Acetylsalicylic acid and combined therapy with dihydroartemisinin modulate lung injury on experimental malaria-associated ARDS

Detalhes bibliográficos
Autor(a) principal: Oliveira, Helena D'Anunciação de
Data de Publicação: 2019
Outros Autores: Batista, Camila Nunes, Lima, Maiara Nascimento de, Silva, Adriano Yagho da, Rocco, Patricia Rieken Macedo, Faria-Neto, Hugo Caire de Castro, Maron-Gutierrez, Tatiana
Tipo de documento: Artigo de conferência
Idioma: por
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/60211
Resumo: 55º Congresso da Sociedade Brasileira de Medicina Tropical ◦ XXVI Congresso da Sociedade Brasileira de Parasitologia CHAGASLEISH 2019. Trabalho aparesentado no MEDTROP-Parasito 2019, realizado em Belo Horizonte no período de 28 a 31 de julho de 2019.
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spelling Oliveira, Helena D'Anunciação deBatista, Camila NunesLima, Maiara Nascimento deSilva, Adriano Yagho daRocco, Patricia Rieken MacedoFaria-Neto, Hugo Caire de CastroMaron-Gutierrez, Tatiana2023-08-24T17:34:08Z2023-08-24T17:34:08Z2019OLIVEIRA, Helena D'Anunciação de et al. Acetylsalicylic acid and combined therapy with dihydroartemisinin modulate lung injury on experimental malaria-associated ARDS. In: MEDTROP: PARASITO: CONGRESSO DA SOCIEDADE BRASILEIRA DE MEDICINA TROPICAL, 55., 2019; CONGRESSO DA SOCIEDADE BRASILEIRA DE PARASITOLOGIA CHAGASLEISH, 26., 2019. Belo Horizonte. Anais... Belo Horizonte: SBMT, 2019. p. 706-707.https://www.arca.fiocruz.br/handle/icict/6021155º Congresso da Sociedade Brasileira de Medicina Tropical ◦ XXVI Congresso da Sociedade Brasileira de Parasitologia CHAGASLEISH 2019. Trabalho aparesentado no MEDTROP-Parasito 2019, realizado em Belo Horizonte no período de 28 a 31 de julho de 2019.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.Prefeitura de Arraial do Cabo. Secretaria Municipal de Saúde. Arraial do Cabo, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.Severe malaria might have respiratory symptoms, which can progress to malaria-associated acute respiratory distress syndrome (MA-ARDS). Although mortality rate varies from 50 to 80% of cases, there is no specific treatment for MA-ARDS. In this context, the effects of acetylsalicylic acid (ASA), a non-steroidal anti-inflammatory widely used by population, including in endemic areas, on MA-ADRS remain unclear. Since combined artemisinin therapies are recommended by the World Health Organization, and dihydroartemisinin (DHA) have antimalarial and immunomodulatory proprieties, we hypothesized that ASA and combines therapy with DHA might prolong survival rate and modulate the inflammatory process in experimental MA-ARDS Aim: To evaluate the effects of acetylsalicylic acid (ASA) and combined therapy with dihydroarthemisinin (DHA) on experimental MA-ARDS. Methods: C57BL/6 mice were randomly divided in control (C) and infected (Pb) groups, intraperitoneally (ip) inoculated with uninfected erythrocytes or 104 Plasmodium berghei NK65 infected erythrocytes, respectively, and treated on day 8 orally with ASA (100mg/kg) or saline, and vehicle (DMSO) or DHA (3mg/kg), ip. Results: This is the first study that describes the functional impairment induced by PbNK65 on experimental MA-ARDS. For that, lung mechanics and pulmonary edema analysis were performed between days 6 to 10 post infection. PbNK65 led to increased lung static elastance (Est,L) on the 9th and 10th dpi (57±19cmH2O.ml-1; 71±4.8cmH2O.ml-1, respectively) increased resistive pressure (ΔP1,L) on the 10th dpi (0.9±0.3cmH2O.ml) and higher viscoelastic pressure (ΔP2,L) (0.9±0.1cmH2O.ml; 