Efeito do flavonoide galangina sobre a susceptibilidade às convulsões induzidas por pentilenotetrazol na presença de prostaglandina E2
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional Manancial UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/21515 |
Resumo: | Epilepsy is one of the most common chronic neurological diseases, characterized by recurrent epileptic seizures, where one-third of patients are refractory to existing treatments. Evidences have revealed association between neuroinflammation and increased susceptibility to seizures since there is a pronounced increase in the expression of key inflammatory mediators, such as prostaglandin E2 (PGE2) during seizures. The PGE2 has been demonstrated to stimulate the release of glutamate and to inhibit Na+ K+ -ATPase enzyme, which in fact may increase neuronal excitability, contributing to seizure. Knowing the important role of inflammation during seizures and existence of refractory to anticonvulsant treatment, the purpose initial of the present study was to investigate whether PGE2 increases to susceptibility to seizures induced by pentylenetetrazol (PTZ). Subsequently, we evaluate whether a compound isolated from the Piper aleyreanum plant, named Galangin, proved to be anti- inflammatory and protective in a nociception model induced by glutamate and PGE2, could have anticonvulsive activity in this study. For this, in the experiment 1, the mice were injected with PGE2 (100ng/2μl; intracerebroventricular (i.c.v.) and fifteen minutes later were injected with a subefective PTZ dose (35mg/kg, intraperitoneal (i.p) for evaluation of susceptibility to seizures. In the experiment 2, the mice were injected with Galangin (30mg/kg; i.p.) fifteen minutes before PGE2 injection, fifteen minutes later were injected with PTZ, in the same doses. Our results showed that the group treated com PGE2 increased the susceptibility to PTZ, causing myoclonic and generalized seizures, increasing the seizures duration and electroencephalographic wave amplitude. Furthermore, statistical analyzes showed that the treatment with PGE2 or PGE2 and PTZ combined increased IBA-1 (microglial marker), GFAP (astrocytic marker), 4-HNE (lipid peroxidation marker), VCAM-1 (vascular cell adhesion molecule 1) and p-PKAIIα (phosphorylated cAMP-dependent protein kinase) immunocontents. However, nor PTZ or PGE2 treatment changed the immunocontent of receptors of PGE2 (EP1, EP2 and EP3). Indeed, pre-treatment with Galangin prevented the convulsive behavior and decreased electroencephalographic wave amplitude as well as prevented reactive species production, microglial and astrocytic activation, decreased VCAM-1 immunocontent and phosphorylation state of PKAIIα induced by PGE2/PTZ. Therefore, this study suggests that the compound Galangin presented anticonvulsive and anti-inflammatory activities against the behavioral and neurochemical changes induced by administration of PGE2 and PTZ. However, further studies are needed to investigate the clinical implications of these findings and their underlying mechanisms. |
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2021-07-19T17:24:22Z2021-07-19T17:24:22Z2018-03-24http://repositorio.ufsm.br/handle/1/21515Epilepsy is one of the most common chronic neurological diseases, characterized by recurrent epileptic seizures, where one-third of patients are refractory to existing treatments. Evidences have revealed association between neuroinflammation and increased susceptibility to seizures since there is a pronounced increase in the expression of key inflammatory mediators, such as prostaglandin E2 (PGE2) during seizures. The PGE2 has been demonstrated to stimulate the release of glutamate and to inhibit Na+ K+ -ATPase enzyme, which in fact may increase neuronal excitability, contributing to seizure. Knowing the important role of inflammation during seizures and existence of refractory to anticonvulsant treatment, the purpose initial of the present study was to investigate whether PGE2 increases to susceptibility to seizures induced by pentylenetetrazol (PTZ). Subsequently, we evaluate whether a compound isolated from the Piper aleyreanum plant, named Galangin, proved to be anti- inflammatory and protective in a nociception model induced by glutamate and PGE2, could have anticonvulsive