Efficacy of different nitric oxide-based strategies in preventing experimental cerebral malaria by Plasmodium berghei ANKA

Detalhes bibliográficos
Autor(a) principal: Martins, Yuri C.
Data de Publicação: 2012
Outros Autores: Zanini, Graziela M., Frangos, John A., Carvalho, Leonardo J. M.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/18496
Resumo: La Jolla Bioengineering Institute. Center for Malaria Research. San Diego, CA, USA / Universidade Federal do Rio de Janeiro. Laboratório de Inflamação e Imunidade. Rio de Janeiro, RJ, Brasil.
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spelling Martins, Yuri C.Zanini, Graziela M.Frangos, John A.Carvalho, Leonardo J. M.2017-04-18T15:42:36Z2017-04-18T15:42:36Z2012MARTINS, Yuri C. et al. Efficacy of Different Nitric Oxide-Based Strategies in Preventing Experimental Cerebral Malaria by Plasmodium berghei ANKA. Plos One, v. 7, n. 2, p. 1-10, Feb. 2012.1932-6203https://www.arca.fiocruz.br/handle/icict/1849610.1371/journal.pone.0032048engPublic Library of ScienceMalária cerebralÓxido nítricoPlasmodium bergheiPrevençãoCerebral MalariaNitric OxidePlasmodium bergheiPreventing ExperimentalEfficacy of different nitric oxide-based strategies in preventing experimental cerebral malaria by Plasmodium berghei ANKAinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleLa Jolla Bioengineering Institute. Center for Malaria Research. San Diego, CA, USA / Universidade Federal do Rio de Janeiro. Laboratório de Inflamação e Imunidade. Rio de Janeiro, RJ, Brasil.La Jolla Bioengineering Institute. Center for Malaria Research. San Diego, CA, USA / Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Serviço de Parasitologia. Rio de Janeiro, RJ, Brasil.La Jolla Bioengineering Institute. Center for Malaria Research. San Diego, CA, USA.La Jolla Bioengineering Institute. Center for Malaria Research. San Diego, CA, USA / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Malária. Rio de Janeiro, RJ, Brasil.Background: Low nitric oxide (NO) bioavailability plays a role in the pathogenesis of human as well as of experimental cerebral malaria (ECM) caused by Plasmodium berghei ANKA (PbA). ECM is partially prevented by administration of the NOdonor dipropylenetriamine NONOate (DPTA-NO) at high concentration (1 mg/mouse), which also induces major side effects such as a sharp drop in blood pressure. We asked whether alternative strategies to improve NO bioavailability with minor side effects would also be effective in preventing ECM. Methodology/Principal Findings: Mice were infected with PbA and prophylactically treated twice a day with bolus injections of L-arginine, Nv-hydroxy-nor-Arginine (nor-NOHA), tetrahydrobiopterin (BH4), separately or combined, sodium nitrite, sildenafil or sildenafil plus DPTA-NO starting on day 0 of infection. L-arginine and BH4 supplementation, with or without arginase inhibition by nor-NOHA, increased plasma nitrite levels but failed to protect against ECM development. Accordingly, prophylactic treatment with continuous delivery of L-arginine using osmotic pumps also did not improve survival. Similar outcomes were observed with sodium nitrite sildenafil (aimed at inhibiting hosphodiesterase-5) or with DPTA-NO. However, sildenafil (0.1 mg/mouse) in combination with a lower dose (0.1 mg/mouse) of DPTA-NO decreased ECM incidence (8267.4% mortality in the saline group and 38610.6% in the treated group; p,0.05). The combined prophylactic therapy did not aggravate anemia, had delayed effects in systolic, diastolic and mean arterial blood pressure and induced lower effects in pulse pressure when compared to DPTA-NO 1 mg/mouse. Conclusions/Significance: These data show that sildenafil lowers the amount of NO-donor needed to prevent ECM, resulting also in lesser side effects. Prophylactic L-arginine when given in bolus or continuous delivery and bolus BH4 supplementation, with or without arginase inhibition, were able to increase NO bioavailability in PbA-infected mice but failed to decrease ECM incidence in the doses and protocol used.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/18496/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALleonardo2_carvalho_etal_IOC_2012.pdfleonardo2_carvalho_etal_IOC_2012.pdfapplication/pdf999955https://www.arca.fiocruz.br/bitstream/icict/18496/2/leonardo2_carvalho_etal_IOC_2012.pdfc33bcd75b4b7eab314cad46f4da7ddb3MD52TEXTleonardo2_carvalho_etal_IOC_2012.pdf.txtleonardo2_carvalho_etal_IOC_2012.pdf.txtExtracted 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dc.title.pt_BR.fl_str_mv Efficacy of different nitric oxide-based strategies in preventing experimental cerebral malaria by Plasmodium berghei ANKA
title Efficacy of different nitric oxide-based strategies in preventing experimental cerebral malaria by Plasmodium berghei ANKA
spellingShingle Efficacy of different nitric oxide-based strategies in preventing experimental cerebral malaria by Plasmodium berghei ANKA
Martins, Yuri C.
