamos, Fernanda FonsecaBrito, Rory Cristiane Fortes deRibeiro, Fernanda LudolfChávez Fumagalli, Miguel AngelRoatt, Bruno MendesRamos, Gabriela S.Munkert, JenniferOttoni, Flaviano MeloCampana, Priscilla Rodrigues ValadaresDuarte, Mariana CostaGonçalves, Denise UtschCoimbra, Elaine SoaresBraga, Fernão CastroPádua, Rodrigo Maia deCoelho, Eduardo Antônio Ferraz2021-09-302021-09-302021FREITAS, C. S. de et al. In vitro and in vivo antileishmanial activity of b-acetyl-digitoxin, a cardenolide of Digitalis lanata potentially useful to treat visceral leishmaniasis. Parasite, v. 28, artigo 38, abr. 2021. Disponível em: <https://www.parasite-journal.org/articles/parasite/full_html/2021/01/parasite200128/parasite200128.html>. Acesso em: 10 jun. 2021.1776-1042http://www.repositorio.ufop.br/jspui/handle/123456789/13834Current 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 b-acetyl-digitoxin (b-AD), a cardenolide isolated from Digitalis lanata leaves, assayed in vitro and in vivo against Leishmania infantum. Results showed direct action of b-AD against parasites, as well as efficacy for the treatment of Leishmania-infected macrophages. In vivo experiments 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-c, IL-12, TNF-a, GM-CSF, nitrite and specific IgG2a antibodies, in addition to low IL-4 and IL-10 contents, along with higher IFN-c-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.en-USabertoDrug repositioningToxicityMiltefosineArtigo publicado em periodicoThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Fonte: o PDF do artigo.https://doi.org/10.1051/parasite/2021036