Efeito da exposição aguda à fumonisina B1 nas convulsões induzidas por pentilenotetrazol em camundongos
Ano de defesa: | 2014 |
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Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | |
Tipo de documento: | Dissertação |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Santa Maria
BR Farmacologia UFSM Programa de Pós-Graduação em Farmacologia |
Programa de Pós-Graduação: |
Não Informado pela instituição
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Departamento: |
Não Informado pela instituição
|
País: |
Não Informado pela instituição
|
Palavras-chave em Português: | |
Link de acesso: | http://repositorio.ufsm.br/handle/1/9034 |
Resumo: | Mycotoxins are secondary metabolites, produced by fungi species of the genus Aspergillus, Fusarium, Penicillium and Claviceps. The high incidence of toxicity is by ingestion of contaminated plant products and by consuming products derived from food. Among the 400 different mycotoxins; there are the fumonisins, especially fumonisin B1 (FB1), which corresponds to about 70% of total fumonisins. It has been demonstrated that toxicity of this mycotoxin may be related to toxic effects on the central nervous system, engaging in inflammatory processes and seizures. The mechanism of toxicity of fumonisins is related to the metabolism of sphingolipids in which the breakdown of these sphingolipids complexes and accumulation of sphingoid bases alter important cellular functions, favoring oxidative stress, inhibition of protein secondary and excitotoxicity. Thus, this work tried to investigate whether FB1 is able to enhance the inductive effect of the model of pentylenetetrazole (PTZ) seizures. We also evaluated the mechanism of action responsible for this effect, in order to study strategies that make it possible to prevent or minimize their toxic effects. So, C57BL/6 mice were exposed to FB1 (8 mg/kg i.p.) or vehicle (1.6% DMSO + 0.9% NaCl i.p.) and elapsed 30 minutes were injected with PTZ (30 mg/kg i.p.) or vehicle (0,9% NaCl i.p.). Behind 15 minutes observation, mice were euthanized and cerebral cortex and hippocampus were collected for analysis of Na+, K+-ATPase activity, membrane potential and mitochondrial complex I and II activities. FB1 reduced latency for myoclonic jerks and increased myoclonus number. Even, Na+, K+-ATPase total activity as well as subunit �1of this enzyme were increased in cerebral cortex of animals treated with FB1, but in hippocampus it was reduced. FB1 elevated mitochondrial membrane potential in cerebral cortex however mitochondrial complex I and II activity weren t changed in both structures with this treatment. PTZ was able to enhance Na+, K+-ATPase �2/�3 subunit activity in hippocampus. Thus, we showed that FB1 induces neurotoxicity, since this mycotoxin FB1 facilitates seizures induced by PTZ, altered mitochondrial membrane potential and the enzyme Na+, K+ - ATPase activity, which are possibly mediating the mechanism of toxicity. |
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Efeito da exposição aguda à fumonisina B1 nas convulsões induzidas por pentilenotetrazol em camundongosEffect of acute exposition to fumonisin B1 in the seizure induced by pentylenetetrazole in miceMicotoxinasPotencial de membrana mitocondrialNa+, K+ ATPaseSistema nervoso centralMycotoxinsMitochondrial membrane potentialNa+K+ ATPaseCentral nervous sistemCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIAMycotoxins are secondary metabolites, produced by fungi species of the genus Aspergillus, Fusarium, Penicillium and Claviceps. The high incidence of toxicity is by ingestion of contaminated plant products and by consuming products derived from food. Among the 400 different mycotoxins; there are the fumonisins, especially fumonisin B1 (FB1), which corresponds to about 70% of total fumonisins. It has been demonstrated that toxicity of this mycotoxin may be related to toxic effects on the central nervous system, engaging in inflammatory processes and seizures. The mechanism of toxicity of fumonisins is related to the metabolism of sphingolipids in which the breakdown of these sphingolipids complexes and accumulation of sphingoid bases alter important cellular functions, favoring oxidative stress, inhibition of protein secondary and excitotoxicity. Thus, this work tried to investigate whether FB1 is able to enhance the inductive effect of the model of pentylenetetrazole (PTZ) seizures. We also evaluated the mechanism of action responsible for this effect, in order to study strategies that make it possible to prevent or minimize their toxic effects. So, C57BL/6 mice were exposed to FB1 (8 mg/kg i.p.) or vehicle (1.6% DMSO + 0.9% NaCl i.p.) and elapsed 30 minutes were injected with PTZ (30 mg/kg i.p.) or vehicle (0,9% NaCl i.p.). Behind 15 minutes observation, mice were euthanized and cerebral cortex and hippocampus were collected for analysis of Na+, K+-ATPase activity, membrane potential and mitochondrial complex I and II activities. FB1 reduced latency for myoclonic jerks and increased myoclonus number. Even, Na+, K+-ATPase total activity as well as subunit �1of this enzyme were increased in cerebral cortex of animals treated with FB1, but in hippocampus it was reduced. FB1 elevated mitochondrial membrane potential in cerebral cortex however mitochondrial complex I and II activity weren t changed in both structures with this treatment. PTZ was able to enhance Na+, K+-ATPase �2/�3 subunit activity in hippocampus. Thus, we showed that FB1 induces neurotoxicity, since this mycotoxin FB1 facilitates seizures induced by PTZ, altered mitochondrial membrane potential and the enzyme Na+, K+ - ATPase activity, which are possibly mediating the mechanism of toxicity.Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorAs micotoxinas são metabólitos secundários, produzidas por espécies de fungos dos gêneros Aspergillus, Fusarium, Claviceps e Penicillium. Geralmente as intoxicações se dão pela ingestão de produtos vegetais contaminados, bem como pelo consumo de alimentos derivados. Dentre os 400 diferentes tipos de micotoxinas, destacam-se as fumonisinas, em especial a fumonisina B1 (FB1) que corresponde a cerca de 70% das fumonisinas totais. Tem sido demonstrado que a toxicidade desta micotoxina pode estar relacionada com efeitos tóxicos no sistema nervoso central, envolvendo-se em processos inflamatórios e crises convulsivas. O mecanismo de toxicidade das fumonisinas está relacionado ao metabolismo dos esfingolipídios no qual o esgotamento desses esfingolipídios complexos e o acúmulo das bases esfingóides alteram funções celulares importantes, favorecendo estresse oxidativo, a inibição secundária de proteínas e excitotoxicidade. Deste modo, este estudo investigou se a FB1 é capaz de facilitar o efeito indutor de convulsões do modelo do pentilenotetrazol (PTZ). Avaliamos também o mecanismo de ação responsável por tal efeito, a fim de estudar estratégias que tornem possível a prevenção ou minimização dos seus efeitos tóxicos. Assim, camundongos machos C57BL/6 foram expostos a FB1 (8 mg/kg i.p.) ou veículo (1,6% DMSO + 0,9% NaCl i.p.) e após 30 minutos injetados com PTZ (30 mg/kg i.p.) ou veículo (0,9% NaCl i.p.). Após 15 minutos de observação, os camundongos foram eutanasiados e o córtex cerebral e o hipocampo foram coletados para a análise das enzimas Na+, K+-ATPase e o potencial de membrana mitocondrial e as atividades dos complexos I e II mitocondriais. A FB1 reduziu a latência para mioclonias e aumentou o número de mioclonias. Da mesma forma, a atividade total e da subunidade �1 da Na+, K+-ATPase foi aumentada no córtex cerebral de animais tratados com FB1, mas no hipocampo foi reduzida. A FB1 elevou o potencial de membrana mitocondrial no córtex cerebral, porém a atividade dos complexos I e II da cadeia respiratória não foram alteradas em ambas estruturas com este tratamento. O PTZ foi capaz de aumentar a subunidade �2/�3 da Na+, K+-ATPase no hipocampo. Assim, mostramos que a FB1 induz a neurotoxidade, pois esta micotoxina facilitou as convulsões induzidas por PTZ, alterou o potencial de membrana mitocondrial e a atividade da enzima Na+, K+-ATPase, que possivelmente estão mediando o mecanismo da toxicidade.Universidade Federal de Santa MariaBRFarmacologiaUFSMPrograma de Pós-Graduação em FarmacologiaFurian, Ana Fláviahttp://lattes.cnpq.br/0865191340133424Burger, Marilise Escobarhttp://lattes.cnpq.br/9128090974948413Oliveira, Sara Marchesan dehttp://lattes.cnpq.br/6574555059806902Ferreira, Ana Paula de Oliveirahttp://lattes.cnpq.br/3053349368036300Poersch, Alice Bertotto2016-12-142016-12-142014-07-24info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfapplication/pdfPOERSCH, Alice Bertotto. Effect of acute exposition to fumonisin B1 in the seizure induced by pentylenetetrazole in mice. 2014. 65 f. Dissertação (Mestrado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2014.http://repositorio.ufsm.br/handle/1/9034porinfo:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2022-01-10T12:12:07Zoai:repositorio.ufsm.br:1/9034Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2022-01-10T12:12:07Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Efeito da exposição aguda à fumonisina B1 nas convulsões induzidas por pentilenotetrazol em camundongos Effect of acute exposition to fumonisin B1 in the seizure induced by pentylenetetrazole in mice |
title |
Efeito da exposição aguda à fumonisina B1 nas convulsões induzidas por pentilenotetrazol em camundongos |
spellingShingle |
Efeito da exposição aguda à fumonisina B1 nas convulsões induzidas por pentilenotetrazol em camundongos Poersch, Alice Bertotto Micotoxinas Potencial de membrana mitocondrial Na+, K+ ATPase Sistema nervoso central Mycotoxins Mitochondrial membrane potential Na+ K+ ATPase Central nervous sistem CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
title_short |
Efeito da exposição aguda à fumonisina B1 nas convulsões induzidas por pentilenotetrazol em camundongos |
title_full |
Efeito da exposição aguda à fumonisina B1 nas convulsões induzidas por pentilenotetrazol em camundongos |
title_fullStr |
Efeito da exposição aguda à fumonisina B1 nas convulsões induzidas por pentilenotetrazol em camundongos |
