Efeito do ácido rosmarínico sobre as crises epilépticas e alterações comportamentais em diferentes modelos experimentais de epilepsia
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/17987 |
Resumo: | Epilepsy is a chronic neurological disease characterized by recurrent seizures. Current anticonvulsant drugs are ineffective in nearly one third of patients and may cause significant adverse effects. Rosmarinic acid is a naturally-occurring substance which displays several biological effects including antioxidant, anti inflammatory and neuroprotective activity. Since oxidative stress, inflammation and excitotoxicity play a role in the pathophysiology of seizures, we aimed the present study to test the hypothesis that rosmarinic acid displays anticonvulsant effects in different experimental models. Our results demonstrate that rosmarinic acid at the dose of 30 mg/kg increased the latencies to myoclonic and generalized seizures induced by PTZ and myoclonic seizures induced by pilocarpine. These data were confirmed by encephalographic recordings. Furthermore, the anticonvulsant dose of rosmarinic acid was anxiolytic, since it increased the number of crossings and the time of exploration in the center of open field. In the forced swimming test rosmarinic acid increased the immobility time. In another set of experiments, we evaluated the effects of sub-chronic treatment of rosmarinic acid (30 mg/kg) on epileptic seizures and behavioral changes in epilepsy model induced by pilocarpine. However, the treatment with rosmarinic acid caused no significant changes in the frequency of seizures nor in the behavioral comorbities evaluated. These results probably reflect the GABAergic action of rosmarinic acid, by inhibiting the enzyme GABA- transaminase, since it was anticonvulsant and anxiolytic activity in the acute protocols. However, anticonvulsant effect and/or disease-modifying effects were seen in the chronic model of epilepsy. Further studies are needed to investigate the clinical implications of these findings and their underlying mechanisms. |
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Efeito do ácido rosmarínico sobre as crises epilépticas e alterações comportamentais em diferentes modelos experimentais de epilepsiaEffect of rosmarinic acid on seizures epileptic and behavioral change in different models experimental of epilepsyEpilepsiaComportamentoAtividade anticonvulsivanteÁcido rosmarínicoAtividade ansiolíticaEpilepsyBehaviorAnticonvulsant activityRosmarinic acidAnxiolytic activityCNPQ::CIENCIAS DA SAUDE::FARMACIAEpilepsy is a chronic neurological disease characterized by recurrent seizures. Current anticonvulsant drugs are ineffective in nearly one third of patients and may cause significant adverse effects. Rosmarinic acid is a naturally-occurring substance which displays several biological effects including antioxidant, anti inflammatory and neuroprotective activity. Since oxidative stress, inflammation and excitotoxicity play a role in the pathophysiology of seizures, we aimed the present study to test the hypothesis that rosmarinic acid displays anticonvulsant effects in different experimental models. Our results demonstrate that rosmarinic acid at the dose of 30 mg/kg increased the latencies to myoclonic and generalized seizures induced by PTZ and myoclonic seizures induced by pilocarpine. These data were confirmed by encephalographic recordings. Furthermore, the anticonvulsant dose of rosmarinic acid was anxiolytic, since it increased the number of crossings and the time of exploration in the center of open field. In the forced swimming test rosmarinic acid increased the immobility time. In another set of experiments, we evaluated the effects of sub-chronic treatment of rosmarinic acid (30 mg/kg) on epileptic seizures and behavioral changes in epilepsy model induced by pilocarpine. However, the treatment with rosmarinic acid caused no significant changes in the frequency of seizures nor in the behavioral comorbities evaluated. These results probably reflect the GABAergic action of rosmarinic acid, by inhibiting the enzyme GABA- transaminase, since it was anticonvulsant and anxiolytic activity in the acute protocols. However, anticonvulsant effect and/or disease-modifying effects were seen in the chronic model of epilepsy. Further studies are needed to investigate the clinical implications of these findings and their underlying mechanisms.