Ação farmacológica do 3-alquinil selenofeno em modelos de convulsão em ratos jovens

Detalhes bibliográficos
Autor(a) principal: Wilhelm, Ethel Antunes
Data de Publicação: 2012
Tipo de documento: Tese
Idioma: por
Título da fonte: Manancial - Repositório Digital da UFSM
dARK ID: ark:/26339/0013000015v54
Texto Completo: http://repositorio.ufsm.br/handle/1/4453
Resumo: Seizures have important consequences in terms of mortality and quality of life of the affected population, being a risk factor for the development of cognitive and behavioral abnormalities. Considering the promising pharmacological properties of molecules containing selenium, in article 1, we evaluated the anticonvulsant action of 1-(2,5-diphenylselenophen-3-yl)-3-methylpent-1-yn-3-ol, generically called 3-alkynyl selenophene (3-ASP) against seizures induced by pilocarpine (PC), pentylenetetrazole (PTZ) and kainate (KA) in 21-days-old rats. Animals were pre-treated with 3-ASP (10, 25 or 50 mg/kg; per oral, p.o.) or vehicle, 30 minutes before of intraperitoneally administration of PC (400 mg/kg), PTZ (80 mg/kg) or KA (45 mg/kg). 3-ASP pre-treatment (50 mg/kg) abolished seizures and the death induced by PC administration. 3-ASP (50 mg/kg) increased the latency to the first convulsive episode, as well as decreased the mortality and incidence of seizures caused by PTZ and KA. In article 1, the antioxidant activity of 3-ASP (10, 25 or 50 mg/kg; p.o.) against the oxidative stress induced by PC (400 mg/kg, i.p.) in 21-days-old rats was evaluated. Our results demonstrated that 3-ASP pre-treatment was effective in protecting against the inhibition of cerebral activity of superoxide dismutase, decreased ascorbic acid levels, stimulation of catalase activity and increase of reactive species levels caused by PC. Additionally, 3-ASP protected against the inhibition of acetylcholinesterase and Na+, K+-ATPase activities resulting from convulsions induced by PC. The involvement of glutamatergic and GABAergic systems in the anticonvulsant action of 3-ASP was investigated (Articles 1 and 2). The combination of sub-effective doses of 3-ASP (10 mg/kg, p.o.) and diazepam (GABA agonist; 0,5 mg/kg, i.p.), 5S,10R-(+)-5-methyl-10,11-dihydro- 5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist; 0.1mg/kg, i.p.) or 6,7-dinitroquinoxaline-2,3-dione (DNQX, a non-NMDA receptor antagonist; 5 mg/kg, i.p.) was effective in increasing the latency to the first convulsive episode, as well as, in decreasing the incidence of convulsions induced by PC. On the other hand, the combination of 3-ASP and 2-methyl-6-phenylethynyl pyridine hydrochloride (MPEP, an antagonist of metabotropic glutamate receptor mGluR5; 0,5 mg/kg, i.p.) did not protect against convulsions. The oral administration of 3-ASP (50 mg/kg) caused an inhibition of 64% and 58% of GABA uptake in the cortex and hippocampus, respectively. However, no change in glutamate uptake after 3-ASP administration (50 mg/kg) was found. Additionally, in article 2, we investigated the possible interaction between sub-effective doses of 3-ASP and GABA uptake or GABA transaminase (GABA-T) inhibitors against PC-induced seizures in 21-days-old rats. To this, sub-effective doses of 3-ASP (10 mg/kg; p.o.) and DL-2,4-diamino-n-butyric acid hydrochloride (DABA, an inhibitor of GABA uptake; 2 mg/kg; i.p.) or aminooxyacetic acid hemihydrochloride (AOAA; a GABA-T inhibitor; 10 mg/kg, i.p.) were co-administrated in 21-days-old rats before of PC administration (400 mg/kg). The treatment with 3-ASP and DABA abolished the PC-induced seizures. Similar results were found when sub-effective doses of 3-ASP and AOAA were administrated in 21-days-old rats. Finally, in the article 3 we investigated the effect of 3-ASP or diazepam against convulsions, the increased susceptibility to the development of seizures and long term memory impairment resulting from febrile seizures induced by hyperthermia. 