Trypanosoma cruzi mitochondrial swelling and membrane potential collapse as primary evidence of the mode of action of naphthoquinone analogues

Detalhes bibliográficos
Autor(a) principal: Salomão, Kelly
Data de Publicação: 2013
Outros Autores: Santana, Natalia A. de, Molina, Maria Teresa, Castro, Solange L. de, Menna-Barreto, Rubem F. S.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/15954
Resumo: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.
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spelling Salomão, KellySantana, Natalia A. deMolina, Maria TeresaCastro, Solange L. deMenna-Barreto, Rubem F. S.2016-09-27T11:13:29Z2016-09-27T11:13:29Z2013SALOMÃO, Kelly; et al. Trypanosoma cruzi mitochondrial swelling and membrane potential collapse as primary evidence of the mode of action of naphthoquinone analogues. BMC Microbiology, v,13, n.196, 12p, 2013.1471-2180https://www.arca.fiocruz.br/handle/icict/1595410.1186/1471-2180-13-196engBioMed CentralTrypanosoma cruziQuimioterapiaNaftoquinonasMitocôndriasTrypanosoma cruziNaphthoquinonesJugloneExperimental chemotherapyMitochondriaTrypanosoma cruzi mitochondrial swelling and membrane potential collapse as primary evidence of the mode of action of naphthoquinone analoguesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.CSIC. Instituto de Química Médica. JUan de la Cierva, Madrid, Spain.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Background: Naphthoquinones (NQs) are privileged structures in medicinal chemistry due to the biological effects associated with the induction of oxidative stress. The present study evaluated the activities of sixteen NQs derivatives on Trypanosoma cruzi. Results: Fourteen NQs displayed higher activity against bloodstream trypomastigotes of T. cruzi than benznidazole. Further assays with NQ1, NQ8, NQ9 and NQ12 showed inhibition of the proliferation of axenic epimastigotes and intracelulluar amastigotes interiorized in macrophages and in heart muscle cells. NQ8 was the most active NQ against both proliferative forms of T. cruzi. In epimastigotes the four NQs induced mitochondrial swelling, vacuolization, and flagellar blebbing. The treatment with NQs also induced the appearance of large endoplasmic reticulum profiles surrounding different cellular structures and of myelin-like membranous contours, morphological characteristics of an autophagic process. At IC50 concentration, NQ8 totally disrupted the ΔΨm of about 20% of the parasites, suggesting the induction of a sub-population with metabolically inactive mitochondria. On the other hand, NQ1, NQ9 or NQ12 led only to a discrete decrease of TMRE + labeling at IC50 values. NQ8 led also to an increase in the percentage of parasites labeled with DHE, indicative of ROS production, possibly the cause of the observed mitochondrial swelling. The other three NQs behaved similarly to untreated controls. Conclusions: NQ1, NQ8, NQ9 and NQ12 induce an autophagic phenotype in T. cruzi epimastigoted, as already observed with others NQs. The absence of oxidative stress in NQ1-, NQ9- and NQ12-treated parasites could be due to the existence of more than one mechanism of action involved in their trypanocidal activity, leaving ROS generation suppressed by the detoxification system of the parasite. The strong redox effect of NQ8 could be associated to the presence of the acetyl group in its structure facilitating quinone reduction, as previously demonstrated by electrochemical analysis. Further experiments using biochemical and molecular approaches are needed to better characterize ROS participation in the mechanism of action of these NQs.