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| DC Field | Value | Language |
|---|---|---|
| dc.contributor.author | Santana, Raissa Couto | - |
| dc.date.accessioned | 2025-07-11T16:20:19Z | - |
| dc.date.available | 2025-07-11T16:20:19Z | - |
| dc.date.issued | 2023-09-20 | - |
| dc.identifier.citation | SANTANA, Raíssa Couto. Análise da atividade leishmanicida do derivado sintético da piperina e do efeito imunomodulatório do composto sintético e de compostos naturais em linhagens de macrófagos murinos e canino. 2023. 103 f. Tese (Doutorado em Ciências Veterinárias) - Instituto de Veterinária, Universidade Federal do Rio de Janeiro, Seropédica, 2023. | pt_BR |
| dc.identifier.uri | https://rima.ufrrj.br/jspui/handle/20.500.14407/22345 | - |
| dc.description.abstract | Os macrófagos são células fagocíticas presentes em diversos órgãos envolvidos na homeostase e proteção dos tecidos. Os macrófagos são as células hospedeiras do parasito Leishamania sp. agente causador da leishmaniose que aflige 1 milhão de pessoas anualmente. Os medicamentos são tóxicos e extremamente caros. Produtos naturais apresentam ação farmacológica com fácil acesso e na maioria seguros, além de apresentarem estruturas químicas que permitem modificações para seu aperfeiçoamento. Nosso grupo demonstrou anteriormente que 2 produtos naturais, (-)-Guaiol e Piperina (AF1) apresentam atividade leishmanicida para espécies de Leishmania amazonensis. Nesse trabalho confirmamos essa ação dos compostos naturais e estudamos pela primeira vez a atividade antileishmania do derivado sintético de piperina N4-cyclohexyl-1,2,4- triazol-3-thione (AF2). Avaliamos também a ação imunomoduladora dos compostos em diferentes linhagens celulares de macrófagos murinos P388D1 e RAW 264.7 e canino DH82. Os compostos demonstraram uma atividade leishmanicida in vitro para promastigotas de L. amazonensis com IC50 de 56.24 μM, 9.36 μM e 8.73 μM para (-)- Guaiol, AF1 e AF2, respectivamente. As linhagens celulares apresentaram viabilidade acima de 70% após tratamentos com os compostos. AF2 na concentração de 50 μM diminuiu a atividade fagocítica de DH82 após desafio com formas promastigotas. Os tratamentos com os compostos levaram a modulação na produção de NO e ROS e alterou a expressão de moléculas MHC I/II, CD80 e CD86 nas diferentes linhagens. Por fim, resultados de qPCR demonstram que linhagem RAW 264.7 e DH82 aumentam a expressão de mRNA da citocina IL 10 após tratamento com (-)-Guaiol e AF1 enquanto que os compostos diminuem a expressão de IL 10, IL 12, TLR4 e TLR9 nessas células quando estimuladas com LPS. A linhagem celular P388D1 em repouso e tratadas com (- )-Guaiol e AF1 levaram a uma redução da expressão de TLR4. Os resultados sugerem que o efeito dos compostos pode ser diferente dependendo do tipo celular. | pt_BR |
| dc.description.sponsorship | Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES | pt_BR |
| dc.language | por | pt_BR |
| dc.publisher | Universidade Federal Rural do Rio de Janeiro | pt_BR |
| dc.subject | Atividade imunomoduladora | pt_BR |
| dc.subject | tratamentos | pt_BR |
| dc.subject | produtos naturais e sintéticos | pt_BR |
| dc.subject | Immunomodulatory activity | pt_BR |
| dc.subject | treatment | pt_BR |
| dc.subject | natural and synthetic products | pt_BR |
| dc.title | Análise da atividade leishmanicida do derivado sintético da piperina e do efeito imunomodulatório do composto sintético e de compostos naturais em linhagens de macrófagos murinos e canino | pt_BR |
| dc.title.alternative | Analysis of the leishmanicidal activity of the synthetic piperine derivative and the immunomodulatory effect of the synthetic compound and natural compounds in murine and canine macrophage lines | en |
| dc.type | Tese | pt_BR |