21-Days-old rats were pre-treated with 3-ASP (25, 50 or 100 mg/kg; p.o), diazepam (1 or 5 mg/kg; i.p.) or vehicle. After the treatment, animals were exposed to a stream of heated air to approximately 41°C. Thirty days after the exposure to hyperthermia, the susceptibility to the development of seizures and long term memory impairment were evaluated. We verified that the pre-treatment with 3-ASP or diazepam did not protect against stereotyped behavior, facial automatisms and body flexion induced by hyperthermia. The protective effect of 3-ASP (100 mg/kg) against the increased susceptibility to the development of seizures and long term memory impairment resulting from febrile seizures induced by hyperthermia was demonstrated. Diazepam (1 or 5 mg/kg) did not protect against long term memory impairment caused by febrile seizures. In addition, diazepam (1 mg/kg) treatment caused a significant cognitive impairment in animals kept at room temperature. These results suggest that 3-ASP had anticonvulsant action in 21-days-old rats and that this action appears to be mediated by glutamatergic and GABAergic systems. In addition, the anticonvulsant action of 3-ASP seems to be associated with its antioxidant activity. Finally, 3-ASP can represent an important tool to protect against increased susceptibility to seizures and cognitive impairment resulting from febrile seizures.
id UFSM_3c8012cbaf8d8aecf9a0a2f4239fc382
oai_identifier_str oai:repositorio.ufsm.br:1/4453
network_acronym_str UFSM
network_name_str Manancial - Repositório Digital da UFSM
repository_id_str
spelling Ação farmacológica do 3-alquinil selenofeno em modelos de convulsão em ratos jovensPharmacological action of 3-alkynyl selenophene on models of seizures in rat pups3-alquinil selenofenoSelênioAnticonvulsivanteHipertermiaEstresse oxidativoÁcido γ-aminobutíricoGlutamato3-alkynyl selenopheneSeleniumAnticonvulsantHiperthermiaOxidative stressγ-aminobutyric acidGlutamateCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICASeizures have important consequences in terms of mortality and quality of life of the affected population, being a risk factor for the development of cognitive and behavioral abnormalities. Considering the promising pharmacological properties of molecules containing selenium, in article 1, we evaluated the anticonvulsant action of 1-(2,5-diphenylselenophen-3-yl)-3-methylpent-1-yn-3-ol, generically called 3-alkynyl selenophene (3-ASP) against seizures induced by pilocarpine (PC), pentylenetetrazole (PTZ) and kainate (KA) in 21-days-old rats. Animals were pre-treated with 3-ASP (10, 25 or 50 mg/kg; per oral, p.o.) or vehicle, 30 minutes before of intraperitoneally administration of PC (400 mg/kg), PTZ (80 mg/kg) or KA (45 mg/kg). 3-ASP pre-treatment (50 mg/kg) abolished seizures and the death induced by PC administration. 3-ASP (50 mg/kg) increased the latency to the first convulsive episode, as well as decreased the mortality and incidence of seizures caused by PTZ and KA. In article 1, the antioxidant activity of 3-ASP (10, 25 or 50 mg/kg; p.o.) against the oxidative stress induced by PC (400 mg/kg, i.p.) in 21-days-old rats was evaluated. Our results demonstrated that 3-ASP pre-treatment was effective in protecting against the inhibition of cerebral activity of superoxide dismutase, decreased ascorbic acid levels, stimulation of catalase activity and increase of reactive species levels caused by PC. Additionally, 3-ASP protected against the inhibition of