Malária cerebral
Óxido nítrico
Plasmodium berghei
Prevenção
Cerebral Malaria
Nitric Oxide
Plasmodium berghei
Preventing Experimental
title_short Efficacy of different nitric oxide-based strategies in preventing experimental cerebral malaria by Plasmodium berghei ANKA
title_full Efficacy of different nitric oxide-based strategies in preventing experimental cerebral malaria by Plasmodium berghei ANKA
title_fullStr Efficacy of different nitric oxide-based strategies in preventing experimental cerebral malaria by Plasmodium berghei ANKA
title_full_unstemmed Efficacy of different nitric oxide-based strategies in preventing experimental cerebral malaria by Plasmodium berghei ANKA
title_sort Efficacy of different nitric oxide-based strategies in preventing experimental cerebral malaria by Plasmodium berghei ANKA
author Martins, Yuri C.
author_facet Martins, Yuri C.
Zanini, Graziela M.
Frangos, John A.
Carvalho, Leonardo J. M.
author_role author
author2 Zanini, Graziela M.
Frangos, John A.
Carvalho, Leonardo J. M.
author2_role author
author
author
dc.contributor.author.fl_str_mv Martins, Yuri C.
Zanini, Graziela M.
Frangos, John A.
Carvalho, Leonardo J. M.
dc.subject.other.pt_BR.fl_str_mv Malária cerebral
Óxido nítrico
Plasmodium berghei
Prevenção
topic Malária cerebral
Óxido nítrico
Plasmodium berghei
Prevenção
Cerebral Malaria
Nitric Oxide
Plasmodium berghei
Preventing Experimental
dc.subject.en.pt_BR.fl_str_mv Cerebral Malaria
Nitric Oxide
Plasmodium berghei
Preventing Experimental
description La Jolla Bioengineering Institute. Center for Malaria Research. San Diego, CA, USA / Universidade Federal do Rio de Janeiro. Laboratório de Inflamação e Imunidade. Rio de Janeiro, RJ, Brasil.
publishDate 2012
dc.date.issued.fl_str_mv 2012
dc.date.accessioned.fl_str_mv 2017-04-18T15:42:36Z
dc.date.available.fl_str_mv 2017-04-18T15:42:36Z
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 MARTINS, Yuri C. et al. Efficacy of Different Nitric Oxide-Based Strategies in Preventing Experimental Cerebral Malaria by Plasmodium berghei ANKA. Plos One, v. 7, n. 2, p. 1-10, Feb. 2012.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/18496
dc.identifier.issn.pt_BR.fl_str_mv 1932-6203
dc.identifier.doi.none.fl_str_mv 10.1371/journal.pone.0032048
identifier_str_mv MARTINS, Yuri C. et al. Efficacy of Different Nitric Oxide-Based Strategies in Preventing Experimental Cerebral Malaria by Plasmodium berghei ANKA. Plos One, v. 7, n. 2, p. 1-10, Feb. 2012.
1932-6203
10.1371/journal.pone.0032048
url https://www.arca.fiocruz.br/handle/icict/18496
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 Public Library of Science
publisher.none.fl_str_mv Public Library of Science
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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