Associação entre o consumo de antocianinas e a prevenção de alterações cognitivas, neuroquímicas e inflamatórias nos modelos experimentais de desmielinização e de neuroinflamação em roedores
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/17573 |
Resumo: | Anthocyanins (ANT) are phytonutrients with antioxidant and neuroprotective properties. In this context, this study sought evidence of a possible protective effect of ANT on models of demyelination and neuroinflammation in rodents. Rats were submitted to the experimental demyelination by ethidium bromide injection (EB, 0.1% in saline, 10 μL) in the pons. In addition, an in vitro experiment was conducted to check whether ANT (1-100 μg/mL) are able to reduce the oxidative and nitrosative stress in pons of rats exposed to hydrogen peroxide (H2O2, 4 mM) and sodium nitroprusside (NPS, 1 mM). C57BL6 mice were subjected to neuroinflammation by acute administration lipopolysaccharide (LPS 250 μg/kg, 5 mL/kg, in saline) intraperitoneally. ANT doses in both protocols were 30 and 100 mg/kg (via oral by gavage, vehicle saline). The ANT were able to neutralize the reactive species induced by H2O2 and by NPS reducing the malondialdehyde, protein carbonyl and nitrites and nitrates (NOx) contents. In relation to the model of toxic demyelination, ANT obtained from grape skins were administered during 7 days from the BE injection. On the seventh day the animals were euthanized. It can be seen a protective effect of ANT on the increase in oxidative stress markers: malondialdehyde, carbonyl protein and NOx levels. ANT also protected the reduction in superoxide dismutase activity and the NPSH / GSH content. A negative correlation showed an increase in markers of oxidative stress and the reduction in activity of the enzymes Na+, K+-ATPase and Ca2+-ATPase. ANT restored the activity of ions pumps. In parallel, ANT reduced the increase in interleukin (IL)-1β, IL-6, tumoral necrosis factor (TNF)-α and interferon (INF)-γ induced by the EB. ANT suppressed the local inflammatory infiltrate, the presence of neutrophils and reduced demyelination area. In relation to neuroinflammation model, the pretreatment ten days with ANT from blueberry prevented the memory loss induced by LPS administered post-training. ANT also prevented the increased in the malondialdehyde, carbonyl protein and NOx levels 4 and 24 hours post-LPS administration in the cerebral cortex and hippocampus. ANT not prevented the reduction in the Na+, K+-ATPase activity but were able to suppress the neutrophil infiltration and microglial immunoreactivity in the hippocampus 24 hours after LPS administration. The neuroinflammation and demyelination were not able to induce significant neuronal death but alter the morphology of these cells. ANT were able to prevent this effect. These results suggest that ANT can act as adjuvants in the treatment of diseases characterized by neuroinflammation and demyelination episodes, among them stands out Multiple Sclerosis. |
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Associação entre o consumo de antocianinas e a prevenção de alterações cognitivas, neuroquímicas e inflamatórias nos modelos experimentais de desmielinização e de neuroinflamação em roedoresAssociation between anthocyanins consumption and prevention of cognitive, neurochemical and inflammatory alterations in experimental models of demyelination and neuroinflammation in rodentsDesmielinizaçãoNeuroinflamaçãoAntocianinasBombas iônicasEstresse oxidativoRoedoresDemyelinationNeuroinflammationAnthocyaninsIonic pumpsOxidative stressRodentsCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAAnthocyanins (ANT) are phytonutrients with antioxidant and neuroprotective properties. In this context, this study sought evidence of a possible protective effect of ANT on models of demyelination and neuroinflammation in rodents. Rats were submitted to the experimental demyelination by ethidium bromide injection (EB, 0.1% in saline, 10 μL) in the pons. In addition, an in vitro experiment was conducted to check whether ANT (1-100 μg/mL) are able to reduce the oxidative and nitrosative stress in pons of rats exposed to hydrogen peroxide (H2O2, 4 mM) and sodium nitroprusside (NPS, 