0.9±0.1cmH2O.ml and 1.1±0.3cmH2O.ml, respectively) from the 8th to 10th dpi, compared to C (Est,L= 35±3cmH2O.ml-1; ΔP1,L= 0.3±0.1cmH2O.ml; ΔP2,L=0.6±0.1cmH2O.ml) . PbNK65 infected mice showed a significant increase in lung edema on day 8 [5(5.1/4.7)] and 9 [4.8(5.1/4.7)] compared to control [4.4(4.6/4.2)]. Diffuse alveolar damage (DAD) score analysis have confirmed that both PbNK65 and Pb+DHA groups presented extravasation of fluid to alveolar space, alveolar septae thickening, edema and areas of microatelectasis compared to C. Lung hemorrhage was also observed in PbNK65 animals but not in Pb+DHA. Pb+DMSO presented thrombocytopenia (192±40 10³/ mm³) and leukocytosis (118±37 10³/mm³) on day 15. Seven days after DHA treatment, leukocytosis was reduced on Pb+DHA and Pb+DHA+ASA groups (11.5±7.8 10³/mm³ and 13±7.8 10³/mm³, respectively), but platelet count was maintained on Pb+DHA (376±151 10³/mm³) and ASA+DHA (312±139 10³/mm³). PbNK65 also led to increase on aspartate transaminase (AST) (619±112U/l) and decrease on serum albumin (2±0.1g/dL) and alkaline phosphatase (AP) (62±10U/l) levels compared to C group (AST= 108±47U/l; AP= 127±21U/l; Albumin= 2.5±0.1g/dL, respectively). Peripheral parasitemia on day 8 was directly correlated to increase on protein levels on bronchoalveolar lavage fluid (BALF) (r=0.72; p=0.0002). Pb+DMSO (5.8± 4.2mg/ml), Pb+ASA (4.4±3mg/ml) and Pb+DHA+ASA (3.7±2.5mg/ml) but not Pb+DHA (3.1±2.3mg/ml) showed higher protein levels on BAL compared to C (0.2± 0.09mg/ml). MCP-1 levels on BAL were higher in Pb+DMSO (300±146pg/ml) and Pb+DHA (221±189pg/ml) compared to C (4.9±2.8pg/ml) and decreased after and Pb+ASA (136±53pg/ml) or Pb+DHA+ASA (144±109pg/ml) treatment. Moreover, mononuclear cell count on lung tissue were higher on Pb+DMSO (41%) compared to C (30.6%) and decreased after Pb+DHA (35.1%), Pb+ASA (33%) and Pb+DHA+ASA (34%) treatment. On lung mechanics analysis, Pb+DMSO (72±10cmH2O.ml-1) and Pb+ASA (63±21cmH2O.ml-1) groups showed higher Est,L and DP1 (0.6±0.3cmH2O; 0.5±0.3cmH2O, respectively) than C (Est 42±6cmH2O.ml-1; DP1 0.4±0.1cmH2O); DP2 was higher on Pb+DMSO (1.1±0.3cmH2O) compared to C (0.7±0.1cmH2O). Pb+DHA (0.8±0.1cmH2O) and Pb+ASA (0.9±0.1cmH2O) groups presented reduced DP2 compared to Pb+DMSO. However, Pb+ASA (25%) presented similar survival rate to Pb+DMSO (27%). 78% of Pb+DHA+ASA and all Pb+DHA group survived until day 15. Conclusions: PbNK65 infection led to impairment on lung mechanics, lung edema and influx of macrophage and plasma proteins to the alveolar space. ASA and combined therapy with DHA reduced leukocytosis, MCP-1 levels on BAL and lung viscoelastic pressure, although did not decrease mortality associated to MA-ARDS.porSBMTAspirinaLesão PulmonarMaláriaTerapêuticaMEDTROP-ParasitoAnaisCongressoAspirinLung InjuryMalariaTherapeuticsCongressAspirinaLesão PulmonarMaláriaAcetylsalicylic acid and combined therapy with dihydroartemisinin modulate lung injury on experimental malaria-associated ARDSinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectinfo: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/60211/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALAcetylsalicylic acid and combined therapy with dihydroartemisinin.pdfAcetylsalicylic acid and combined therapy with 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dc.title.en_US.fl_str_mv Acetylsalicylic acid and combined therapy with dihydroartemisinin modulate lung injury on experimental malaria-associated ARDS
title Acetylsalicylic acid and combined therapy with dihydroartemisinin modulate lung injury on experimental malaria-associated ARDS
