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DC Field | Value | Language |
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dc.contributor | Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP | - |
dc.contributor.author | CUNHA-JUNIOR, Edezio Ferreira | - |
dc.contributor.author | ANDRADE-NETO, Valter Viana | - |
dc.contributor.author | LIMA, Marta Lopes | - |
dc.contributor.author | COSTA-SILVA, Thais Alves da | - |
dc.contributor.author | GALISTEO JUNIOR, Andres J. | - |
dc.contributor.author | ABENGOZAR, Maria A. | - |
dc.contributor.author | BARBAS, Coral | - |
dc.contributor.author | RIVAS, Luis | - |
dc.contributor.author | ALMEIDA-AMARAL, Elmo Eduardo | - |
dc.contributor.author | TEMPONE, Andre Gustavo | - |
dc.contributor.author | TORRES-SANTOS, Eduardo Caio | - |
dc.date.accessioned | 2017-04-07T15:22:09Z | - |
dc.date.available | 2017-04-07T15:22:09Z | - |
dc.date.issued | 2017 | - |
dc.identifier.citation | PLOS NEGLECTED TROPICAL DISEASES, v.11, n.1, article ID e0005281, 11p, 2017 | - |
dc.identifier.issn | 1935-2735 | - |
dc.identifier.uri | https://observatorio.fm.usp.br/handle/OPI/19149 | - |
dc.description.abstract | Background The leishmanicidal action of tricyclic antidepressants has been studied and evidences have pointed that their action is linked to inhibition of trypanothione reductase, a key enzyme in the redox metabolism of pathogenic trypanosomes. Cyclobenzaprine (CBP) is a tricyclic structurally related to the antidepressant amitriptyline, differing only by the presence of a double bond in the central ring. This paper describes the effect of CBP in experimental visceral leishmaniasis, its inhibitory effect in trypanothione reductase and the potential immunomodulatory activity. Methodology/Principal Findings In vitro antileishmanial activity was determined in promastigotes and in L. infantum-infected macrophages. For in vivo studies, L. infantum-infected BALB/c mice were treated with CBP by oral gavage for five days and the parasite load was estimated. Trypanothione reductase activity was assessed in the soluble fraction of promastigotes of L. infantum. For evaluation of cytokines, L. infantum-infected macrophages were co-cultured with BALB/c splenocytes and treated with CBP for 48 h. The supernatant was analyzed for IL-6, IL-10, MCP-1, IFN-gamma and TNF-alpha. CBP demonstrated an IC50 of 14.5 +/- 1.1 mu M and an IC90 of 74.5 +/- 1.2 mu M in promastigotes and an IC50 of 12.6 +/- 1.05 mu M and an IC90 of 28.7 +/- 1.3 mu M in intracellular amastigotes. CBP also reduced the parasite load in L. infantum-infected mice by 40.4 +/- 10.3% and 66.7 +/- 10.5% in spleen at 24.64 and 49.28 mg/kg, respectively and by 85.6 +/- 5.0 and 89.3 +/- 4.8% in liver at 24.64 and 49.28mg/kg, after a short-term treatment. CBP inhibited the trypanothione reductase activity with a Ki of 86 +/- 7.7 mu M and increased the ROS production in promastigotes. CBP inhibited in 53% the production of IL-6 in infected macrophages coculture. Conclusion/Significance To the best of our knowledge, this study is the first report of the in vivo antileishmanial activity of the FDA-approved drug CBP. Modulation of immune response and induction of oxidative stress in parasite seem to contribute to this efficacy. | - |
dc.description.sponsorship | Programa Estrategico de Apoio a Pesquisa em Saude, FIOCRUZ/Conselho Nacional de Desenvolvimento Cientifico e Tecnologico [PAPES/CNPq 407680/2012-8, 407590/2012-9] | - |
dc.description.sponsorship | Fundacao de Apoio a Pesquisa do Estado do Rio de Janeiro [E-26/010.001828/2016] | - |