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESA epilepsia é uma doença neurológica crônica caracterizada por crises epilépticas recorrentes. No entanto, as atuais drogas anticonvulsivantes são ineficazes em quase um terço dos pacientes e podem causar efeitos adversos significativos. O ácido rosmarínico é uma substancia natural, que exibe diversos efeitos biológicos, incluindo atividade antioxidante, anti-inflamatória e neuroprotetora. Frente ao fato que o estresse oxidativo, a inflamação e excitotoxicidade desempenham um papel importante na fisiopatologia das crises, nós buscamos neste presente estudo testar a hipótese que o ácido rosmarínico exibe efeitos anticonvulsivantes em diferentes modelos experimentais. Nossos resultados demostraram que o ácido rosmarínico quando administrado na dose de 30 mg/kg aumenta a latência para as crises mioclônicas e para as crises generalizadas tônico-clonicas induzidas por PTZ, assim como aumentou a latência para as crises mioclônicas induzidas pelo agente convulsivo Pilocarpina. Estes dados foram confirmados através do registro eletroencefalográfico. Além disso, a dose anticonvulsivante de ácido rosmarínico (30 mg/kg) aumentou o número de crossing e o tempo exploração centro da arena no teste campo aberto, sugerindo efeito tipo ansiolítico. No teste do nado forçado ocorreu um aumento no tempo de imobilidade dos animais. Posteriormente foi avaliado o efeito do tratamento sub-crônico do ácido rosmarínico (3 ou 30 mg/Kg) sobre as crises epilépticas e alterações comportamentais no modelo de status epilepticus induzido por Pilocarpina. No entanto o ácido rosmarínico não causou nenhuma diferença significativa na frequência das crises e nem nos parâmetros comportamentais avaliados. Esses resultados decorrem possivelmente da ação GABAergica do ácido rosmarínico, através da inibição da enzima GABA-transaminase, que culmina em uma atividade anticonvulsivante e ansiolítica no modelo agudo de epilepsia. No entanto, não foi possível visualizar o efeito anticonvulsivante e/ou alterações comportamentais no modelo crônico de epilepsia. Todavia, estudos adicionais são necessários para investigar as implicações clínicas destes achados, bem como os seus mecanismos subjacentes.Universidade Federal de Santa MariaBrasilFarmacologiaUFSMPrograma de Pós-Graduação em FarmacologiaCentro de Ciências da SaúdeOliveira, Mauro Schneiderhttp://lattes.cnpq.br/7132934163734175Oliveira, Sara Marchesan dehttp://lattes.cnpq.br/6574555059806902Calcagnotto, Maria Elisahttp://lattes.cnpq.br/0585587827221284Grigoletto, Jéssica2019-08-21T21:33:19Z2019-08-21T21:33:19Z2016-03-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/17987porAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2019-08-22T06:01:24Zoai:repositorio.ufsm.br:1/17987Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2019-08-22T06:01:24Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Efeito do ácido rosmarínico sobre as crises epilépticas e alterações comportamentais em diferentes modelos experimentais de epilepsia Effect of rosmarinic acid on seizures epileptic and behavioral change in different models experimental of epilepsy |
title |
Efeito do ácido rosmarínico sobre as crises epilépticas e alterações comportamentais em diferentes modelos experimentais de epilepsia |
spellingShingle |
Efeito do ácido rosmarínico sobre as crises epilépticas e alterações comportamentais em diferentes modelos experimentais de epilepsia Grigoletto, Jéssica Epilepsia Comportamento Atividade anticonvulsivante Ácido rosmarínico Atividade ansiolítica Epilepsy Behavior Anticonvulsant activity Rosmarinic acid Anxiolytic activity CNPQ::CIENCIAS DA SAUDE::FARMACIA |
title_short |
Efeito do ácido rosmarínico sobre as crises epilépticas e alterações comportamentais em diferentes modelos experimentais de epilepsia |
title_full |
