Prostaglandina E2 potencializa as convulsões induzidas por metilmalonato
Autor(a) principal: | |
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Data de Publicação: | 2009 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional Manancial UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/8943 |
Resumo: | Methylmalonic acidemias comprehend a group of innate error of the metabolism (EIM)characterized clinically and biochemically for the tissue accumulation of acid methylmalonic (MMA)and neurological dysfunction, including seizures. The clinical experience suggests that infections precipitate metabolic crises in methylmalonic acidemic patients. Since it has been demonstrated that MMA cause seizures, and that inflammation facilitates the occurrence of seizures in some animal models, is possible that inflammatory mediators, such as the prostaglandins, also facilitate MMAinduced seizures. Ciclooxigenase (COX) is the rate-limiting enzyme in the metabolic route by which the arachidonic acid is converted to prostaglandins. COX-2 is an isoform of cicloooxigenase that is induced at sites of injury / inflammation, and that is also constitutively expressed in some tissues, such as the central nervous system (CNS). It has been suggested that prostaglandin E2 (PGE2), the main product of COX-2 in the CNS, plays an important role in some neurodegenerative diseases, including epilepsy. However, no study has evaluated whether inflammatory mediators, such as the PGE2, facilitates MMA-induced seizures, to date. Thus, in this study we investigated the role of COX-2 and of PGE2 in seizures induced by MMA (2,5 µmol/2,5 µL, i.c.v.). While PGE2 (100 ng/2 μL, i.c.v.) facilitated, the selective COX-2 inhibitor celecoxib, attenuated MMA-induced seizures, assessed by electroencephalographic recordings in the hippocampus and cerebral cortex of rats. The ´protective effect of celecoxib against MMA-induced seizures was prevented by the PGE2. The results of this study support a facilitatory role for COX-2/PGE2 pathway in the MMA-induced seizures. |
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2010-03-012010-03-012009-11-23SALVADORI, Mirian Graciela da Silva Stiebbe. PROSTAGLANDIN E2 POTENTIATES METHYLMALONATE-INDUCED SEIZURES. 2009. 103 f. Dissertação (Mestrado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2009.http://repositorio.ufsm.br/handle/1/8943Methylmalonic acidemias comprehend a group of innate error of the metabolism (EIM)characterized clinically and biochemically for the tissue accumulation of acid methylmalonic (MMA)and neurological dysfunction, including seizures. The clinical experience suggests that infections precipitate metabolic crises in methylmalonic acidemic patients. Since it has been demonstrated that MMA cause seizures, and that inflammation facilitates the occurrence of seizures in some animal models, is possible that inflammatory mediators, such as the prostaglandins, also facilitate MMAinduced seizures. Ciclooxigenase (COX) is the rate-limiting enzyme in the metabolic route by which the arachidonic acid is converted to prostaglandins. COX-2 is an isoform of cicloooxigenase that is induced at sites of injury / inflammation, and that is also constitutively expressed in some tissues, such as the central nervous system (CNS). It has been suggested that prostaglandin E2 (PGE2), the main product of COX-2 in the CNS, plays an important role in some neurodegenerative diseases, including epilepsy. However, no study has evaluated whether inflammatory mediators, such as the PGE2, facilitates MMA-induced seizures, to date. Thus, in this study we investigated the role of COX-2 and of PGE2 in seizures induced by MMA (2,5 µmol/2,5 µL, i.c.v.). While PGE2 (100 ng/2 μL, i.c.v.) facilitated, the selective COX-2 inhibitor celecoxib, attenuated MMA-induced seizures, assessed by electroencephalographic recordings in the hippocampus and cerebral cortex of rats. The ´protective effect of celecoxib against MMA-induced seizures was prevented by the PGE2. The results of this study support a facilitatory role for COX-2/PGE2 pathway in the MMA-induced seizures.A acidemia metilmalônica é um erro inato do metabolismo (EIM) caracterizado bioquimicamente e clinicamente pelo acúmulo tecidual de ácido metilmalônico (MMA) e disfunção neurológica, que inclui convulsões. A experiência clínica sugere que infecções precipitam crises metabólicas em pacientes metilmalonicacidêmicos. À