activity in this study. For this, in the experiment 1, the mice were injected with PGE2 (100ng/2μl; intracerebroventricular (i.c.v.) and fifteen minutes later were injected with a subefective PTZ dose (35mg/kg, intraperitoneal (i.p) for evaluation of susceptibility to seizures. In the experiment 2, the mice were injected with Galangin (30mg/kg; i.p.) fifteen minutes before PGE2 injection, fifteen minutes later were injected with PTZ, in the same doses. Our results showed that the group treated com PGE2 increased the susceptibility to PTZ, causing myoclonic and generalized seizures, increasing the seizures duration and electroencephalographic wave amplitude. Furthermore, statistical analyzes showed that the treatment with PGE2 or PGE2 and PTZ combined increased IBA-1 (microglial marker), GFAP (astrocytic marker), 4-HNE (lipid peroxidation marker), VCAM-1 (vascular cell adhesion molecule 1) and p-PKAIIα (phosphorylated cAMP-dependent protein kinase) immunocontents. However, nor PTZ or PGE2 treatment changed the immunocontent of receptors of PGE2 (EP1, EP2 and EP3). Indeed, pre-treatment with Galangin prevented the convulsive behavior and decreased electroencephalographic wave amplitude as well as prevented reactive species production, microglial and astrocytic activation, decreased VCAM-1 immunocontent and phosphorylation state of PKAIIα induced by PGE2/PTZ. Therefore, this study suggests that the compound Galangin presented anticonvulsive and anti-inflammatory activities against the behavioral and neurochemical changes induced by administration of PGE2 and PTZ. However, further studies are needed to investigate the clinical implications of these findings and their underlying mechanisms.A epilepsia é uma das doenças neurológicas crônicas mais comuns, caracterizadas por crises epilépticas recorrentes, onde um terço dos pacientes são refratários aos tratamentos existentes. Evidências tem revelado estreita associação entre neuroinflamação e o aumento da suscetibilidade às crises epilépticas, uma vez que existe pronunciada expressão de mediadores inflamatórios, como a prostaglandina E2 (PGE2) durante as crises. Como demonstrado, a PGE2 é capaz de estimular a liberação de glutamato bem como inibir a enzima Na + K + -ATPase, o que de fato pode aumentar a excitabilidade neuronal, contribuindo para as crises epilépticas. Sabendo do papel importante da inflamação durante as crises e a existência da refratariedade ao tratamento anticonvulsivante, o objetivo inicial do presente estudo foi investigar se PGE2 aumenta a susceptibilidade a convulsões induzidas por pentilenotetrazol (PTZ). Posteriormente, avaliamos se o composto isolado da planta Piper aleyreanum, nomeado Galangina, que demonstrou efeito anti-inflamatório e protetor em modelo de nocicepção induzido por glutamato e PGE2, poderia apresentar atividade anticonvulsivante neste estudo. Para isso, no experimento 1, os camundongos foram injetados com PGE2 (100ng/2 μl; i.c.v) e quinze minutos depois foram injetados com uma dose subefetiva de PTZ (35mg/kg, i.p.) para avaliação da susceptibilidade a convulsões. No experimento 2, os camundongos foram injetados com Galangina (30mg/kg; i.p.) quinze minutos antes da injeção de PGE2, e quinze minutos após injeção de PGE2, os camundongos foram injetados com PTZ, nas mesmas doses. Nossos resultados mostraram que o grupo tratado com PGE2 aumentou a susceptibilidade ao PTZ, causando crises mioclônicas e generalizadas, aumentando a duração das crises bem como a amplitude de ondas eletroencefalográficas. Além disso, análise estatística mostrou que o tratamento com PGE2 ou PGE2 e PTZ em combinação aumentou o imunoconteúdo de IBA-1 (marcador microglial), GFAP (marcador astrocítico), 4-HNE (marcador de peroxidação lipídica), VCAM-1 (molécula de adesão de celular vascular 1) e da enzima p-PKAIIa (proteína cinase dependente de AMPc- fosforilada). No entanto, nem o tratamento com PGE2 ou com PTZ alterou o imunoconteúdo dos receptores de PGE2 (EP1, EP2 e EP3). De fato, o pré-tratamento com Galangina preveniu o comportamento convulsivo e diminuiu a amplitude de ondas eletroencefalográficas, bem como impediu o aumento da produção de espécies reativas, a ativação microglial e astrocítica, diminuiu o imunoconteúdo da VCAM-1 e o estado de fosforilação da enzima PKAIIα induzidos por