Efeitos anti-hiperalgésico e anti-inflamatório da Kielmeyera rugosa Choisy (Clusiaceae) em roedores
Ano de defesa: | 2014 |
---|---|
Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | |
Tipo de documento: | Tese |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Sergipe
|
Programa de Pós-Graduação: |
Pós-Graduação em Ciências da Saúde
|
Departamento: |
Não Informado pela instituição
|
País: |
BR
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | https://ri.ufs.br/handle/riufs/3595 |
Resumo: | Plants of the genus Kielmeyera, family Clusiaceae are used by the population of the Northeast of the Brazil in traditional medicine to treat various diseases, such as pain and inflammation diseases. A recent study demonstrated antitumor activity for K. rugosa, however, other pharmacological activities have never been studied, for example antihyperalgesic and anti inflammatory activities. Thus, the aim of this study was to evaluate the antihyperalgesic and anti - inflammatory effects of the methanol extract from the stems of K. rugosa (MEKR) in rodents. Swiss mice (25-35 g ) were divided into groups and subjected to treatment with MEKR (., 100, 200 and 400 mg/kg, oral administration, p.o.) , vehicle (0.9% saline solution + 0.2% Tween 80) or standard drug (i.p.). The hypernociception was evaluated at times 0.5 , 1, 2 , and 3 hours after administration (i.pl.) of carrageenan (CG; 300 mg/paw), tumor necrosis factor-α (TNF-α, 100 pg/paw), Prostaglandin E2 (PGE2; 100ƞg/pata) or dopamine (DA, 30 μg/paw) using the digital analgesymeter (von Frey). In the evaluation of anti-inflammatory activity two protocols were used, the first induced by GC (300 mg/well) at 4 hours after pleurisy which the full and differential counts were made of leukocytes as well as the dosage levels of TNF-α and IL-1β pleural lavage. In another protocol conducted to investigate the anti-inflammatory activity corresponded to paw edema induced by GC (1 %/40μL), the paw volume was measured with the aid of plethysmometer at 0-6h after CG. The cytotoxicity of MEKR was evaluated by the MTT colorimetric method. To determine the possible involvement of areas of the Central Nervous System (CNS), the animals were treated and ninety minutes, were anesthetized, perfused, the brains extracted and cut into the cryostat. The brain sections were subjected to immunofluorescence protocol for Fos protein. The motor coordination of the animal was assessed by the Rota Rod test (7 rpm, 180 s). The experimental protocols were approved by the ethics committee of the UFS (CEPA/UFS: 102/11) The results were expressed as mean ± standard error of the mean. Differences between groups were analyzed using the ANOVA one way followed by Tukey s test. The acute pretreatment with MEKR significantly inhibited hyperalgesia induced by nociceptive agents, CG, TNF-α, PGE2 and DA (p < 0.001). The MEKR inhibited the leukocyte recruitment into the pleural cavity (p < 0.01). This was due to the inhibition of leukocyte migration inhibition of neutrophils. The levels of cytokines, TNF-α (p < 0.01) and IL-1β (p < 0.001) were also reduced when the animals were treated with MEKR. MEKR decreased edema formation induced by CG (p < 0.001). However, MEKR showed no cytotoxic effect or change in motor coordination animals. In the Fos protein immunofluorescence test, MEKR showed that the olfactory bulb (p < 0.01), piriform cortex (p < 0.01) and periaqueductal gray (p < 0.001) for the active significantly of the CNS. Therefore, we conclude that MEKR has antihyperalgesic activity probably by activating the central nervous system areas associated with pain modulation and by reduction the production of proinflammatory cytokines, without traces of cytotoxicity. |