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/15954/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALkelly_salomao_etal_IOC_2013.pdfkelly_salomao_etal_IOC_2013.pdfapplication/pdf3126593https://www.arca.fiocruz.br/bitstream/icict/15954/2/kelly_salomao_etal_IOC_2013.pdf06ebb16ffb2888ea03347c365034a854MD52TEXTkelly_salomao_etal_IOC_2013.pdf.txtkelly_salomao_etal_IOC_2013.pdf.txtExtracted texttext/plain47667https://www.arca.fiocruz.br/bitstream/icict/15954/3/kelly_salomao_etal_IOC_2013.pdf.txtbd7c9d1919fad46b5d6b37293df1c1b3MD53icict/159542018-04-02 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dc.title.pt_BR.fl_str_mv Trypanosoma cruzi mitochondrial swelling and membrane potential collapse as primary evidence of the mode of action of naphthoquinone analogues
title Trypanosoma cruzi mitochondrial swelling and membrane potential collapse as primary evidence of the mode of action of naphthoquinone analogues
spellingShingle Trypanosoma cruzi mitochondrial swelling and membrane potential collapse as primary evidence of the mode of action of naphthoquinone analogues
Salomão, Kelly
Trypanosoma cruzi
Quimioterapia
Naftoquinonas
Mitocôndrias
Trypanosoma cruzi
Naphthoquinones
Juglone
Experimental chemotherapy
Mitochondria
title_short Trypanosoma cruzi mitochondrial swelling and membrane potential collapse as primary evidence of the mode of action of naphthoquinone analogues
title_full Trypanosoma cruzi mitochondrial swelling and membrane potential collapse as primary evidence of the mode of action of naphthoquinone analogues
title_fullStr Trypanosoma cruzi mitochondrial swelling and membrane potential collapse as primary evidence of the mode of action of naphthoquinone analogues
title_full_unstemmed Trypanosoma cruzi mitochondrial swelling and membrane potential collapse as primary evidence of the mode of action of naphthoquinone analogues
title_sort Trypanosoma cruzi mitochondrial swelling and membrane potential collapse as primary evidence of the mode of action of naphthoquinone analogues
author Salomão, Kelly
author_facet Salomão, Kelly
Santana, Natalia A. de
Molina, Maria Teresa
Castro, Solange L. de
Menna-Barreto, Rubem F. S.
author_role author
author2 Santana, Natalia A. de
Molina, Maria Teresa
Castro, Solange L. de
Menna-Barreto, Rubem F. S.
author2_role author
author
author
author
dc.contributor.author.fl_str_mv Salomão, Kelly
Santana, Natalia A. de
Molina, Maria Teresa
Castro, Solange L. de
Menna-Barreto, Rubem F. S.
dc.subject.other.pt_BR.fl_str_mv Trypanosoma cruzi
Quimioterapia
Naftoquinonas
Mitocôndrias
topic Trypanosoma cruzi
Quimioterapia
Naftoquinonas
Mitocôndrias
Trypanosoma cruzi
Naphthoquinones
Juglone
Experimental chemotherapy
Mitochondria
dc.subject.en.pt_BR.fl_str_mv Trypanosoma cruzi
Naphthoquinones
Juglone
Experimental chemotherapy
Mitochondria
description Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.
publishDate 2013
dc.date.issued.fl_str_mv 2013
dc.date.accessioned.fl_str_mv 2016-09-27T11:13:29Z
dc.date.available.fl_str_mv 2016-09-27T11:13:29Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv SALOMÃO, Kelly; et al. Trypanosoma cruzi mitochondrial swelling and membrane potential collapse as primary evidence of the mode of action of naphthoquinone analogues. BMC Microbiology, v,13, n.196, 12p, 2013.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/15954
dc.identifier.issn.pt_BR.fl_str_mv 1471-2180
dc.identifier.doi.none.fl_str_mv 10.1186/1471-2180-13-196
identifier_str_mv SALOMÃO, Kelly; et al. Trypanosoma cruzi mitochondrial swelling and membrane potential collapse as primary evidence of the mode of action of naphthoquinone analogues. BMC Microbiology, v,13, n.196, 12p, 2013.
1471-2180
10.1186/1471-2180-13-196
url https://www.arca.fiocruz.br/handle/icict/15954
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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https://www.arca.fiocruz.br/bitstream/icict/15954/2/kelly_salomao_etal_IOC_2013.pdf
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