1 mM). C57BL6 mice were subjected to neuroinflammation by acute administration lipopolysaccharide (LPS 250 μg/kg, 5 mL/kg, in saline) intraperitoneally. ANT doses in both protocols were 30 and 100 mg/kg (via oral by gavage, vehicle saline). The ANT were able to neutralize the reactive species induced by H2O2 and by NPS reducing the malondialdehyde, protein carbonyl and nitrites and nitrates (NOx) contents. In relation to the model of toxic demyelination, ANT obtained from grape skins were administered during 7 days from the BE injection. On the seventh day the animals were euthanized. It can be seen a protective effect of ANT on the increase in oxidative stress markers: malondialdehyde, carbonyl protein and NOx levels. ANT also protected the reduction in superoxide dismutase activity and the NPSH / GSH content. A negative correlation showed an increase in markers of oxidative stress and the reduction in activity of the enzymes Na+, K+-ATPase and Ca2+-ATPase. ANT restored the activity of ions pumps. In parallel, ANT reduced the increase in interleukin (IL)-1β, IL-6, tumoral necrosis factor (TNF)-α and interferon (INF)-γ induced by the EB. ANT suppressed the local inflammatory infiltrate, the presence of neutrophils and reduced demyelination area. In relation to neuroinflammation model, the pretreatment ten days with ANT from blueberry prevented the memory loss induced by LPS administered post-training. ANT also prevented the increased in the malondialdehyde, carbonyl protein and NOx levels 4 and 24 hours post-LPS administration in the cerebral cortex and hippocampus. ANT not prevented the reduction in the Na+, K+-ATPase activity but were able to suppress the neutrophil infiltration and microglial immunoreactivity in the hippocampus 24 hours after LPS administration. The neuroinflammation and demyelination were not able to induce significant neuronal death but alter the morphology of these cells. ANT were able to prevent this effect. These results suggest that ANT can act as adjuvants in the treatment of diseases characterized by neuroinflammation and demyelination episodes, among them stands out Multiple Sclerosis.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESAs antocianinas (ANT) são fitonutrientes com propriedades antioxidantes e neuroprotetoras. Neste contexto, este estudo buscou evidências de um possível efeito protetor das ANT em modelos de neuroinflamação e desmielinização em roedores. Ratos foram submetidos a desmielinização experimental pela administração de brometo de etídio (BE, 0,1% em salina, 10 μL) intra-pontine. Além disso um experimento in vitro foi conduzido para verificar se as ANT (1-100 μg/mL) são capazes de reduzir o estresse oxidativo e nitrosativo na ponte de ratos expostos a peróxido de hidrogênio (H2O2, 4 mM) e nitroprussiato de sódio (NPS, 1 mM). Camundongos C57BL6 foram submetidos a neuroinflamação pela administração aguda de lipopolissacarídeo (LPS 250 μg/kg, 5 mL/kg, em salina) intraperitonealmente. As doses de ANT para ambos os protocolos foram de 30 e 100 mg/kg (via oral, gavagem, em salina). As ANT foram capazes de neutralizar as espécies reativas induzidas pelo H2O2 e pelo NPS reduzindo o conteúdo de malondialdeído, proteína carbonil e nitritos e nitratos (NOx). Em relação ao modelo de desmielinização tóxica, as ANT provenientes da casca da uva foram administradas durante 7 dias a partir da injeção de BE. No sétimo dia os animais foram submetidos a eutanásia. Pode-se observar um efeito protetor das ANT sobre o aumento nos marcadores de estresse oxidativo: malondialdeído, proteína carbonil e NOx. ANT protegeram também a redução na atividade da enzima superóxido dismutase e no conteúdo de tióis não proteícos e glutationa reduzida. Uma correlação negativa mostrou um aumento nos marcadores de estresse oxidativo e uma redução na atividade das enzimas Na+,K+-ATPase e Ca2+-ATPase. As ANT restabeleceram a atividade das bombas iônicas. As ANT também reduziram o aumento de interleucinas (IL)-1β, IL-6, fator de necrose tumoral (TNF)-α e interferon (INF)-γ induzidos pelo BE. As ANT suprimiram o infiltrado inflamatório local, a presença de neutrófilos e reduziram a área de desmielinização. Em relação ao modelo de neuroinflamação, o