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Title: Ivermectin presents effective and selective antileishmanial activity in vitro and in vivo against Leishmania infantum and is therapeutic against visceral leishmaniasis.
Authors: Reis, Thiago Alves Rosa dos
Silva, João Augusto Oliveira da
Tavares, Grasiele de Sousa Vieira
Mendonça, Débora Vasconcelos Costa
Freitas, Camila Simões de
Costa, Rafaella Rodrigues
Lage, Daniela Pagliara
Martins, Vívian Tamietti
Machado, Amanda Sanchez
Ramos, Fernanda Fonseca
Silva, Alessandra M.
Ribeiro, Fernanda Ludolf
Antinarelli, Luciana Maria Ribeiro
Brito, Rory Cristiane Fortes de
Chávez Fumagalli, Miguel Angel
Humbert, Maria Victoria
Roatt, Bruno Mendes
Coimbra, Elaine Soares
Coelho, Eduardo Antônio Ferraz
Keywords: Drug repositioning
Issue Date: 2021
Citation: REIS, T. A. R. dos et al. Ivermectin presents effective and selective antileishmanial activity in vitro and in vivo against Leishmania infantum and is therapeutic against visceral leishmaniasis. Experimental Parasitology, v. 221, artigo 108059, fev. 2021. Disponível em: <>. Acesso em: 10 jun. 2021.
Abstract: Treatment 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.
ISSN: 0014-4894
Appears in Collections:DECBI - Artigos publicados em periódicos

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