acetylcholinesterase and Na+, K+-ATPase activities resulting from convulsions induced by PC. The involvement of glutamatergic and GABAergic systems in the anticonvulsant action of 3-ASP was investigated (Articles 1 and 2). The combination of sub-effective doses of 3-ASP (10 mg/kg, p.o.) and diazepam (GABA agonist; 0,5 mg/kg, i.p.), 5S,10R-(+)-5-methyl-10,11-dihydro- 5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist; 0.1mg/kg, i.p.) or 6,7-dinitroquinoxaline-2,3-dione (DNQX, a non-NMDA receptor antagonist; 5 mg/kg, i.p.) was effective in increasing the latency to the first convulsive episode, as well as, in decreasing the incidence of convulsions induced by PC. On the other hand, the combination of 3-ASP and 2-methyl-6-phenylethynyl pyridine hydrochloride (MPEP, an antagonist of metabotropic glutamate receptor mGluR5; 0,5 mg/kg, i.p.) did not protect against convulsions. The oral administration of 3-ASP (50 mg/kg) caused an inhibition of 64% and 58% of GABA uptake in the cortex and hippocampus, respectively. However, no change in glutamate uptake after 3-ASP administration (50 mg/kg) was found. Additionally, in article 2, we investigated the possible interaction between sub-effective doses of 3-ASP and GABA uptake or GABA transaminase (GABA-T) inhibitors against PC-induced seizures in 21-days-old rats. To this, sub-effective doses of 3-ASP (10 mg/kg; p.o.) and DL-2,4-diamino-n-butyric acid hydrochloride (DABA, an inhibitor of GABA uptake; 2 mg/kg; i.p.) or aminooxyacetic acid hemihydrochloride (AOAA; a GABA-T inhibitor; 10 mg/kg, i.p.) were co-administrated in 21-days-old rats before of PC administration (400 mg/kg). The treatment with 3-ASP and DABA abolished the PC-induced seizures. Similar results were found when sub-effective doses of 3-ASP and AOAA were administrated in 21-days-old rats. Finally, in the article 3 we investigated the effect of 3-ASP or diazepam against convulsions, the increased susceptibility to the development of seizures and long term memory impairment resulting from febrile seizures induced by hyperthermia. 21-Days-old rats were pre-treated with 3-ASP (25, 50 or 100 mg/kg; p.o), diazepam (1 or 5 mg/kg; i.p.) or vehicle. After the treatment, animals were exposed to a stream of heated air to approximately 41°C. Thirty days after the exposure to hyperthermia, the susceptibility to the development of seizures and long term memory impairment were evaluated. We verified that the pre-treatment with 3-ASP or diazepam did not protect against stereotyped behavior, facial automatisms and body flexion induced by hyperthermia. The protective effect of 3-ASP (100 mg/kg) against the increased susceptibility to the development of seizures and long term memory impairment resulting from febrile seizures induced by hyperthermia was demonstrated. Diazepam (1 or 5 mg/kg) did not protect against long term memory impairment caused by febrile seizures. In addition, diazepam (1 mg/kg) treatment caused a significant cognitive impairment in animals kept at room temperature. These results suggest that 3-ASP had anticonvulsant action in 21-days-old rats and that this action appears to be mediated by glutamatergic and GABAergic systems. In addition, the anticonvulsant action of 3-ASP seems to be associated with its antioxidant activity. Finally, 3-ASP can represent an important tool to protect against increased susceptibility to seizures and cognitive impairment resulting from febrile seizures.Conselho Nacional de Desenvolvimento Científico e TecnológicoAs convulsões têm conseqüências importantes em termos de mortalidade e qualidade de vida da população afetada, sendo um fator de risco para o desenvolvimento de alterações cognitivas e anormalidades