title_full_unstemmed |
Efeito da exposição aguda à fumonisina B1 nas convulsões induzidas por pentilenotetrazol em camundongos |
title_sort |
Efeito da exposição aguda à fumonisina B1 nas convulsões induzidas por pentilenotetrazol em camundongos |
author |
Poersch, Alice Bertotto |
author_facet |
Poersch, Alice Bertotto |
author_role |
author |
dc.contributor.none.fl_str_mv |
Furian, Ana Flávia http://lattes.cnpq.br/0865191340133424 Burger, Marilise Escobar http://lattes.cnpq.br/9128090974948413 Oliveira, Sara Marchesan de http://lattes.cnpq.br/6574555059806902 Ferreira, Ana Paula de Oliveira http://lattes.cnpq.br/3053349368036300 |
dc.contributor.author.fl_str_mv |
Poersch, Alice Bertotto |
dc.subject.por.fl_str_mv |
Micotoxinas Potencial de membrana mitocondrial Na+, K+ ATPase Sistema nervoso central Mycotoxins Mitochondrial membrane potential Na+ K+ ATPase Central nervous sistem CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
topic |
Micotoxinas Potencial de membrana mitocondrial Na+, K+ ATPase Sistema nervoso central Mycotoxins Mitochondrial membrane potential Na+ K+ ATPase Central nervous sistem CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
description |
Mycotoxins are secondary metabolites, produced by fungi species of the genus Aspergillus, Fusarium, Penicillium and Claviceps. The high incidence of toxicity is by ingestion of contaminated plant products and by consuming products derived from food. Among the 400 different mycotoxins; there are the fumonisins, especially fumonisin B1 (FB1), which corresponds to about 70% of total fumonisins. It has been demonstrated that toxicity of this mycotoxin may be related to toxic effects on the central nervous system, engaging in inflammatory processes and seizures. The mechanism of toxicity of fumonisins is related to the metabolism of sphingolipids in which the breakdown of these sphingolipids complexes and accumulation of sphingoid bases alter important cellular functions, favoring oxidative stress, inhibition of protein secondary and excitotoxicity. Thus, this work tried to investigate whether FB1 is able to enhance the inductive effect of the model of pentylenetetrazole (PTZ) seizures. We also evaluated the mechanism of action responsible for this effect, in order to study strategies that make it possible to prevent or minimize their toxic effects. So, C57BL/6 mice were exposed to FB1 (8 mg/kg i.p.) or vehicle (1.6% DMSO + 0.9% NaCl i.p.) and elapsed 30 minutes were injected with PTZ (30 mg/kg i.p.) or vehicle (0,9% NaCl i.p.). Behind 15 minutes observation, mice were euthanized and cerebral cortex and hippocampus were collected for analysis of Na+, K+-ATPase activity, membrane potential and mitochondrial complex I and II activities. FB1 reduced latency for myoclonic jerks and increased myoclonus number. Even, Na+, K+-ATPase total activity as well as subunit �1of this enzyme were increased in cerebral cortex of animals treated with FB1, but in hippocampus it was reduced. FB1 elevated mitochondrial membrane potential in cerebral cortex however mitochondrial complex I and II activity weren t changed in both structures with this treatment. PTZ was able to enhance Na+, K+-ATPase �2/�3 subunit activity in hippocampus. Thus, we showed that FB1 induces neurotoxicity, since this mycotoxin FB1 facilitates seizures induced by PTZ, altered mitochondrial membrane potential and the enzyme Na+, K+ - ATPase activity, which are possibly mediating the mechanism of toxicity. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014-07-24 2016-12-14 2016-12-14 |
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 |
POERSCH, Alice Bertotto. Effect of acute exposition to fumonisin B1 in the seizure induced by pentylenetetrazole in mice. 2014. 65 f. Dissertação (Mestrado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2014. http://repositorio.ufsm.br/handle/1/9034 |
identifier_str_mv |
POERSCH, Alice Bertotto. Effect of acute exposition to fumonisin B1 in the seizure induced by pentylenetetrazole in mice. 2014. 65 f. Dissertação (Mestrado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2014. |
url |
http://repositorio.ufsm.br/handle/1/9034 |
dc.language.iso.fl_str_mv |
por |
language |
por |
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info:eu-repo/semantics/openAccess |
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openAccess |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria BR Farmacologia UFSM Programa de Pós-Graduação em Farmacologia |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria BR Farmacologia UFSM Programa de Pós-Graduação em Farmacologia |
dc.source.none.fl_str_mv |
reponame:Manancial - Repositório Digital da UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
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Universidade Federal de Santa Maria (UFSM) |
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UFSM |
institution |
UFSM |
reponame_str |
Manancial - Repositório Digital da UFSM |
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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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