PGE2/PTZ. Portanto, este estudo sugere que o composto Galangina apresentou atividade anticonvulsiva e anti-inflamatória contra as alterações comportamentais e neuroquímicas induzidas pela administração de PGE2 e PTZ. No entanto, estudos adicionais são necessários para investigar as implicações clínicas desses achados e seus mecanismos subjacentes.porUniversidade Federal de Santa MariaCentro de Ciências Naturais e ExatasPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaUFSMBrasilBioquímicaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessNeuroinflamaçãoProstaglandina E2SusceptibilidadeCrises epilépticasGalanginaCórtex cerebralNeuroinflammationProstaglandin E2SusceptibilitySeizuresGalanginCerebral cortexCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAEfeito do flavonoide galangina sobre a susceptibilidade às convulsões induzidas por pentilenotetrazol na presença de prostaglandina E2Effect of flavonoid galangin on susceptibility to seizures pentylenetetrazole- induced in presence prostaglandin E2info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisFighera, Michele Rechiahttp://lattes.cnpq.br/8583392747509231Oliveira, Clarissa Vasconcelos deSouza, Mauren Assis dehttp://lattes.cnpq.br/8634796247382371Zorzi, Viviane Nogueira de2008000000026006006008306e5eb-747a-45a0-a023-955603a45dcd66629e44-76c2-4382-9069-8ad4b507f384614bd64f-c3f1-41d4-a1db-199e671f673b0fe9a980-55b1-4230-9b54-c7084a53cf8areponame:Repositório Institucional Manancial UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMLICENSElicense.txtlicense.txttext/plain; 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dc.title.por.fl_str_mv |
Efeito do flavonoide galangina sobre a susceptibilidade às convulsões induzidas por pentilenotetrazol na presença de prostaglandina E2 |
dc.title.alternative.eng.fl_str_mv |
Effect of flavonoid galangin on susceptibility to seizures pentylenetetrazole- induced in presence prostaglandin E2 |
title |
Efeito do flavonoide galangina sobre a susceptibilidade às convulsões induzidas por pentilenotetrazol na presença de prostaglandina E2 |
spellingShingle |
Efeito do flavonoide galangina sobre a susceptibilidade às convulsões induzidas por pentilenotetrazol na presença de prostaglandina E2 Zorzi, Viviane Nogueira de Neuroinflamação Prostaglandina E2 Susceptibilidade Crises epilépticas Galangina Córtex cerebral Neuroinflammation Prostaglandin E2 Susceptibility Seizures Galangin Cerebral cortex CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Efeito do flavonoide galangina sobre a susceptibilidade às convulsões induzidas por pentilenotetrazol na presença de prostaglandina E2 |
title_full |
Efeito do flavonoide galangina sobre a susceptibilidade às convulsões induzidas por pentilenotetrazol na presença de prostaglandina E2 |
title_fullStr |
Efeito do flavonoide galangina sobre a susceptibilidade às convulsões induzidas por pentilenotetrazol na presença de prostaglandina E2 |
title_full_unstemmed |
Efeito do flavonoide galangina sobre a susceptibilidade às convulsões induzidas por pentilenotetrazol na presença de prostaglandina E2 |
title_sort |
Efeito do flavonoide galangina sobre a susceptibilidade às convulsões induzidas por pentilenotetrazol na presença de prostaglandina E2 |
author |
Zorzi, Viviane Nogueira de |
author_facet |
Zorzi, Viviane Nogueira de |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Fighera, Michele Rechia |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/8583392747509231 |
dc.contributor.referee1.fl_str_mv |
Oliveira, Clarissa Vasconcelos de |
dc.contributor.referee2.fl_str_mv |
Souza, Mauren Assis de |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/8634796247382371 |
dc.contributor.author.fl_str_mv |
Zorzi, Viviane Nogueira de |
contributor_str_mv |
Fighera, Michele Rechia Oliveira, Clarissa Vasconcelos de Souza, Mauren Assis de |
dc.subject.por.fl_str_mv |
Neuroinflamação Prostaglandina E2 Susceptibilidade Crises epilépticas Galangina Córtex cerebral |
topic |
Neuroinflamação Prostaglandina E2 Susceptibilidade Crises epilépticas Galangina Córtex cerebral Neuroinflammation Prostaglandin E2 Susceptibility Seizures Galangin Cerebral cortex CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
dc.subject.eng.fl_str_mv |