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Melo, Mônica Santos dehttp://lattes.cnpq.br/4178844355922772Quintans Júnior, Lucindo Joséhttp://lattes.cnpq.br/53604090326874722017-09-26T12:07:18Z2017-09-26T12:07:18Z2014-03-28MELO, Mônica Santos de. Anti-hyperalgesic and antiinflammatory effects of Kielmeyera rugosa choisy (clusiaceae) in mice. 2014. 100 f. Tese (Doutorado em Ciências da Saúde) - Universidade Federal de Sergipe, Aracaju, 2014.https://ri.ufs.br/handle/riufs/3595Plants of the genus Kielmeyera, family Clusiaceae are used by the population of the Northeast of the Brazil in traditional medicine to treat various diseases, such as pain and inflammation diseases. A recent study demonstrated antitumor activity for K. rugosa, however, other pharmacological activities have never been studied, for example antihyperalgesic and anti inflammatory activities. Thus, the aim of this study was to evaluate the antihyperalgesic and anti - inflammatory effects of the methanol extract from the stems of K. rugosa (MEKR) in rodents. Swiss mice (25-35 g ) were divided into groups and subjected to treatment with MEKR (., 100, 200 and 400 mg/kg, oral administration, p.o.) , vehicle (0.9% saline solution + 0.2% Tween 80) or standard drug (i.p.). The hypernociception was evaluated at times 0.5 , 1, 2 , and 3 hours after administration (i.pl.) of carrageenan (CG; 300 mg/paw), tumor necrosis factor-α (TNF-α, 100 pg/paw), Prostaglandin E2 (PGE2; 100ƞg/pata) or dopamine (DA, 30 μg/paw) using the digital analgesymeter (von Frey). In the evaluation of anti-inflammatory activity two protocols were used, the first induced by GC (300 mg/well) at 4 hours after pleurisy which the full and differential counts were made of leukocytes as well as the dosage levels of TNF-α and IL-1β pleural lavage. In another protocol conducted to investigate the anti-inflammatory activity corresponded to paw edema induced by GC (1 %/40μL), the paw volume was measured with the aid of plethysmometer at 0-6h after CG. The cytotoxicity of MEKR was evaluated by the MTT colorimetric method. To determine the possible involvement of areas of the Central Nervous System (CNS), the animals were treated and ninety minutes, were anesthetized, perfused, the brains extracted and cut into the cryostat. The brain sections were subjected to immunofluorescence protocol for Fos protein. The motor coordination of the animal was assessed by the Rota Rod test (7 rpm, 180 s). The experimental protocols were approved by the ethics committee of the UFS (CEPA/UFS: 102/11) The results were expressed as mean ± standard error of the mean. Differences between groups were analyzed using the ANOVA one way followed by Tukey s test. The acute pretreatment with MEKR significantly inhibited hyperalgesia induced by nociceptive agents, CG, TNF-α, PGE2 and DA (p < 0.001). The MEKR inhibited the leukocyte recruitment into the pleural cavity (p < 0.01). This was due to the inhibition of leukocyte migration inhibition of neutrophils. The levels of cytokines, TNF-α (p < 0.01) and IL-1β (p < 0.001) were also reduced when the animals were treated with MEKR. MEKR decreased edema formation induced by CG (p < 0.001). However, MEKR showed no cytotoxic effect or change in motor coordination animals. In the Fos protein immunofluorescence test, MEKR showed that the olfactory bulb (p < 0.01), piriform cortex (p < 0.01) and periaqueductal gray (p < 0.001) for the active significantly of the CNS. Therefore, we conclude that MEKR has antihyperalgesic activity probably by activating the central nervous system areas associated with pain modulation and by reduction the production of proinflammatory cytokines, without traces of cytotoxicity.Diversas plantas do gênero Kielmeyera, família Clusiaceae são utilizadas pela população do Nordeste