pré-tratamento durante dez dias com ANT provenientes do mirtilo preveniram a piora na memória induzido pelo LPS administrado pós-treino. ANT preveniram também o aumento do conteúdo de malondialdeído, proteína carbonil e NOx no córtex cerebral e no hipocampo 4 e 24 horas pós-administração de LPS. ANT não mostraram efeito protetor sobre a redução na atividade da enzima Na+,K+-ATPase, mas foram capazes de suprimir o processo inflamatório e a presença de neutrófilos, bem como a imunoreatividade microglial para CD11b no hipocampo 24 horas pós administração de LPS. A desmielinização e a neuroinflamação não foram capazes de induzir morte significativa de neurônios da ponte e do hipocampo, mas sim alterar a morfologia destas células. ANT foram capazes de prevenir este efeito. Estes resultados sugerem que as ANT podem atuar como coadjuvantes no tratamento de doenças caraterizadas por episódios de neuroinflamação e desmielinização, dentre estas se destaca a Esclerose Múltipla.Universidade Federal de Santa MariaBrasilBioquímicaUFSMPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaCentro de Ciências Naturais e ExatasAndrade, Cinthia Melazzo dehttp://lattes.cnpq.br/2886709251370905Gutierres, Jessié Martinshttp://lattes.cnpq.br/8202862581642039Morsch, Vera Maria Melchiorshttp://lattes.cnpq.br/1519648219507868Cruz, Ivana Beatrice Mânica Dahttp://lattes.cnpq.br/3426369324110716Stefanello, Francieli Morohttp://lattes.cnpq.br/8828875564145245Ghisleni, Gabriele Cordenonzihttp://lattes.cnpq.br/3918025526443507Carvalho, Fabiano Barbosa2019-07-26T21:55:05Z2019-07-26T21:55:05Z2015-08-14info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/17573porAttribution-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:UFSM2019-07-27T06:02:13Zoai:repositorio.ufsm.br:1/17573Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2019-07-27T06:02:13Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Associação entre o consumo de antocianinas e a prevenção de alterações cognitivas, neuroquímicas e inflamatórias nos modelos experimentais de desmielinização e de neuroinflamação em roedores Association between anthocyanins consumption and prevention of cognitive, neurochemical and inflammatory alterations in experimental models of demyelination and neuroinflammation in rodents |
title |
Associação entre o consumo de antocianinas e a prevenção de alterações cognitivas, neuroquímicas e inflamatórias nos modelos experimentais de desmielinização e de neuroinflamação em roedores |
spellingShingle |
Associação entre o consumo de antocianinas e a prevenção de alterações cognitivas, neuroquímicas e inflamatórias nos modelos experimentais de desmielinização e de neuroinflamação em roedores Carvalho, Fabiano Barbosa Desmielinização Neuroinflamação Antocianinas Bombas iônicas Estresse oxidativo Roedores Demyelination Neuroinflammation Anthocyanins Ionic pumps Oxidative stress Rodents CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Associação entre o consumo de antocianinas e a prevenção de alterações cognitivas, neuroquímicas e inflamatórias nos modelos experimentais de desmielinização e de neuroinflamação em roedores |
title_full |
Associação entre o consumo de antocianinas e a prevenção de alterações cognitivas, neuroquímicas e inflamatórias nos modelos experimentais de desmielinização e de neuroinflamação em roedores |
title_fullStr |
Associação entre o consumo de antocianinas e a prevenção de alterações cognitivas, neuroquímicas e inflamatórias nos modelos experimentais de desmielinização e de neuroinflamação em roedores |
title_full_unstemmed |
Associação entre o consumo de antocianinas e a prevenção de alterações cognitivas, neuroquímicas e inflamatórias nos modelos experimentais de desmielinização e de neuroinflamação em roedores |
title_sort |
Associação entre o consumo de antocianinas e a prevenção de alterações cognitivas, neuroquímicas e inflamatórias nos modelos experimentais de desmielinização e de neuroinflamação em roedores |
author |
Carvalho, Fabiano Barbosa |
author_facet |
Carvalho, Fabiano Barbosa |
author_role |
author |
dc.contributor.none.fl_str_mv |