Neuroinflammation Prostaglandin E2 Susceptibility Seizures Galangin Cerebral cortex |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Epilepsy is one of the most common chronic neurological diseases, characterized by recurrent epileptic seizures, where one-third of patients are refractory to existing treatments. Evidences have revealed association between neuroinflammation and increased susceptibility to seizures since there is a pronounced increase in the expression of key inflammatory mediators, such as prostaglandin E2 (PGE2) during seizures. The PGE2 has been demonstrated to stimulate the release of glutamate and to inhibit Na+ K+ -ATPase enzyme, which in fact may increase neuronal excitability, contributing to seizure. Knowing the important role of inflammation during seizures and existence of refractory to anticonvulsant treatment, the purpose initial of the present study was to investigate whether PGE2 increases to susceptibility to seizures induced by pentylenetetrazol (PTZ). Subsequently, we evaluate whether a compound isolated from the Piper aleyreanum plant, named Galangin, proved to be anti- inflammatory and protective in a nociception model induced by glutamate and PGE2, could have anticonvulsive activity in this study. For this, in the experiment 1, the mice were injected with PGE2 (100ng/2μl; intracerebroventricular (i.c.v.) and fifteen minutes later were injected with a subefective PTZ dose (35mg/kg, intraperitoneal (i.p) for evaluation of susceptibility to seizures. In the experiment 2, the mice were injected with Galangin (30mg/kg; i.p.) fifteen minutes before PGE2 injection, fifteen minutes later were injected with PTZ, in the same doses. Our results showed that the group treated com PGE2 increased the susceptibility to PTZ, causing myoclonic and generalized seizures, increasing the seizures duration and electroencephalographic wave amplitude. Furthermore, statistical analyzes showed that the treatment with PGE2 or PGE2 and PTZ combined increased IBA-1 (microglial marker), GFAP (astrocytic marker), 4-HNE (lipid peroxidation marker), VCAM-1 (vascular cell adhesion molecule 1) and p-PKAIIα (phosphorylated cAMP-dependent protein kinase) immunocontents. However, nor PTZ or PGE2 treatment changed the immunocontent of receptors of PGE2 (EP1, EP2 and EP3). Indeed, pre-treatment with Galangin prevented the convulsive behavior and decreased electroencephalographic wave amplitude as well as prevented reactive species production, microglial and astrocytic activation, decreased VCAM-1 immunocontent and phosphorylation state of PKAIIα induced by PGE2/PTZ. Therefore, this study suggests that the compound Galangin presented anticonvulsive and anti-inflammatory activities against the behavioral and neurochemical changes induced by administration of PGE2 and PTZ. However, further studies are needed to investigate the clinical implications of these findings and their underlying mechanisms. |
publishDate |
2018 |
dc.date.issued.fl_str_mv |
2018-03-24 |
dc.date.accessioned.fl_str_mv |
2021-07-19T17:24:22Z |
dc.date.available.fl_str_mv |
2021-07-19T17:24:22Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/masterThesis |
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masterThesis |
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http://repositorio.ufsm.br/handle/1/21515 |
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http://repositorio.ufsm.br/handle/1/21515 |
dc.language.iso.fl_str_mv |
por |
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por |
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200800000002 |
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600 600 600 |
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Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Naturais e Exatas |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Bioquímica |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Naturais e Exatas |
dc.source.none.fl_str_mv |
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bitstream.checksum.fl_str_mv |
2f0571ecee68693bd5cd3f17c1e075df f6fd8eb05051e5ba82e8eeb6dd08e50f 4460e5956bc1d1639be9ae6146a50347 134d7f215a1b45cc1648536d2bac26bc b2a9b5a0b3b55c1e5d1885f60f106721 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositório Institucional Manancial UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
ouvidoria@ufsm.br |
_version_ |
1808854730827366400 |