brasileiro na medicina tradicional para o tratamento de diversas doenças, incluindo distúrbios dolorosos e inflamatórios. Um estudo recente demonstrou atividade antitumoral para a K. rugosa, no entanto, outras atividades farmacológicas nunca foram estudadas para esta espécie vegetal, por exemplo seu possível perfil analgésico e anti-inflamatório. Dessa forma, o objetivo do trabalho foi avaliar o efeito antihiperalgésico e anti-inflamatório do extrato metanólico obtido do caule de K. rugosa (EMKR) em roedores. Foram utilizados camundongos Swiss machos (25-35 g), divididos em grupos e submetidos ao tratamento agudo com EMKR (100, 200 e 400 mg/kg; por via oral, v.o.), veículo (solução salina 0,9% + tween 80 0,2%; v.o.) ou droga padrão (i.p.). A hipernocicepção foi avaliada nos tempos 0,5, 1, 2 e 3 h após a administração (i.pl.) de carragenina (CG; 300 μg/pata), Fator de necrose tumoral-α (TNF-α; 100 pg/pata), Prostaglandina E2 (PGE2; 100ƞg/pata) ou Dopamina (DA; 30 μg/pata), e foram avaliados utilizando-se o analgesímetro digital (Von Frey). Na avaliação da atividade anti-inflamatória foram utilizados dois protocolos, o primeiro de pleurisia induzida por CG (300 μg/cavidade), no qual após 4 horas foram realizadas as contagens total e diferencial de leucócitos, bem como as dosagens dos níveis de TNF-α e IL-1β do lavado pleural. Em outro protocolo realizado para investigar à atividade anti-inflamatória correspondeu ao edema de pata induzida por CG (1%/40μL); o volume da pata foi medido com auxílio do pletismomêtro nos tempos 0-6h após a CG. A citotoxicidade do MEKR foi avaliada através do método colorimétrico do MTT. Para determinar o possível envolvimento de áreas do Sistema Nervoso Central (SNC), os animais foram tratados e, noventa minutos após, foram anestesiados, perfundidos, os cérebros extraídos e cortados em criostato. As secções cerebrais foram submetidas ao protocolo de imunofluorescência para proteína Fos. A coordenação motora do animal foi avaliada através do teste do Rota Rod (7 rpm, 180 s). Os protocolos experimentais foram aprovados pelo comitê de ética da UFS (CEPA/UFS: 102/11) Os resultados foram expressos como média ± erro padrão da média. As diferenças entre os grupos foram analisadas por meio do teste de variância ANOVA, uma via, seguido pelo teste de Tukey. O pré-tratamento com EMKR inibiu significativamente a hiperalgesia induzida pelos agentes álgicos, CG, TNF-α, PGE2 e DA (p < 0,001). O EMKR também foi capaz de inibir o recrutamento leucocitário para a cavidade pleural (p < 0,01). Esta inibição leucocitária ocorreu devido à inibição na migração dos neutrófilos. Os níveis das citocinas, TNF-α (p < 0,01) e IL-1β (p < 0,001) também foram reduzidos quando os animais foram tratados com EMKR. Quanto ao edema, o EMKR diminuiu a formação induzida pela CG (p < 0,001). No entanto, o MEKR não apresentou efeito citotóxico ou alteração da coordenação motora dos animais. No teste de imunofluorescência para proteína Fos, o tratamento com MEKR ativou significativamente o bulbo olfatório (p < 0,01), córtex piriforme (p < 0,01) e a substância cinzenta periaquedutal (p < 0,001), áreas do SNC. Os resultados sugerem que o MEKR possui atividade antihiperalgésica e anti-inflamatória provavelmente por ativação de áreas do sistema nervoso central relacionadas com a modulação da dor e por reduzir a produção de citocinas pró-inflamatórias, sem traços de citotoxicidade.application/pdfporUniversidade Federal de SergipePós-Graduação em Ciências da SaúdeUFSBRClusiaceaeKielemeyera rugosaDorInflamaçãoProteína FosSubstância cinzenta periaqueductalClusiaceaeKielmeyera rugosa ChoisyPainInflammationFos proteinPeriaqueductal grayCNPQ::CIENCIAS DA SAUDEEfeitos anti-hiperalgésico e anti-inflamatório da Kielmeyera rugosa