| dc.description.abstractOther | Macrophages are phagocytic cells situated in various organs involved in homeostasis and tissue protection. Macrophages are the host cells of the Leishamania sp. parasite causative agent of leishmaniasis that afflicts 1 million people annually. The treatments are toxic and extremely expensive. Natural products have pharmacological activity that is easy to access and mostly safe to use. In addition, having chemical structures that allow modifications for improvement. Our group previously demonstrated that 2 natural products, (-)-Guaiol and Piperine (AF1) have leishmanicidal activity against Leishmania amazonensis species. In this work, we confirmed this activity of natural compounds and studied for the first time the antileishmanial activity of the synthetic piperine derivative N4-cyclohexyl-1,2,4-triazol-3-thione (AF2). We also evaluated the immunomodulatory activity of the compounds in different macrophages cell lines of murine (P388D1 and RAW 264.7) and canine DH82. The compounds demonstrated in vitro leishmanicidal activity for L. amazonensis promastigotes with IC50 of 56.24 μM, 9.36 μM and 8.73 μM for (-)-Guaiol, AF1 and AF2, respectively. The cell lines showed viability above 70% after treatment with the compounds. AF2 at a concentration of 50 μM decreased the phagocytic activity of DH82 after challenge with promastigote forms. Treatment with the compounds modulate the production of NO and ROS and altered the expression of MHC I/II, CD80 and CD86 molecules in different lineages. Finally, qPCR results demonstrate that RAW 264.7 and DH82 strains increase the mRNA expression of the cytokine IL-10 after treatment with (-)-Guaiol and AF1, while the compounds decrease the expression of IL-10, IL-12, TLR4 and TLR9 in these cells when stimulated with LPS. Resting cell line P388D1 treated with (-)-Guaiol and AF1 led to a reduction in TLR4 expression. The results suggest that the effect of the compounds may be different depending on the cell type. | en |
| dc.contributor.advisor1 | Silva, Lucia Helena Pinto da | - |
| dc.contributor.advisor1ID | https://orcid.org/0000-0002-7085-8649 | pt_BR |
| dc.contributor.advisor1Lattes | http://lattes.cnpq.br/0013386072339397 | pt_BR |
| dc.contributor.advisor-co1 | Santos-Gomes, Gabriela | - |
| dc.contributor.advisor-co1Lattes | http://lattes.cnpq.br/1344635636229785 | pt_BR |
| dc.contributor.referee1 | Lima, Debora Decote Ricardo de | - |
| dc.contributor.referee1ID | https://orcid.org/0000-0001-8761-7641 | pt_BR |
| dc.contributor.referee1Lattes | http://lattes.cnpq.br/3572066508469025 | pt_BR |
| dc.contributor.referee2 | Silva, Lucia Helena Pinto da | - |
| dc.contributor.referee2ID | https://orcid.org/0000-0002-7085-8649 | pt_BR |
| dc.contributor.referee2Lattes | http://lattes.cnpq.br/0013386072339397 | pt_BR |
| dc.contributor.referee3 | Amaral, Veronica Figueiredo do | - |
| dc.contributor.referee3Lattes | http://lattes.cnpq.br/2432524610182899 | pt_BR |
| dc.contributor.referee4 | Freire-de-Lima, Leonardo | - |
| dc.contributor.referee4ID | https://orcid.org/0000-0003-3013-3173 | pt_BR |
| dc.contributor.referee4Lattes | http://lattes.cnpq.br/1632438969296293 | pt_BR |
| dc.contributor.referee5 | Almeida, Renato Porrozzi de | - |
| dc.contributor.referee5Lattes | http://lattes.cnpq.br/7510128797755635 | pt_BR |
| dc.creator.ID | https://orcid.org/0000-0001-5883-3783 | pt_BR |
| dc.creator.Lattes | http://lattes.cnpq.br/2711105842691744 | pt_BR |
| dc.publisher.country | Brasil | pt_BR |
| dc.publisher.department | Instituto de Veterinária | pt_BR |
| dc.publisher.initials | UFRRJ | pt_BR |
| dc.publisher.program | Programa de Pós-Graduação em Ciências Veterinárias | pt_BR |
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| dc.subject.cnpq | Parasitologia | pt_BR |
| Appears in Collections: | Doutorado em Ciências Veterinárias | |
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