Andrade, Cinthia Melazzo de http://lattes.cnpq.br/2886709251370905 Gutierres, Jessié Martins http://lattes.cnpq.br/8202862581642039 Morsch, Vera Maria Melchiors http://lattes.cnpq.br/1519648219507868 Cruz, Ivana Beatrice Mânica Da http://lattes.cnpq.br/3426369324110716 Stefanello, Francieli Moro http://lattes.cnpq.br/8828875564145245 Ghisleni, Gabriele Cordenonzi http://lattes.cnpq.br/3918025526443507 |
dc.contributor.author.fl_str_mv |
Carvalho, Fabiano Barbosa |
dc.subject.por.fl_str_mv |
Desmielinização Neuroinflamação Antocianinas Bombas iônicas Estresse oxidativo Roedores Demyelination Neuroinflammation Anthocyanins Ionic pumps Oxidative stress Rodents CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
topic |
Desmielinização Neuroinflamação Antocianinas Bombas iônicas Estresse oxidativo Roedores Demyelination Neuroinflammation Anthocyanins Ionic pumps Oxidative stress Rodents CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Anthocyanins (ANT) are phytonutrients with antioxidant and neuroprotective properties. In this context, this study sought evidence of a possible protective effect of ANT on models of demyelination and neuroinflammation in rodents. Rats were submitted to the experimental demyelination by ethidium bromide injection (EB, 0.1% in saline, 10 μL) in the pons. In addition, an in vitro experiment was conducted to check whether ANT (1-100 μg/mL) are able to reduce the oxidative and nitrosative stress in pons of rats exposed to hydrogen peroxide (H2O2, 4 mM) and sodium nitroprusside (NPS, 1 mM). C57BL6 mice were subjected to neuroinflammation by acute administration lipopolysaccharide (LPS 250 μg/kg, 5 mL/kg, in saline) intraperitoneally. ANT doses in both protocols were 30 and 100 mg/kg (via oral by gavage, vehicle saline). The ANT were able to neutralize the reactive species induced by H2O2 and by NPS reducing the malondialdehyde, protein carbonyl and nitrites and nitrates (NOx) contents. In relation to the model of toxic demyelination, ANT obtained from grape skins were administered during 7 days from the BE injection. On the seventh day the animals were euthanized. It can be seen a protective effect of ANT on the increase in oxidative stress markers: malondialdehyde, carbonyl protein and NOx levels. ANT also protected the reduction in superoxide dismutase activity and the NPSH / GSH content. A negative correlation showed an increase in markers of oxidative stress and the reduction in activity of the enzymes Na+, K+-ATPase and Ca2+-ATPase. ANT restored the activity of ions pumps. In parallel, ANT reduced the increase in interleukin (IL)-1β, IL-6, tumoral necrosis factor (TNF)-α and interferon (INF)-γ induced by the EB. ANT suppressed the local inflammatory infiltrate, the presence of neutrophils and reduced demyelination area. In relation to neuroinflammation model, the pretreatment ten days with ANT from blueberry prevented the memory loss induced by LPS administered post-training. ANT also prevented the increased in the malondialdehyde, carbonyl protein and NOx levels 4 and 24 hours post-LPS administration in the cerebral cortex and hippocampus. ANT not prevented the reduction in the Na+, K+-ATPase activity but were able to suppress the neutrophil infiltration and microglial immunoreactivity in the hippocampus 24 hours after LPS administration. The neuroinflammation and demyelination were not able to induce significant neuronal death but alter the morphology of these cells. ANT were able to prevent this effect. These results suggest that ANT can act as adjuvants in the treatment of diseases characterized by neuroinflammation and demyelination episodes, among them stands out Multiple Sclerosis. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-08-14 2019-07-26T21:55:05Z 2019-07-26T21:55:05Z |
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 |
http://repositorio.ufsm.br/handle/1/17573 |
url |
http://repositorio.ufsm.br/handle/1/17573 |
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 Bioquímica UFSM Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica Centro de Ciências Naturais e Exatas |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Bioquímica UFSM Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica Centro de Ciências Naturais e Exatas |
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_ |
1805922046402625536 |