comportamentais. Tendo em vista as promissoras propriedades farmacológicas das moléculas contendo selênio, no artigo 1 avaliamos a ação anticonvulsivante do (1-(2,5-difenilselenofeno-3-il)-3-metilpent-1-in-3-ol, que foi genericamente denominado de 3-alquinil selenofeno (3-ASP) frente as convulsões induzidas por pilocarpina (PC), pentilenotetrazole (PTZ) e cainato (KA) em ratos de 21 dias de vida. Os animais foram pré-tratados com 3-ASP (10, 25 ou 50 mg/kg; per oral, p.o.) ou veículo, 30 minutos antes da administração intraperitoneal (i.p.) de PC (400 mg/kg), PTZ (80 mg/kg) ou KA (45 mg/kg). Verificamos que o pré-tratamento com 3-ASP (50 mg/kg) aboliu as convulsões e a morte induzidas pela administração de PC. O 3-ASP (50 mg/kg) aumentou a latência para o primeiro episódio convulsivo, bem como, diminuiu a mortalidade e a incidência das convulsões causadas por PTZ e KA. Ainda no artigo 1, consideramos importante o estudo da ação antioxidante do 3-ASP (10, 25 e 50 mg/kg; p.o.) frente ao estresse oxidativo induzido pela PC (400 mg/kg, i.p.) em ratos de 21 dias de vida. Os resultados demonstraram que o pré-tratamento com 3-ASP mostrou-se eficaz na proteção contra a inibição da atividade cerebral da superóxido dismutase, diminuição dos níveis de ácido ascórbico, estimulação da atividade da catalase e aumento dos níveis de espécies reativas causadas pela PC. Adicionalmente, o 3-ASP protegeu contra a inibição da atividade da acetilcolinesterase e da Na+,K+-ATPase resultantes das convulsões induzidas pela PC. Em um segundo momento, o envolvimento dos sistemas glutamatérgico e GABAérgico na ação anticonvulsivante do 3-ASP foi verificado (Artigos 1 e 2). A combinação de doses sub-efetivas de 3-ASP (10 mg/kg, p.o.) e diazepam (agonista GABAérgico; 0,5 mg/kg, i.p.), 5S,10R (+)-5-metil-10,11-dihidro-5H-dibenzo [a,d] ciclohepteno -5,10- imina maleato (MK-801; antagonista não-competitivo do receptor NMDA; 0.1mg/kg, i.p.) ou 6,7-dinitroquinoxalina-2,3-diona (DNQX; antagonista de receptores não-NMDA; 5 mg/kg, i.p.) aumentou a latência para o primeiro episódio convulsivo, bem como diminuiu a incidência de convulsões induzidas pela PC. Por outro lado, a combinação de 3-ASP e 2-metil-6-feniletinil piridina hidroclorada (MPEP; antagonista do receptor glutamatérgico metabotrópico do tipo 5; 0,5 mg/kg, i.p.) não apresentou efeito protetor contra os episódios convulsivos. A administração oral de 3-ASP (50 mg/kg) causou uma inibição de 64% e 58% da captação de GABA no córtex e no hipocampo, respectivamente. Entretanto, nenhuma alteração na captação de glutamato após a administração de 3-ASP (50 mg/kg) foi observada. Adicionalmente, no artigo 2 investigamos a possível interação entre doses sub-efetivas de 3-ASP e inibidores da captação de GABA ou da GABA transaminase (GABA-T) frente às convulsões induzidas por PC em ratos de 21 dias de vida. Para isto, doses sub-efetivas de 3-ASP (10 mg/kg; p.o.) e ácido DL-2,4-diamino-n-butírico hidroclorado (DABA - um inibidor da captação de GABA; 2 mg/kg; i.p.) ou ácido aminooxiacético hemihidroclorado (AOAA um inibidor da GABA-T; 10 mg/kg, i.p.) foram co-administrados em ratos de 21 dias de vida antes da administração de PC (400 mg/kg; i.p.). A presença de episódios convulsivos foi avaliada. Verificamos que o tratamento com o 3-ASP e DABA aboliu as convulsões induzidas por PC, corroborando com nossos resultados neuroquímicos. O mesmo foi observado quando foram administradas doses sub-efetivas de 3-ASP e AOAA. Por fim, no artigo 3 investigamos o efeito do 3-ASP ou diazepam frente as convulsões, aumento da susceptibilidade ao desenvolvimento de convulsões e prejuízo na memória a longo prazo resultantes da convulsão febril