Effect of phospholipase A2 inhibitors during infection caused by Leishmania (Leishmania) amazonensis
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1186/s40409-018-0156-9 http://hdl.handle.net/11449/176753 |
Resumo: | Background: Lipid metabolites play an important role in parasite differentiation and virulence. Studies have revealed that Leishmania sp. uses prostaglandins to evade innate barriers, thus enabling the parasites to survive inside immune cells. Despite the role of the enzyme Phospholipase A2 (PLA2) in prostaglandins production, few studies have investigated the role of parasite PLA2 during the interaction between L. (L.) amazonensis and the host (in vitro and in vivo) immune cells. Methods: In the present work, the leishmanicidal effect of PLA2 inhibitors, methyl arachidonyl fluorophosphonate (MAFP), bromoenol lactone (BEL) and aristolochic acid (AA) were investigated in vitro (promastigote and intracellular amastigote forms of L. (L.) amazonensis) and during in vivo infection using BALB/c mice. Results: The aforementioned inhibitors were deleterious to promastigote and amastigote forms of the L. (L.) amazonensis and were non-toxic to peritoneal macrophages from BALB/c mice. L. (L.) amazonensis-infected BALB/c mice treated with the inhibitor BEL presented decreased lesion size and skin parasitism; however, BEL treatment induced hepatotoxicity in BALB/c mice. Conclusions: Results presented herein suggested that PLA2 inhibitors altered L. (L.) amazonensis viability. In spite of liver toxicity, treatment with BEL was the most selective compound in vitro, as well in vivo, resulting in lower skin parasitism in the infected mice. These findings corroborate the role of PLA2 in parasite virulence and maintenance in vertebrate hosts, and suggest that molecules structurally related to BEL should be considered when planning compounds against Leishmania sp. |
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Effect of phospholipase A2 inhibitors during infection caused by Leishmania (Leishmania) amazonensisBALB/c miceLeishmania (Leishmania) amazonensisMacrophagesPhospholipase A2Phospholipase A2 inhibitorsBackground: Lipid metabolites play an important role in parasite differentiation and virulence. Studies have revealed that Leishmania sp. uses prostaglandins to evade innate barriers, thus enabling the parasites to survive inside immune cells. Despite the role of the enzyme Phospholipase A2 (PLA2) in prostaglandins production, few studies have investigated the role of parasite PLA2 during the interaction between L. (L.) amazonensis and the host (in vitro and in vivo) immune cells. Methods: In the present work, the leishmanicidal effect of PLA2 inhibitors, methyl arachidonyl fluorophosphonate (MAFP), bromoenol lactone (BEL) and aristolochic acid (AA) were investigated in vitro (promastigote and intracellular amastigote forms of L. (L.) amazonensis) and during in vivo infection using BALB/c mice. Results: The aforementioned inhibitors were deleterious to promastigote and amastigote forms of the L. (L.) amazonensis and were non-toxic to peritoneal macrophages from BALB/c mice. L. (L.) amazonensis-infected BALB/c mice treated with the inhibitor BEL presented decreased lesion size and skin parasitism; however, BEL treatment induced hepatotoxicity in BALB/c mice. Conclusions: Results presented herein suggested that PLA2 inhibitors altered L. (L.) amazonensis viability. In spite of liver toxicity, treatment with BEL was the most selective compound in vitro, as well in vivo, resulting in lower skin parasitism in the infected mice. These findings corroborate the role of PLA2 in parasite virulence and maintenance in vertebrate hosts, and suggest that molecules structurally related to BEL should be considered when planning compounds against Leishmania sp.University of São Paulo (USP) Laboratory of Pathology of Infectious Diseases (LIM-50) Medical School, Av. Dr. Arnaldo, 455Case Western Reserve University Pathology Department, 2103 Cornell RdSão Paulo State University (UNESP) Institute of Biosciences São Vicente, Praça Infante Dom Henrique, s/nCamilo Castelo Branco University (Unicastelo) School of Dentistry, Rua Carolina Fonseca, 584São Paulo State University (UNESP) Institute of Biosciences São Vicente, Praça Infante Dom Henrique, s/nUniversidade de São Paulo (USP)Pathology DepartmentUniversidade Estadual Paulista (Unesp)School of DentistryBordon, Maria L.A.C. [UNESP]Laurenti, Márcia D.Ribeiro, Susan PereiraToyama, Marcos H. [UNESP]Toyama, Daniela de O.Passero, Luiz Felipe D. [UNESP]2018-12-11T17:22:21Z2018-12-11T17:22:21Z2018-08-27info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://dx.doi.org/10.1186/s40409-018-0156-9Journal of Venomous Animals and Toxins Including Tropical Diseases, v. 24, n. 1, 2018.1678-91991678-9180http://hdl.handle.net/11449/17675310.1186/s40409-018-0156-9S1678-919920180001003122-s2.0-85052294503S1678-91992018000100312.pdfScopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengJournal of Venomous Animals and Toxins Including Tropical Diseases0,573info:eu-repo/semantics/openAccess2024-01-23T07:06:53Zoai:repositorio.unesp.br:11449/176753Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T23:45:11.924527Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Effect of phospholipase A2 inhibitors during infection caused by Leishmania (Leishmania) amazonensis |