Efeito do ácido rosmarínico sobre as crises epilépticas e alterações comportamentais em diferentes modelos experimentais de epilepsia |
title_fullStr |
Efeito do ácido rosmarínico sobre as crises epilépticas e alterações comportamentais em diferentes modelos experimentais de epilepsia |
title_full_unstemmed |
Efeito do ácido rosmarínico sobre as crises epilépticas e alterações comportamentais em diferentes modelos experimentais de epilepsia |
title_sort |
Efeito do ácido rosmarínico sobre as crises epilépticas e alterações comportamentais em diferentes modelos experimentais de epilepsia |
author |
Grigoletto, Jéssica |
author_facet |
Grigoletto, Jéssica |
author_role |
author |
dc.contributor.none.fl_str_mv |
Oliveira, Mauro Schneider http://lattes.cnpq.br/7132934163734175 Oliveira, Sara Marchesan de http://lattes.cnpq.br/6574555059806902 Calcagnotto, Maria Elisa http://lattes.cnpq.br/0585587827221284 |
dc.contributor.author.fl_str_mv |
Grigoletto, Jéssica |
dc.subject.por.fl_str_mv |
Epilepsia Comportamento Atividade anticonvulsivante Ácido rosmarínico Atividade ansiolítica Epilepsy Behavior Anticonvulsant activity Rosmarinic acid Anxiolytic activity CNPQ::CIENCIAS DA SAUDE::FARMACIA |
topic |
Epilepsia Comportamento Atividade anticonvulsivante Ácido rosmarínico Atividade ansiolítica Epilepsy Behavior Anticonvulsant activity Rosmarinic acid Anxiolytic activity CNPQ::CIENCIAS DA SAUDE::FARMACIA |
description |
Epilepsy is a chronic neurological disease characterized by recurrent seizures. Current anticonvulsant drugs are ineffective in nearly one third of patients and may cause significant adverse effects. Rosmarinic acid is a naturally-occurring substance which displays several biological effects including antioxidant, anti inflammatory and neuroprotective activity. Since oxidative stress, inflammation and excitotoxicity play a role in the pathophysiology of seizures, we aimed the present study to test the hypothesis that rosmarinic acid displays anticonvulsant effects in different experimental models. Our results demonstrate that rosmarinic acid at the dose of 30 mg/kg increased the latencies to myoclonic and generalized seizures induced by PTZ and myoclonic seizures induced by pilocarpine. These data were confirmed by encephalographic recordings. Furthermore, the anticonvulsant dose of rosmarinic acid was anxiolytic, since it increased the number of crossings and the time of exploration in the center of open field. In the forced swimming test rosmarinic acid increased the immobility time. In another set of experiments, we evaluated the effects of sub-chronic treatment of rosmarinic acid (30 mg/kg) on epileptic seizures and behavioral changes in epilepsy model induced by pilocarpine. However, the treatment with rosmarinic acid caused no significant changes in the frequency of seizures nor in the behavioral comorbities evaluated. These results probably reflect the GABAergic action of rosmarinic acid, by inhibiting the enzyme GABA- transaminase, since it was anticonvulsant and anxiolytic activity in the acute protocols. However, anticonvulsant effect and/or disease-modifying effects were seen in the chronic model of epilepsy. Further studies are needed to investigate the clinical implications of these findings and their underlying mechanisms. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-03-01 2019-08-21T21:33:19Z 2019-08-21T21:33:19Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/17987 |
url |
http://repositorio.ufsm.br/handle/1/17987 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Farmacologia UFSM Programa de Pós-Graduação em Farmacologia Centro de Ciências da Saúde |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Farmacologia UFSM Programa de Pós-Graduação em Farmacologia Centro de Ciências da Saúde |
dc.source.none.fl_str_mv |
reponame:Manancial - Repositório Digital da UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Manancial - Repositório Digital da UFSM |
collection |
Manancial - Repositório Digital da UFSM |
repository.name.fl_str_mv |
Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
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1805922043130019840 |