Choisy (Clusiaceae) em roedoresAnti-hyperalgesic and antiinflammatory effects of Kielmeyera rugosa choisy (clusiaceae) in miceinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFSinstname:Universidade Federal de Sergipe (UFS)instacron:UFSTEXTMONICA_SANTOS_MELO.pdf.txtMONICA_SANTOS_MELO.pdf.txtExtracted texttext/plain156826https://ri.ufs.br/jspui/bitstream/riufs/3595/2/MONICA_SANTOS_MELO.pdf.txtbdb5f354577e8a607697904fc5ec8978MD52THUMBNAILMONICA_SANTOS_MELO.pdf.jpgMONICA_SANTOS_MELO.pdf.jpgGenerated Thumbnailimage/jpeg1319https://ri.ufs.br/jspui/bitstream/riufs/3595/3/MONICA_SANTOS_MELO.pdf.jpg3a50b9b1c1b16919b0f6e54c51b66903MD53ORIGINALMONICA_SANTOS_MELO.pdfapplication/pdf1633684https://ri.ufs.br/jspui/bitstream/riufs/3595/1/MONICA_SANTOS_MELO.pdf6fe05edb7f0c74177eabeb528e58d41eMD51riufs/35952017-11-28 16:36:53.649oai:ufs.br:riufs/3595Repositório InstitucionalPUBhttps://ri.ufs.br/oai/requestrepositorio@academico.ufs.bropendoar:2017-11-28T19:36:53Repositório Institucional da UFS - Universidade Federal de Sergipe (UFS)false |
dc.title.por.fl_str_mv |
Efeitos anti-hiperalgésico e anti-inflamatório da Kielmeyera rugosa Choisy (Clusiaceae) em roedores |
dc.title.alternative.eng.fl_str_mv |
Anti-hyperalgesic and antiinflammatory effects of Kielmeyera rugosa choisy (clusiaceae) in mice |
title |
Efeitos anti-hiperalgésico e anti-inflamatório da Kielmeyera rugosa Choisy (Clusiaceae) em roedores |
spellingShingle |
Efeitos anti-hiperalgésico e anti-inflamatório da Kielmeyera rugosa Choisy (Clusiaceae) em roedores Melo, Mônica Santos de Clusiaceae Kielemeyera rugosa Dor Inflamação Proteína Fos Substância cinzenta periaqueductal Clusiaceae Kielmeyera rugosa Choisy Pain Inflammation Fos protein Periaqueductal gray CNPQ::CIENCIAS DA SAUDE |
title_short |
Efeitos anti-hiperalgésico e anti-inflamatório da Kielmeyera rugosa Choisy (Clusiaceae) em roedores |
title_full |
Efeitos anti-hiperalgésico e anti-inflamatório da Kielmeyera rugosa Choisy (Clusiaceae) em roedores |
title_fullStr |
Efeitos anti-hiperalgésico e anti-inflamatório da Kielmeyera rugosa Choisy (Clusiaceae) em roedores |
title_full_unstemmed |
Efeitos anti-hiperalgésico e anti-inflamatório da Kielmeyera rugosa Choisy (Clusiaceae) em roedores |
title_sort |
Efeitos anti-hiperalgésico e anti-inflamatório da Kielmeyera rugosa Choisy (Clusiaceae) em roedores |
author |
Melo, Mônica Santos de |
author_facet |
Melo, Mônica Santos de |
author_role |
author |
dc.contributor.author.fl_str_mv |
Melo, Mônica Santos de |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/4178844355922772 |
dc.contributor.advisor1.fl_str_mv |
Quintans Júnior, Lucindo José |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/5360409032687472 |
contributor_str_mv |
Quintans Júnior, Lucindo José |
dc.subject.por.fl_str_mv |
Clusiaceae Kielemeyera rugosa Dor Inflamação Proteína Fos Substância cinzenta periaqueductal |
topic |
Clusiaceae Kielemeyera rugosa Dor Inflamação Proteína Fos Substância cinzenta periaqueductal Clusiaceae Kielmeyera rugosa Choisy Pain Inflammation Fos protein Periaqueductal gray CNPQ::CIENCIAS DA SAUDE |
dc.subject.eng.fl_str_mv |
Clusiaceae Kielmeyera rugosa Choisy Pain Inflammation Fos protein Periaqueductal gray |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS DA SAUDE |
description |
