Use este identificador para citar ou linkar para este item: http://www.repositorio.ufop.br/jspui/handle/123456789/13816
Título: Digitoxigenin presents an effective and selective antileishmanial action against Leishmania infantum and is a potential therapeutic agent for visceral leishmaniasis.
Autor(es): Freitas, Camila Simões de
Silva, João Augusto Oliveira da
Lage, Daniela Pagliara
Costa, Rafaella Rodrigues
Mendonça, Débora Vasconcelos Costa
Martins, Vívian Tamietti
Reis, Thiago Alves Rosa dos
Antinarelli, Luciana Maria Ribeiro
Machado, Amanda Sanchez
Tavares, Grasiele de Sousa Vieira
Ramos, Fernanda Fonseca
Coelho, Vinicio Tadeu da Silva
Brito, Rory Cristiane Fortes de
Ribeiro, Fernanda Ludolf
Chávez Fumagalli, Miguel Angel
Roatt, Bruno Mendes
Ramos, Gabriela S.
Munkert, Jennifer
Ottoni, Flaviano Melo
Campana, Priscilla Rodrigues Valadares
Humbert, Maria Victoria
Coimbra, Elaine Soares
Braga, Fernão Castro
Pádua, Rodrigo Maia de
Coelho, Eduardo Antônio Ferraz
Palavras-chave: Treatment
Drug repositioning
Amphotericin B deoxycholate
Miltefosine
Data do documento: 2020
Referência: FREITAS, C. S. de et al. Digitoxigenin presents an effective and selective antileishmanial action against Leishmania infantum and is a potential therapeutic agent for visceral leishmaniasis. Parasitology Research v. 120, p. 321-335, 2020. Disponível em: <https://link.springer.com/article/10.1007/s00436-020-06971-2>. Acesso em: 10 jun. 2021.
Resumo: Treatment for visceral leishmaniasis (VL) is hampered mainly by drug toxicity, their high cost, and parasite resistance. Drug development is a long and pricey process, and therefore, drug repositioning may be an alternative worth pursuing. Cardenolides are used to treat cardiac diseases, especially those obtained from Digitalis species. In the present study, cardenolide digitoxigenin (DIGI) obtained from a methanolic extract of Digitalis lanata leaves was tested for its antileishmanial activity against Leishmania infantum species. Results showed that 50% Leishmania and murine macrophage inhibitory concentrations (IC50 and CC50, respectively) were of 6.9 ± 1.5 and 295.3 ± 14.5 μg/mL, respectively. With amphotericin B (AmpB) deoxycholate, used as a control drug, values of 0.13 ± 0.02 and 0.79 ± 0.12 μg/mL, respectively, were observed. Selectivity index (SI) values were of 42.8 and 6.1 for DIGI and AmpB, respectively. Preliminary studies suggested that the mechanism of action for DIGI is to cause alterations in the mitochondrial membrane potential, to increase the levels of reactive oxygen species and induce accumulation of lipid bodies in the parasites. DIGI was incorporated into Pluronic® F127-based polymeric micelles, and the formula (DIGI/Mic) was used to treat L. infantum–infected mice. Miltefosine was used as a control drug. Results showed that animals treated with either miltefosine, DIGI, or DIGI/Mic presented significant reductions in the parasite load in their spleens, livers, bone marrows, and draining lymph nodes, as well as the development of a specific Th1-type response, when compared with the controls. Results obtained 1 day after treatment were corroborated with data corresponding to 15 days after therapy. Importantly, treatment with DIGI/Mic induced better parasitological and immunological responses when compared with miltefosine- and DIGI-treated mice. In conclusion, DIGI/Mic has the potential to be used as a therapeutic agent to protect against L. infantum infection, and it is therefore worth of consideration in future studies addressing VL treatment.
URI: http://www.repositorio.ufop.br/jspui/handle/123456789/13816
Link para o artigo: https://link.springer.com/article/10.1007/s00436-020-06971-2
DOI: https://doi.org/10.1007/s00436-020-06971-2
ISSN: 1432-1955
Aparece nas coleções:DECBI - Artigos publicados em periódicos

Arquivos associados a este item:
Arquivo Descrição TamanhoFormato 
ARTIGO_DigitoxigeninPresentsEffective.pdf
  Restricted Access
2,04 MBAdobe PDFVisualizar/Abrir


Os itens no repositório estão protegidos por copyright, com todos os direitos reservados, salvo quando é indicado o contrário.