medida em que foi demonstrado que o MMA causa convulsões, e que a inflamação pode contribuir para a ocorrência de convulsões em vários modelos animais, é possível que mediadores inflamatórios, como as prostaglandinas, facilitem as convulsões induzidas por MMA. A ciclooxigenase (COX) é a enzima marca-passo na rota metabólica pela qual o ácido araquidônico é convertido em prostaglandinas, e a COX-2 uma isoforma da cicloooxigenase, é induzida em sítios de lesão/inflamação, e também se expressa constituivamente em alguns tecidos, como o sistema nervoso central (SNC). Tem sido sugerido que a prostaglandina E2 (PGE2), principal produto da via COX-2 no SNC, tenha um papel importante em várias doenças neurodegenerativas, incluindo epilepsia. Contudo, até a presente data nenhum estudo avaliou se mediadores inflamatórios, como a PGE2, facilitam as convulsões induzidas por MMA. Assim, neste estudo investigamos o papel da COX-2 e da PGE2 nas convulsões induzidas por MMA (2,5 µmol/2,5 µL, i.c.v.). Verificamos que a PGE2 (100 ng/2 μL, i.c.v.) facilita as convulsões induzidas por este ácido orgânico. Além disso, verificamos que o celecoxibe, um inibidor seletivo da COX-2, na dose de 2 mg/kg (v.o.), atenuou as convulsões comportamentais e eletrográficas induzidas por MMA no hipocampo e córtex cerebral de ratos. O efeito protetor do celecoxibe contra as convulsões induzidas por MMA foi revertido pela administração i.c.v. de prostaglandina E2. O conjunto de dados deste estudo suporta um papel facilitatório para a via COX-2/PGE2 nas convulsões induzidas por MMA.Conselho Nacional de Desenvolvimento Científico e Tecnológicoapplication/pdfporUniversidade Federal de Santa MariaPrograma de Pós-Graduação em FarmacologiaUFSMBRFarmacologiaMetilmalonatoConvulsõesInflamaçãoProstaglandina E2CelecoxibeMethylmalonateSeizuresInflammationProstaglandin E2CelecoxibCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIAProstaglandina E2 potencializa as convulsões induzidas por metilmalonatoProstaglandin E2 potentiates methylmalonate-induced seizuresinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisMello, Carlos Fernando dehttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4782674D2Almeida, Reinaldo Nobrega dehttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4780011U4Furian, Ana Fláviahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4705849T6http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4717176Z4Salvadori, Mirian Graciela da Silva Stiebbe20100000000040050030030050082e537b0-4a43-400e-9f82-0cd91952adea8134f2de-3803-4a2b-8c76-479957033f9c229d3530-816e-44af-86bc-de4e2de82ddbccd57a08-6ff7-4098-88ec-5cb936e92f93info:eu-repo/semantics/openAccessreponame:Repositório Institucional Manancial UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALSALVADORI, MIRIAN GRACIELA DA SILVA STIEBBE.pdfapplication/pdf4621698http://repositorio.ufsm.br/bitstream/1/8943/1/SALVADORI%2c%20MIRIAN%20GRACIELA%20DA%20SILVA%20STIEBBE.pdf5290ea8354a0d3b91ed67cae73884b2eMD51TEXTSALVADORI, MIRIAN GRACIELA DA SILVA STIEBBE.pdf.txtSALVADORI, MIRIAN GRACIELA DA SILVA STIEBBE.pdf.txtExtracted texttext/plain167226http://repositorio.ufsm.br/bitstream/1/8943/2/SALVADORI%2c%20MIRIAN%20GRACIELA%20DA%20SILVA%20STIEBBE.pdf.txtaa4870a264417ce2c8617e868ed81ad0MD52THUMBNAILSALVADORI, MIRIAN GRACIELA DA SILVA STIEBBE.pdf.jpgSALVADORI, MIRIAN GRACIELA DA SILVA STIEBBE.pdf.jpgIM Thumbnailimage/jpeg5819http://repositorio.ufsm.br/bitstream/1/8943/3/SALVADORI%2c%20MIRIAN%20GRACIELA%20DA%20SILVA%20STIEBBE.pdf.jpgcae60f1839dfdb250c2c5ab48af699f2MD531/89432022-03-17 10:56:41.607oai:repositorio.ufsm.br:1/8943Repositório Institucionalhttp://repositorio.ufsm.br/PUBhttp://repositorio.ufsm.br/oai/requestouvidoria@ufsm.bropendoar:39132022-03-17T13:56:41Repositório Institucional Manancial UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.por.fl_str_mv |
Prostaglandina E2 potencializa as convulsões induzidas por metilmalonato |
dc.title.alternative.eng.fl_str_mv |
Prostaglandin E2 potentiates methylmalonate-induced seizures |
title |
Prostaglandina E2 potencializa as convulsões induzidas por metilmalonato |
spellingShingle |
Prostaglandina E2 potencializa as convulsões induzidas por metilmalonato Salvadori, Mirian Graciela da Silva Stiebbe Metilmalonato Convulsões Inflamação Prostaglandina E2 Celecoxibe Methylmalonate Seizures Inflammation Prostaglandin E2 Celecoxib CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