induzida pela hipertermia. Os ratos de 21 dias de vida foram pré-tratados com 3-ASP (25, 50 ou 100 mg/kg; p.o), diazepam (1 ou 5 mg/kg; i.p.) ou veículo. Após o pré-tratamento, os animais foram expostos a uma temperatura de 41°C. Trinta dias após a exposição à hipertermia, avaliamos o aumento da susceptibilidade ao desenvolvimento de convulsões e prejuízo na memória a longo prazo. Verificamos que o pré-tratamento com 3-ASP ou diazepam não foi capaz de proteger contra o comportamento estereotipado, automatismos faciais e flexão corporal induzidos pela hipertermia. O efeito protetor do 3-ASP (100 mg/kg) contra o aumento da susceptibilidade ao desenvolvimento de convulsões e prejuízo na memória a longo prazo resultantes da convulsão febril induzida pela hipertermia foi verificado. O diazepam (1 ou 5 mg/kg) não protegeu contra o prejuízo na memória a longo prazo causado pela convulsão febril. Além disso, o tratamento com diazepam (1 mg/kg) nos animais mantidos a temperatura ambiente causou um significativo prejuízo cognitivo. Estes resultados sugerem que o 3-ASP apresenta ação anticonvulsivante em ratos de 21 dias de vida e que essa ação parece ser mediada pelos sistemas glutamatérgico e GABAérgico. Além disso, a ação anticonvulsivante do 3-ASP parece estar associada à sua atividade antioxidante. Por fim, o 3-ASP pode representar uma importante ferramenta para a proteção contra o aumento à susceptibilidade às convulsões e o prejuízo cognitivo resultantes das convulsões febris.Universidade Federal de Santa MariaBRBioquímicaUFSMPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaNogueira, Cristina Waynehttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4728219Y9Furian, Ana Fláviahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4705849T6Mazzanti, Cinthia Melazzo Andradehttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4776635P4Emanuelli, Tatianahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4797080Z5Soares, Félix Alexandre Antuneshttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4769181A8Wilhelm, Ethel Antunes2012-11-192012-11-192012-03-02info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfapplication/pdfWILHELM, Ethel Antunes. PHARMACOLOGICAL ACTION OF 3-ALKYNYL SELENOPHENE ON MODELS OF SEIZURES IN RAT PUPS. 2012. 104 f. Tese (Doutorado em Ciências Biológicas) - Universidade Federal de Santa Maria, Santa Maria, 2012.http://repositorio.ufsm.br/handle/1/4453ark:/26339/0013000015v54porinfo:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2017-07-30T03:56:35Zoai:repositorio.ufsm.br:1/4453Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2017-07-30T03:56:35Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false
dc.title.none.fl_str_mv Ação farmacológica do 3-alquinil selenofeno em modelos de convulsão em ratos jovens
Pharmacological action of 3-alkynyl selenophene on models of seizures in rat pups
title Ação farmacológica do 3-alquinil selenofeno em modelos de convulsão em ratos jovens
spellingShingle Ação farmacológica do 3-alquinil selenofeno em modelos de convulsão em ratos jovens
Wilhelm, Ethel Antunes
3-alquinil selenofeno
Selênio
Anticonvulsivante
Hipertermia
Estresse oxidativo
Ácido γ-aminobutírico
Glutamato
3-alkynyl selenophene
Selenium
Anticonvulsant
Hiperthermia
Oxidative stress
γ-aminobutyric acid
Glutamate
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
title_short Ação farmacológica do 3-alquinil selenofeno em modelos de convulsão em ratos jovens
title_full Ação farmacológica do 3-alquinil selenofeno em modelos de convulsão em ratos jovens
title_fullStr Ação farmacológica do 3-alquinil selenofeno em modelos de convulsão em ratos jovens
title_full_unstemmed Ação farmacológica do 3-alquinil selenofeno em modelos de convulsão em ratos jovens