Plants of the genus Kielmeyera, family Clusiaceae are used by the population of the Northeast of the Brazil in traditional medicine to treat various diseases, such as pain and inflammation diseases. A recent study demonstrated antitumor activity for K. rugosa, however, other pharmacological activities have never been studied, for example antihyperalgesic and anti inflammatory activities. Thus, the aim of this study was to evaluate the antihyperalgesic and anti - inflammatory effects of the methanol extract from the stems of K. rugosa (MEKR) in rodents. Swiss mice (25-35 g ) were divided into groups and subjected to treatment with MEKR (., 100, 200 and 400 mg/kg, oral administration, p.o.) , vehicle (0.9% saline solution + 0.2% Tween 80) or standard drug (i.p.). The hypernociception was evaluated at times 0.5 , 1, 2 , and 3 hours after administration (i.pl.) of carrageenan (CG; 300 mg/paw), tumor necrosis factor-α (TNF-α, 100 pg/paw), Prostaglandin E2 (PGE2; 100ƞg/pata) or dopamine (DA, 30 μg/paw) using the digital analgesymeter (von Frey). In the evaluation of anti-inflammatory activity two protocols were used, the first induced by GC (300 mg/well) at 4 hours after pleurisy which the full and differential counts were made of leukocytes as well as the dosage levels of TNF-α and IL-1β pleural lavage. In another protocol conducted to investigate the anti-inflammatory activity corresponded to paw edema induced by GC (1 %/40μL), the paw volume was measured with the aid of plethysmometer at 0-6h after CG. The cytotoxicity of MEKR was evaluated by the MTT colorimetric method. To determine the possible involvement of areas of the Central Nervous System (CNS), the animals were treated and ninety minutes, were anesthetized, perfused, the brains extracted and cut into the cryostat. The brain sections were subjected to immunofluorescence protocol for Fos protein. The motor coordination of the animal was assessed by the Rota Rod test (7 rpm, 180 s). The experimental protocols were approved by the ethics committee of the UFS (CEPA/UFS: 102/11) The results were expressed as mean ± standard error of the mean. Differences between groups were analyzed using the ANOVA one way followed by Tukey s test. The acute pretreatment with MEKR significantly inhibited hyperalgesia induced by nociceptive agents, CG, TNF-α, PGE2 and DA (p < 0.001). The MEKR inhibited the leukocyte recruitment into the pleural cavity (p < 0.01). This was due to the inhibition of leukocyte migration inhibition of neutrophils. The levels of cytokines, TNF-α (p < 0.01) and IL-1β (p < 0.001) were also reduced when the animals were treated with MEKR. MEKR decreased edema formation induced by CG (p < 0.001). However, MEKR showed no cytotoxic effect or change in motor coordination animals. In the Fos protein immunofluorescence test, MEKR showed that the olfactory bulb (p < 0.01), piriform cortex (p < 0.01) and periaqueductal gray (p < 0.001) for the active significantly of the CNS. Therefore, we conclude that MEKR has antihyperalgesic activity probably by activating the central nervous system areas associated with pain modulation and by reduction the production of proinflammatory cytokines, without traces of cytotoxicity. |
publishDate |
2014 |
dc.date.issued.fl_str_mv |
2014-03-28 |
dc.date.accessioned.fl_str_mv |
2017-09-26T12:07:18Z |
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2017-09-26T12:07:18Z |
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info:eu-repo/semantics/doctoralThesis |
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MELO, Mônica Santos de. Anti-hyperalgesic and antiinflammatory effects of Kielmeyera rugosa choisy (clusiaceae) in mice. 2014. 100 f. Tese (Doutorado em Ciências da Saúde) - Universidade Federal de Sergipe, Aracaju, 2014. |
dc.identifier.uri.fl_str_mv |
https://ri.ufs.br/handle/riufs/3595 |
identifier_str_mv |
MELO, Mônica Santos de. Anti-hyperalgesic and antiinflammatory effects of Kielmeyera rugosa choisy (clusiaceae) in mice. 2014. 100 f. Tese (Doutorado em Ciências da Saúde) - Universidade Federal de Sergipe, Aracaju, 2014. |
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Universidade Federal de Sergipe |
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