Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/7917
Title: Activity of antimalarial drugs in vitro and in a murine model of cutaneous leishmaniasis
Authors: Rocha, Vinícius Pinto Costa
Nonato, Fabiana Regina
Guimarães, Elisalva Teixeira
Freitas, Luiz Antonio Rodrigues de
Soares, Milena Botelho Pereira
Affilliation: Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, Brasil / Universidade do Estado da Bahia. Departamento de Ciências da Vida. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Patologia e Biointervenção. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina da Bahia. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil.
Abstract: The currently used treatments for leishmaniasis, a neglected parasitic disease, are associated with several side effects, high cost and resistance of the Leishmania parasites. Here we evaluated in vitro and in vivo the antileishmanial activity of five antimalarial drugs against Leishmania amazonensis. Mefloquine was effective against promastigotes in axenic cultures and showed an IC50 (concentration giving half-maximal inhibition) value of 8.4±0.7 mM. In addition, mefloquine, chloroquine and hydroxychloroquine were active against intracellular amastigotes in macrophageinfected cultures, presenting IC50 values of 1.56±0.19 mM, 0.78±0.08 mM and 0.67±0.12 mM, respectively. The ultrastructural analysis of chloroquine- or mefloquine-treated amastigotes showed an accumulation of multivesicular bodies in the cytoplasm of the parasite, suggesting endocytic pathway impairment, in addition to the formation of myelin-like figures and enlargement of the Golgi cisternae. CBA mice were infected with L. amazonensis in the ear dermis, and treated by oral and/or topical routes with chloroquine and mefloquine. Treatment of L. amazonensisinfected mice with chloroquine by the oral route reduced lesion size, which was associated with a decrease in the number of parasites in the ear, as well as the parasite burden in the draining lymph nodes. In contrast, mefloquine administration by both routes decreased the lesion size in infected mice without causing a reduction in parasite burden. Our results revealed a promising antileishmanial effect of chloroquine and suggest its use in cutaneous leishmaniasis treatment.
keywords: Antimaláricos
Farmacologia
Leishmaniose Cutânea
Efeitos de drogas
Parasitologia
DeCS: Antimaláricos/farmacologia
Antimaláricos/uso terapêutico
Leishmania mexicana/efeitos de drogas
Leishmaniose Cutânea/quimioterapia
Animais
Feminino
Concentração Inibidora 50
Leishmaniose Cutânea/parasitologia
Macrófagos
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Endogâmicos CBA
Issue Date: 2013
Publisher: Society for General Microbiology
Citation: ROCHA, V. P. C. et al. Activity of antimalarial drugs in vitro and in a murine model of cutaneous leishmaniasis. Journal of Medical Microbiology, v. 62, n. 7, p. 1001-1010, 2013.
DOI: 10.1099/jmm.0.058115-0
ISSN: 1473-5644
Copyright: restricted access
Appears in Collections:BA - IGM - Artigos de Periódicos

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