title_sort Ação farmacológica do 3-alquinil selenofeno em modelos de convulsão em ratos jovens
author Wilhelm, Ethel Antunes
author_facet Wilhelm, Ethel Antunes
author_role author
dc.contributor.none.fl_str_mv Nogueira, Cristina Wayne
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4728219Y9
Furian, Ana Flávia
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4705849T6
Mazzanti, Cinthia Melazzo Andrade
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4776635P4
Emanuelli, Tatiana
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4797080Z5
Soares, Félix Alexandre Antunes
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4769181A8
dc.contributor.author.fl_str_mv Wilhelm, Ethel Antunes
dc.subject.por.fl_str_mv 3-alquinil selenofeno
Selênio
Anticonvulsivante
Hipertermia
Estresse oxidativo
Ácido γ-aminobutírico
Glutamato
3-alkynyl selenophene
Selenium
Anticonvulsant
Hiperthermia
Oxidative stress
γ-aminobutyric acid
Glutamate
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
topic 3-alquinil selenofeno
Selênio
Anticonvulsivante
Hipertermia
Estresse oxidativo
Ácido γ-aminobutírico
Glutamato
3-alkynyl selenophene
Selenium
Anticonvulsant
Hiperthermia
Oxidative stress
γ-aminobutyric acid
Glutamate
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
description Seizures have important consequences in terms of mortality and quality of life of the affected population, being a risk factor for the development of cognitive and behavioral abnormalities. Considering the promising pharmacological properties of molecules containing selenium, in article 1, we evaluated the anticonvulsant action of 1-(2,5-diphenylselenophen-3-yl)-3-methylpent-1-yn-3-ol, generically called 3-alkynyl selenophene (3-ASP) against seizures induced by pilocarpine (PC), pentylenetetrazole (PTZ) and kainate (KA) in 21-days-old rats. Animals were pre-treated with 3-ASP (10, 25 or 50 mg/kg; per oral, p.o.) or vehicle, 30 minutes before of intraperitoneally administration of PC (400 mg/kg), PTZ (80 mg/kg) or KA (45 mg/kg). 3-ASP pre-treatment (50 mg/kg) abolished seizures and the death induced by PC administration. 3-ASP (50 mg/kg) increased the latency to the first convulsive episode, as well as decreased the mortality and incidence of seizures caused by PTZ and KA. In article 1, the antioxidant activity of 3-ASP (10, 25 or 50 mg/kg; p.o.) against the oxidative stress induced by PC (400 mg/kg, i.p.) in 21-days-old rats was evaluated. Our results demonstrated that 3-ASP pre-treatment was effective in protecting against the inhibition of cerebral activity of superoxide dismutase, decreased ascorbic acid levels, stimulation of catalase activity and increase of reactive species levels caused by PC. Additionally, 3-ASP protected against the inhibition of acetylcholinesterase and Na+, K+-ATPase activities resulting from convulsions induced by PC. The involvement of glutamatergic and GABAergic systems in the anticonvulsant action of 3-ASP was investigated (Articles 1 and 2). The combination of sub-effective doses of 3-ASP (10 mg/kg, p.o.) and diazepam (GABA agonist; 0,5 mg/kg, i.p.), 5S,10R-(+)-5-methyl-10,11-dihydro- 5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist; 0.1mg/kg, i.p.) or 6,7-dinitroquinoxaline-2,3-dione (DNQX, a non-NMDA receptor antagonist; 5 mg/kg, i.p.) was effective in increasing the latency to the first convulsive episode, as well as, in decreasing the incidence of convulsions induced by PC. On the other hand, the combination of 3-ASP and 2-methyl-6-phenylethynyl pyridine hydrochloride (MPEP, an antagonist of metabotropic glutamate receptor mGluR5; 0,5 mg/kg, i.p.) did not protect against