dc.description.sponsorship | Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq/Universal grant) [470627/2013-1] | - |
dc.description.sponsorship | Sao Paulo Research Foundation [FAPESP 2015/23403-9] | - |
dc.description.sponsorship | Programa Estatal de Investigacion, Desarrollo e Innovacion Orientada a los Retos de la Sociedad FEDER [SAF2015-65740-R] | - |
dc.description.sponsorship | Subdireccion General de Redes y Centros de Investigacion Cooperativa-FEDER [RD12/0018/0007] | - |
dc.language.iso | eng | - |
dc.publisher | PUBLIC LIBRARY SCIENCE | - |
dc.relation.ispartof | Plos Neglected Tropical Diseases | - |
dc.rights | openAccess | - |
dc.subject.other | trypanothione reductase | - |
dc.subject.other | visceral leishmaniasis | - |
dc.subject.other | kala-azar | - |
dc.subject.other | macrophages | - |
dc.subject.other | inhibitors | - |
dc.subject.other | donovani | - |
dc.subject.other | drugs | - |
dc.title | Cyclobenzaprine Raises ROS Levels in Leishmania infantum and Reduces Parasite Burden in Infected Mice | - |
dc.type | article | - |
dc.rights.holder | Copyright PUBLIC LIBRARY SCIENCE | - |
dc.identifier.doi | 10.1371/journal.pntd.0005281 | - |
dc.identifier.pmid | 28045892 | - |
dc.subject.wos | Infectious Diseases | - |
dc.subject.wos | Parasitology | - |
dc.subject.wos | Tropical Medicine | - |
dc.type.category | original article | - |
dc.type.version | publishedVersion | - |
hcfmusp.author.external | CUNHA-JUNIOR, Edezio Ferreira:Fiocruz MS, Inst Oswaldo Cruz, Lab Bioquim Tripanosomatideos, Rio De Janeiro, Brazil | - |
hcfmusp.author.external | ANDRADE-NETO, Valter Viana:Fiocruz MS, Inst Oswaldo Cruz, Lab Bioquim Tripanosomatideos, Rio De Janeiro, Brazil | - |
hcfmusp.author.external | COSTA-SILVA, Thais Alves da:Adolfo Lutz Inst, Ctr Parasitol & Micol, Sao Paulo, SP, Brazil | - |
hcfmusp.author.external | ABENGOZAR, Maria A.:CSIC, CEU, Unidad Asociada Interacc Metab & Bioanal, Ctr Invest Biol, Madrid, Spain | - |
hcfmusp.author.external | BARBAS, Coral:Univ CEU San Pablo, Fac Pharm, Ctr Metabol & Bioanal CEMBIO, Madrid, Spain | - |
hcfmusp.author.external | RIVAS, Luis:CSIC, CEU, Unidad Asociada Interacc Metab & Bioanal, Ctr Invest Biol, Madrid, Spain | - |
hcfmusp.author.external | ALMEIDA-AMARAL, Elmo Eduardo:Fiocruz MS, Inst Oswaldo Cruz, Lab Bioquim Tripanosomatideos, Rio De Janeiro, Brazil | - |
hcfmusp.author.external | TEMPONE, Andre Gustavo:Adolfo Lutz Inst, Ctr Parasitol & Micol, Sao Paulo, SP, Brazil | - |
hcfmusp.author.external | TORRES-SANTOS, Eduardo Caio:Fiocruz MS, Inst Oswaldo Cruz, Lab Bioquim Tripanosomatideos, Rio De Janeiro, Brazil | - |
hcfmusp.description.articlenumber | e0005281 | - |
hcfmusp.description.issue | 1 | - |
hcfmusp.description.volume | 11 | - |
hcfmusp.origem | WOS | - |
hcfmusp.origem.id | 2-s2.0-85012928631 | - |
hcfmusp.origem.id | WOS:000394152000052 | - |
hcfmusp.publisher.city | SAN FRANCISCO | - |
hcfmusp.publisher.country | USA | - |
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dc.description.index | MEDLINE | - |
hcfmusp.citation.scopus | 20 | - |
hcfmusp.scopus.lastupdate | 2024-04-12 | - |
Appears in Collections: | Artigos e Materiais de Revistas Científicas - IMT Artigos e Materiais de Revistas Científicas - LIM/49 |
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art_CUNHA-JUNIOR_Cyclobenzaprine_Raises_ROS_Levels_in_Leishmania_infantum_and_2017.PDF | publishedVersion (English) | 1.48 MB | Adobe PDF | View/Open |
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