Vernonia brasiliana (L.) Druce induces ultrastructural changes and apoptosis-like death of Leishmania infantum promastigotes.

Autor: Mondêgo-Oliveira R; Rede Nordeste de Biotecnologia, Universidade Federal do Maranhão, 65080-805, São Luís, Maranhão, Brazil. Electronic address: re_mondego@hotmail.com., de Sá Sousa JC; Universidade CEUMA, 65075-120, São Luís, Maranhão, Brazil. Electronic address: joicyvet@hotmail.com., Moragas-Tellis CJ; Laboratório de Produtos Naturais para Saúde Pública (LPNSP), Instituto de Tecnologia em Fármacos - Farmanguinhos, Fiocruz, 21041-000, Rio de Janeiro, Brazil. Electronic address: carla.tellis@far.fiocruz.br., de Souza PVR; Laboratório de Produtos Naturais para Saúde Pública (LPNSP), Instituto de Tecnologia em Fármacos - Farmanguinhos, Fiocruz, 21041-000, Rio de Janeiro, Brazil; Programa de Pós Graduação Acadêmico em Pesquisa Translacional em Fármacos e Medicamentos, Instituto de Tecnologia em Fármacos - Farmanguinhos, Fiocruz, 21041-000, Rio de Janeiro, Brazil. Electronic address: pvrs.pvrs@gmail.com., Dos Santos Chagas MDS; Laboratório de Produtos Naturais para Saúde Pública (LPNSP), Instituto de Tecnologia em Fármacos - Farmanguinhos, Fiocruz, 21041-000, Rio de Janeiro, Brazil. Electronic address: msocchagas@gmail.com., Behrens MD; Laboratório de Produtos Naturais para Saúde Pública (LPNSP), Instituto de Tecnologia em Fármacos - Farmanguinhos, Fiocruz, 21041-000, Rio de Janeiro, Brazil. Electronic address: mariabehrens@hotmail.com., Jesús Hardoim D; Laboratório de Imunomodulação e Protozoologia, Instituto Oswaldo Cruz, Fiocruz, 21040-900, Rio de Janeiro, Brazil. Electronic address: hardoim@ioc.fiocruz.br., Taniwaki NN; Núcleo de Microscopia Eletrônica, Instituto Adolfo Lutz, 01246-000, São Paulo, Brazil. Electronic address: ntaniwak@hotmail.com., Chometon TQ; Plataforma Tecnológica de Citometria de Fluxo, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. Electronic address: thaizeqcp@gmail.com., Bertho AL; Laboratório de Imunoparasitologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. Electronic address: alvaro.bertho@ioc.fiocruz.br., Calabrese KDS; Laboratório de Imunomodulação e Protozoologia, Instituto Oswaldo Cruz, Fiocruz, 21040-900, Rio de Janeiro, Brazil. Electronic address: calabrese@ioc.fiocruz.br., Almeida-Souza F; Laboratório de Imunomodulação e Protozoologia, Instituto Oswaldo Cruz, Fiocruz, 21040-900, Rio de Janeiro, Brazil; Universidade Estadual do Maranhão, 65055-310, São Luís, Maranhão, Brazil. Electronic address: fernandoalsouza@gmail.com., Abreu-Silva AL; Rede Nordeste de Biotecnologia, Universidade Federal do Maranhão, 65080-805, São Luís, Maranhão, Brazil; Universidade Estadual do Maranhão, 65055-310, São Luís, Maranhão, Brazil. Electronic address: abreusilva.ana@gmail.com.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2021 Jan; Vol. 133, pp. 111025. Date of Electronic Publication: 2020 Nov 27.
DOI: 10.1016/j.biopha.2020.111025
Abstrakt: The present study aimed to evaluate the antileishmanial effect, the mechanisms of action and the association with miltefosine of Vernonia brasiliana essential oil against Leishmania infantum promastigotes. This essential oil was obtained by hydrodistillation and its chemical composition was determined by gas chromatography-mass spectrometry (GC-MS). The antileishmanial activity against L. infantum promastigotes and cytotoxicity on DH82 cells were evaluated by MTT colorimetric assay. Ultrastructural alterations were evaluated by transmission electron microscopy. Changes in mitochondrial membrane potential, in the production of reactive oxygen species, and analysis of apoptotic events were determined by flow cytometry. The association between the essential oil and miltefosine was evaluated using the modified isobologram method. The most abundant component of the essential oil was β-caryophyllene (21.47 %). Anti-Leishmania assays indicated an IC 50 of 39.01 ± 1.080 μg/mL for promastigote forms after 72 h of treatment. The cytotoxic concentration for DH82 cells was 63.13 ± 1.211 μg/mL after 24 h of treatment. The effect against L. infantum was proven through the ultrastructural changes caused by the oil, such as kinetoplast and mitochondrial swelling, vesicles in the flagellar pocket, discontinuity of the nuclear membrane, nuclear fragmentation and condensation, and loss of organelles. It was observed that the oil leads to a decrease in the mitochondrial membrane potential (35.10 %, p = 0.0031), increased reactive oxygen species production, and cell death by late apoptosis (17.60 %, p = 0.020). The combination of the essential oil and miltefosine exhibited an antagonistic effect. This study evidences the antileishmanial action of V. brasiliana essential oil against L. infantum promastigotes.
(Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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