Ivermectin presents effective and selective antileishmanial activity in vitro and in vivo against Leishmania infantum and is therapeutic against visceral leishmaniasis.

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MetadadosDescriçãoIdioma
Autor(es): dc.creatorReis, Thiago Alves Rosa dos-
Autor(es): dc.creatorSilva, João Augusto Oliveira da-
Autor(es): dc.creatorTavares, Grasiele de Sousa Vieira-
Autor(es): dc.creatorMendonça, Débora Vasconcelos Costa-
Autor(es): dc.creatorFreitas, Camila Simões de-
Autor(es): dc.creatorCosta, Rafaella Rodrigues-
Autor(es): dc.creatorLage, Daniela Pagliara-
Autor(es): dc.creatorMartins, Vívian Tamietti-
Autor(es): dc.creatorMachado, Amanda Sanchez-
Autor(es): dc.creatorRamos, Fernanda Fonseca-
Autor(es): dc.creatorSilva, Alessandra M.-
Autor(es): dc.creatorRibeiro, Fernanda Ludolf-
Autor(es): dc.creatorAntinarelli, Luciana Maria Ribeiro-
Autor(es): dc.creatorBrito, Rory Cristiane Fortes de-
Autor(es): dc.creatorChávez Fumagalli, Miguel Angel-
Autor(es): dc.creatorHumbert, Maria Victoria-
Autor(es): dc.creatorRoatt, Bruno Mendes-
Autor(es): dc.creatorCoimbra, Elaine Soares-
Autor(es): dc.creatorCoelho, Eduardo Antônio Ferraz-
Data de aceite: dc.date.accessioned2025-08-21T15:31:01Z-
Data de disponibilização: dc.date.available2025-08-21T15:31:01Z-
Data de envio: dc.date.issued2021-09-30-
Data de envio: dc.date.issued2021-09-30-
Data de envio: dc.date.issued2020-
Fonte completa do material: dc.identifierhttp://www.repositorio.ufop.br/jspui/handle/123456789/13835-
Fonte completa do material: dc.identifierhttps://www.sciencedirect.com/science/article/abs/pii/S0014489420305841-
Fonte completa do material: dc.identifierhttps://doi.org/10.1016/j.exppara.2020.108059-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/capes/1017196-
Descrição: dc.descriptionTreatment for visceral leishmaniasis (VL) is hindered mainly by the toxicity and/or high cost of therapeutic drugs. In addition, parasite resistance has been registered. Thus, there is an urgent need for the identification of novel, effective and low-cost antileishmanial agents. Since drug discovery is a long and expensive process, drug repositioning for treatment of leishmaniasis should be considered. In the present study, Ivermectin (IVE), a broad-spectrum drug used for treatment of parasitic diseases, was evaluated in vitro and in vivo against Leishmania infantum species. Results in vitro showed that IVE presented 50% Leishmania and macrophage inhibitory concentrations (IC50 and CC50, respectively) of 3.64 ± 0.48 μM and 427.50 ± 17.60 μM, respectively, with a selectivity index (SI) of 117.45; whereas Amphotericin B (AmpB), which was used as control, showed IC50 and CC50 values of 0.12 ± 0.05 μM and 1.06 ± 0.23 μM, respectively, with a corresponding SI of 8.90. Treatment with IVE effectively reduced the infection percentage and parasite burden in infected and treated macrophages and displayed a prophylactic activity by inhibiting macrophage infection with pre-treated parasites. Furthermore, preliminary studies suggested that IVE targets the parasite’s mitochondria. Activity of IVE in its free format or incorporated into Pluronic® F127-based polymeric micelles (IVE/Mic) was also evaluated in vivo as a treating drug for L. infantum-infected BALB/c mice. Miltefosine was used as a control. Results showed that Miltefosine, IVE and IVE/Mic-treated animals presented significant reductions in the parasite load in their spleens, livers, bone marrows and draining lymph nodes, as well as development of an antileishmanial Th1-type immune response one and 15 days after treatment. Notably, IVE/Mic showed a better parasitological and immunological response in comparison to other alternative treatments. In conclusion, results suggest that IVE/Mic could be considered in future studies as a therapeutic alternative to treat VL.-
Formato: dc.formatapplication/pdf-
Idioma: dc.languageen-
Direitos: dc.rightsrestrito-
Palavras-chave: dc.subjectDrug repositioning-
Palavras-chave: dc.subjectTreatment-
Palavras-chave: dc.subjectMiltefosine-
Título: dc.titleIvermectin presents effective and selective antileishmanial activity in vitro and in vivo against Leishmania infantum and is therapeutic against visceral leishmaniasis.-
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