title |
Effect of phospholipase A2 inhibitors during infection caused by Leishmania (Leishmania) amazonensis |
spellingShingle |
Effect of phospholipase A2 inhibitors during infection caused by Leishmania (Leishmania) amazonensis Bordon, Maria L.A.C. [UNESP] BALB/c mice Leishmania (Leishmania) amazonensis Macrophages Phospholipase A2 Phospholipase A2 inhibitors |
title_short |
Effect of phospholipase A2 inhibitors during infection caused by Leishmania (Leishmania) amazonensis |
title_full |
Effect of phospholipase A2 inhibitors during infection caused by Leishmania (Leishmania) amazonensis |
title_fullStr |
Effect of phospholipase A2 inhibitors during infection caused by Leishmania (Leishmania) amazonensis |
title_full_unstemmed |
Effect of phospholipase A2 inhibitors during infection caused by Leishmania (Leishmania) amazonensis |
title_sort |
Effect of phospholipase A2 inhibitors during infection caused by Leishmania (Leishmania) amazonensis |
author |
Bordon, Maria L.A.C. [UNESP] |
author_facet |
Bordon, Maria L.A.C. [UNESP] Laurenti, Márcia D. Ribeiro, Susan Pereira Toyama, Marcos H. [UNESP] Toyama, Daniela de O. Passero, Luiz Felipe D. [UNESP] |
author_role |
author |
author2 |
Laurenti, Márcia D. Ribeiro, Susan Pereira Toyama, Marcos H. [UNESP] Toyama, Daniela de O. Passero, Luiz Felipe D. [UNESP] |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Universidade de São Paulo (USP) Pathology Department Universidade Estadual Paulista (Unesp) School of Dentistry |
dc.contributor.author.fl_str_mv |
Bordon, Maria L.A.C. [UNESP] Laurenti, Márcia D. Ribeiro, Susan Pereira Toyama, Marcos H. [UNESP] Toyama, Daniela de O. Passero, Luiz Felipe D. [UNESP] |
dc.subject.por.fl_str_mv |
BALB/c mice Leishmania (Leishmania) amazonensis Macrophages Phospholipase A2 Phospholipase A2 inhibitors |
topic |
BALB/c mice Leishmania (Leishmania) amazonensis Macrophages Phospholipase A2 Phospholipase A2 inhibitors |
description |
Background: Lipid metabolites play an important role in parasite differentiation and virulence. Studies have revealed that Leishmania sp. uses prostaglandins to evade innate barriers, thus enabling the parasites to survive inside immune cells. Despite the role of the enzyme Phospholipase A2 (PLA2) in prostaglandins production, few studies have investigated the role of parasite PLA2 during the interaction between L. (L.) amazonensis and the host (in vitro and in vivo) immune cells. Methods: In the present work, the leishmanicidal effect of PLA2 inhibitors, methyl arachidonyl fluorophosphonate (MAFP), bromoenol lactone (BEL) and aristolochic acid (AA) were investigated in vitro (promastigote and intracellular amastigote forms of L. (L.) amazonensis) and during in vivo infection using BALB/c mice. Results: The aforementioned inhibitors were deleterious to promastigote and amastigote forms of the L. (L.) amazonensis and were non-toxic to peritoneal macrophages from BALB/c mice. L. (L.) amazonensis-infected BALB/c mice treated with the inhibitor BEL presented decreased lesion size and skin parasitism; however, BEL treatment induced hepatotoxicity in BALB/c mice. Conclusions: Results presented herein suggested that PLA2 inhibitors altered L. (L.) amazonensis viability. In spite of liver toxicity, treatment with BEL was the most selective compound in vitro, as well in vivo, resulting in lower skin parasitism in the infected mice. These findings corroborate the role of PLA2 in parasite virulence and maintenance in vertebrate hosts, and suggest that molecules structurally related to BEL should be considered when planning compounds against Leishmania sp. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-12-11T17:22:21Z 2018-12-11T17:22:21Z 2018-08-27 |
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.uri.fl_str_mv |
http://dx.doi.org/10.1186/s40409-018-0156-9 Journal of Venomous Animals and Toxins Including Tropical Diseases, v. 24, n. 1, 2018. 1678-9199 1678-9180 http://hdl.handle.net/11449/176753 10.1186/s40409-018-0156-9 S1678-91992018000100312 2-s2.0-85052294503 S1678-91992018000100312.pdf |
url |
http://dx.doi.org/10.1186/s40409-018-0156-9 http://hdl.handle.net/11449/176753 |
identifier_str_mv |
Journal of Venomous Animals and Toxins Including Tropical Diseases, v. 24, n. 1, 2018. 1678-9199 1678-9180 10.1186/s40409-018-0156-9 S1678-91992018000100312 2-s2.0-85052294503 S1678-91992018000100312.pdf |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Journal of Venomous Animals and Toxins Including Tropical Diseases 0,573 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
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1808129549213368320 |