title_short |
Prostaglandina E2 potencializa as convulsões induzidas por metilmalonato |
title_full |
Prostaglandina E2 potencializa as convulsões induzidas por metilmalonato |
title_fullStr |
Prostaglandina E2 potencializa as convulsões induzidas por metilmalonato |
title_full_unstemmed |
Prostaglandina E2 potencializa as convulsões induzidas por metilmalonato |
title_sort |
Prostaglandina E2 potencializa as convulsões induzidas por metilmalonato |
author |
Salvadori, Mirian Graciela da Silva Stiebbe |
author_facet |
Salvadori, Mirian Graciela da Silva Stiebbe |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Mello, Carlos Fernando de |
dc.contributor.advisor1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4782674D2 |
dc.contributor.referee1.fl_str_mv |
Almeida, Reinaldo Nobrega de |
dc.contributor.referee1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4780011U4 |
dc.contributor.referee2.fl_str_mv |
Furian, Ana Flávia |
dc.contributor.referee2Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4705849T6 |
dc.contributor.authorLattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4717176Z4 |
dc.contributor.author.fl_str_mv |
Salvadori, Mirian Graciela da Silva Stiebbe |
contributor_str_mv |
Mello, Carlos Fernando de Almeida, Reinaldo Nobrega de Furian, Ana Flávia |
dc.subject.por.fl_str_mv |
Metilmalonato Convulsões Inflamação Prostaglandina E2 Celecoxibe |
topic |
Metilmalonato Convulsões Inflamação Prostaglandina E2 Celecoxibe Methylmalonate Seizures Inflammation Prostaglandin E2 Celecoxib CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
dc.subject.eng.fl_str_mv |
Methylmalonate Seizures Inflammation Prostaglandin E2 Celecoxib |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
description |
Methylmalonic acidemias comprehend a group of innate error of the metabolism (EIM)characterized clinically and biochemically for the tissue accumulation of acid methylmalonic (MMA)and neurological dysfunction, including seizures. The clinical experience suggests that infections precipitate metabolic crises in methylmalonic acidemic patients. Since it has been demonstrated that MMA cause seizures, and that inflammation facilitates the occurrence of seizures in some animal models, is possible that inflammatory mediators, such as the prostaglandins, also facilitate MMAinduced seizures. Ciclooxigenase (COX) is the rate-limiting enzyme in the metabolic route by which the arachidonic acid is converted to prostaglandins. COX-2 is an isoform of cicloooxigenase that is induced at sites of injury / inflammation, and that is also constitutively expressed in some tissues, such as the central nervous system (CNS). It has been suggested that prostaglandin E2 (PGE2), the main product of COX-2 in the CNS, plays an important role in some neurodegenerative diseases, including epilepsy. However, no study has evaluated whether inflammatory mediators, such as the PGE2, facilitates MMA-induced seizures, to date. Thus, in this study we investigated the role of COX-2 and of PGE2 in seizures induced by MMA (2,5 µmol/2,5 µL, i.c.v.). While PGE2 (100 ng/2 μL, i.c.v.) facilitated, the selective COX-2 inhibitor celecoxib, attenuated MMA-induced seizures, assessed by electroencephalographic recordings in the hippocampus and cerebral cortex of rats. The ´protective effect of celecoxib against MMA-induced seizures was prevented by the PGE2. The results of this study support a facilitatory role for COX-2/PGE2 pathway in the MMA-induced seizures. |
publishDate |
2009 |
dc.date.issued.fl_str_mv |
2009-11-23 |
dc.date.accessioned.fl_str_mv |
2010-03-01 |
dc.date.available.fl_str_mv |
2010-03-01 |
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info:eu-repo/semantics/masterThesis |
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masterThesis |
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publishedVersion |
dc.identifier.citation.fl_str_mv |
SALVADORI, Mirian Graciela da Silva Stiebbe. PROSTAGLANDIN E2 POTENTIATES METHYLMALONATE-INDUCED SEIZURES. 2009. 103 f. Dissertação (Mestrado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2009. |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/8943 |
identifier_str_mv |
SALVADORI, Mirian Graciela da Silva Stiebbe. PROSTAGLANDIN E2 POTENTIATES METHYLMALONATE-INDUCED SEIZURES. 2009. 103 f. Dissertação (Mestrado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2009. |
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