convulsions. The oral administration of 3-ASP (50 mg/kg) caused an inhibition of 64% and 58% of GABA uptake in the cortex and hippocampus, respectively. However, no change in glutamate uptake after 3-ASP administration (50 mg/kg) was found. Additionally, in article 2, we investigated the possible interaction between sub-effective doses of 3-ASP and GABA uptake or GABA transaminase (GABA-T) inhibitors against PC-induced seizures in 21-days-old rats. To this, sub-effective doses of 3-ASP (10 mg/kg; p.o.) and DL-2,4-diamino-n-butyric acid hydrochloride (DABA, an inhibitor of GABA uptake; 2 mg/kg; i.p.) or aminooxyacetic acid hemihydrochloride (AOAA; a GABA-T inhibitor; 10 mg/kg, i.p.) were co-administrated in 21-days-old rats before of PC administration (400 mg/kg). The treatment with 3-ASP and DABA abolished the PC-induced seizures. Similar results were found when sub-effective doses of 3-ASP and AOAA were administrated in 21-days-old rats. Finally, in the article 3 we investigated the effect of 3-ASP or diazepam against convulsions, the increased susceptibility to the development of seizures and long term memory impairment resulting from febrile seizures induced by hyperthermia. 21-Days-old rats were pre-treated with 3-ASP (25, 50 or 100 mg/kg; p.o), diazepam (1 or 5 mg/kg; i.p.) or vehicle. After the treatment, animals were exposed to a stream of heated air to approximately 41°C. Thirty days after the exposure to hyperthermia, the susceptibility to the development of seizures and long term memory impairment were evaluated. We verified that the pre-treatment with 3-ASP or diazepam did not protect against stereotyped behavior, facial automatisms and body flexion induced by hyperthermia. The protective effect of 3-ASP (100 mg/kg) against the increased susceptibility to the development of seizures and long term memory impairment resulting from febrile seizures induced by hyperthermia was demonstrated. Diazepam (1 or 5 mg/kg) did not protect against long term memory impairment caused by febrile seizures. In addition, diazepam (1 mg/kg) treatment caused a significant cognitive impairment in animals kept at room temperature. These results suggest that 3-ASP had anticonvulsant action in 21-days-old rats and that this action appears to be mediated by glutamatergic and GABAergic systems. In addition, the anticonvulsant action of 3-ASP seems to be associated with its antioxidant activity. Finally, 3-ASP can represent an important tool to protect against increased susceptibility to seizures and cognitive impairment resulting from febrile seizures.
publishDate 2012
dc.date.none.fl_str_mv 2012-11-19
2012-11-19
2012-03-02
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv WILHELM, Ethel Antunes. PHARMACOLOGICAL ACTION OF 3-ALKYNYL SELENOPHENE ON MODELS OF SEIZURES IN RAT PUPS. 2012. 104 f. Tese (Doutorado em Ciências Biológicas) - Universidade Federal de Santa Maria, Santa Maria, 2012.
http://repositorio.ufsm.br/handle/1/4453
dc.identifier.dark.fl_str_mv ark:/26339/0013000015v54
identifier_str_mv WILHELM, Ethel Antunes. PHARMACOLOGICAL ACTION OF 3-ALKYNYL SELENOPHENE ON MODELS OF SEIZURES IN RAT PUPS. 2012. 104 f. Tese (Doutorado em Ciências Biológicas) - Universidade Federal de Santa Maria, Santa Maria, 2012.
ark:/26339/0013000015v54
url http://repositorio.ufsm.br/handle/1/4453
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Universidade Federal de Santa Maria
BR
Bioquímica
UFSM
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica
publisher.none.fl_str_mv Universidade Federal de Santa Maria
BR
Bioquímica
UFSM
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica
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
_version_ 1815172455187087360