spellingShingle Acetylsalicylic acid and combined therapy with dihydroartemisinin modulate lung injury on experimental malaria-associated ARDS
Oliveira, Helena D'Anunciação de
Aspirina
Lesão Pulmonar
Malária
Terapêutica
MEDTROP-Parasito
Anais
Congresso
Aspirin
Lung Injury
Malaria
Therapeutics
Congress
Aspirina
Lesão Pulmonar
Malária
title_short Acetylsalicylic acid and combined therapy with dihydroartemisinin modulate lung injury on experimental malaria-associated ARDS
title_full Acetylsalicylic acid and combined therapy with dihydroartemisinin modulate lung injury on experimental malaria-associated ARDS
title_fullStr Acetylsalicylic acid and combined therapy with dihydroartemisinin modulate lung injury on experimental malaria-associated ARDS
title_full_unstemmed Acetylsalicylic acid and combined therapy with dihydroartemisinin modulate lung injury on experimental malaria-associated ARDS
title_sort Acetylsalicylic acid and combined therapy with dihydroartemisinin modulate lung injury on experimental malaria-associated ARDS
author Oliveira, Helena D'Anunciação de
author_facet Oliveira, Helena D'Anunciação de
Batista, Camila Nunes
Lima, Maiara Nascimento de
Silva, Adriano Yagho da
Rocco, Patricia Rieken Macedo
Faria-Neto, Hugo Caire de Castro
Maron-Gutierrez, Tatiana
author_role author
author2 Batista, Camila Nunes
Lima, Maiara Nascimento de
Silva, Adriano Yagho da
Rocco, Patricia Rieken Macedo
Faria-Neto, Hugo Caire de Castro
Maron-Gutierrez, Tatiana
author2_role author
author
author
author
author
author
dc.contributor.author.fl_str_mv Oliveira, Helena D'Anunciação de
Batista, Camila Nunes
Lima, Maiara Nascimento de
Silva, Adriano Yagho da
Rocco, Patricia Rieken Macedo
Faria-Neto, Hugo Caire de Castro
Maron-Gutierrez, Tatiana
dc.subject.other.en_US.fl_str_mv Aspirina
Lesão Pulmonar
Malária
Terapêutica
MEDTROP-Parasito
Anais
Congresso
topic Aspirina
Lesão Pulmonar
Malária
Terapêutica
MEDTROP-Parasito
Anais
Congresso
Aspirin
Lung Injury
Malaria
Therapeutics
Congress
Aspirina
Lesão Pulmonar
Malária
dc.subject.en.en_US.fl_str_mv Aspirin
Lung Injury
Malaria
Therapeutics
Congress
dc.subject.decs.en_US.fl_str_mv Aspirina
Lesão Pulmonar
Malária
description 55º Congresso da Sociedade Brasileira de Medicina Tropical ◦ XXVI Congresso da Sociedade Brasileira de Parasitologia CHAGASLEISH 2019. Trabalho aparesentado no MEDTROP-Parasito 2019, realizado em Belo Horizonte no período de 28 a 31 de julho de 2019.
publishDate 2019
dc.date.issued.fl_str_mv 2019
dc.date.accessioned.fl_str_mv 2023-08-24T17:34:08Z
dc.date.available.fl_str_mv 2023-08-24T17:34:08Z
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dc.identifier.citation.fl_str_mv OLIVEIRA, Helena D'Anunciação de et al. Acetylsalicylic acid and combined therapy with dihydroartemisinin modulate lung injury on experimental malaria-associated ARDS. In: MEDTROP: PARASITO: CONGRESSO DA SOCIEDADE BRASILEIRA DE MEDICINA TROPICAL, 55., 2019; CONGRESSO DA SOCIEDADE BRASILEIRA DE PARASITOLOGIA CHAGASLEISH, 26., 2019. Belo Horizonte. Anais... Belo Horizonte: SBMT, 2019. p. 706-707.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/60211
identifier_str_mv OLIVEIRA, Helena D'Anunciação de et al. Acetylsalicylic acid and combined therapy with dihydroartemisinin modulate lung injury on experimental malaria-associated ARDS. In: MEDTROP: PARASITO: CONGRESSO DA SOCIEDADE BRASILEIRA DE MEDICINA TROPICAL, 55., 2019; CONGRESSO DA SOCIEDADE BRASILEIRA DE PARASITOLOGIA CHAGASLEISH, 26., 2019. Belo Horizonte. Anais... Belo Horizonte: SBMT, 2019. p. 706-707.
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