Efeitos do resveratrol na sinalização purinérgica em camundongos expostos ao alumínio
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
dARK ID: | ark:/26339/001300000phrk |
Texto Completo: | http://repositorio.ufsm.br/handle/1/30406 |
Resumo: | Aluminum (Al) is a compound found in nature, and is widely used industrially, which means that humans are exposed to it daily. Due to its ability to cross the blood-brain barrier, it can accumulate in the brain in regions of the hippocampus and cortex, which is why it has been associated with neurodegeneration. Previous studies suggest that combined with citrate (CIT), its absorption and, therefore, its toxic effects are increased, favoring the emergence of pathologies such as Alzheimer's disease (AD). AD is a progressive neurodegenerative disorder that leads to gradual memory loss. The relationship between Al and purinergic neurotransmission is recent, which is why it is necessary to study alternative methods that can act to protect against possible pathological states. The use of natural substances with antioxidant properties has stood out, in this context, resveratrol (RSV) has a widely reported anti-inflammatory capacity, in addition to being a potent activator of the Sirtuin family, having been used as an antioxidant and neuroprotector when it comes to FROM THE. Its neuroprotection mechanism has not yet been fully elucidated, therefore, the study of purinergic and oxidant/antioxidant signaling becomes essential. In this study, 60 male Swiss mice were divided into 6 groups (Control, CIT, RSV, Al, Al+CIT and Al+RSV) and treated for 30 days, every 48 hours. Through behavioral analyzes (Open field test, Object recognition and Y maze), it was possible to identify the reduction of short and medium-term memory in Swiss mice intoxicated with Al, as well as the increase in anxiety in these mice. It was also possible to observe the protective effects of RSV against Al intoxication, both in reducing anxiety and improving memory in mice. Enzymatic analyzes (NTPDase, 5'-NT and ADA) showed the inflammatory activity triggered by Al, through increased ATP hydrolysis in the intoxicated group, while RSV had an anti-inflammatory effect, reducing the hydrolysis of this nucleotide. In the case of ADA, we also observed a positive modulation of the activity of this enzyme in the inflammatory mechanism triggered by Al, as well as the neuroprotection exerted by RSV. Western Blot analyzes (A1, A2A, P2X7, NRLP3 and BDNF) confirmed the involvement of Al in the inflammatory mechanisms related to AD pathology and the neuroprotection exerted by RSV in these receptors. With this study, we concluded that Al acts by triggering inflammatory processes in the body of mice, impairing memory and causing severe anxiogenic states, and RSV has the ability to remedy these damages caused by Al, acting as a neuroprotector, improving the memory of mice and reducing inflammatory activities. |
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Efeitos do resveratrol na sinalização purinérgica em camundongos expostos ao alumínioResveratrol study on purinergic signaling in mice exposed to aluminumAlumínioCitratoToxicidadeResveratrolDoença de AlzheimerNeurodegeneraçãoSistema purinérgicoSistema oxidativoAluminumCitrateToxicityAlzheimer's diseaseNeurodegenerationPurinergic systemOxidative systemCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAAluminum (Al) is a compound found in nature, and is widely used industrially, which means that humans are exposed to it daily. Due to its ability to cross the blood-brain barrier, it can accumulate in the brain in regions of the hippocampus and cortex, which is why it has been associated with neurodegeneration. Previous studies suggest that combined with citrate (CIT), its absorption and, therefore, its toxic effects are increased, favoring the emergence of pathologies such as Alzheimer's disease (AD). AD is a progressive neurodegenerative disorder that leads to gradual memory loss. The relationship between Al and purinergic neurotransmission is recent, which is why it is necessary to study alternative methods that can act to protect against possible pathological states. The use of natural substances with antioxidant properties has stood out, in this context, resveratrol (RSV) has a widely reported anti-inflammatory capacity, in addition to being a potent activator of the Sirtuin family, having been used as an antioxidant and neuroprotector when it comes to FROM THE. Its neuroprotection mechanism has not yet been fully elucidated, therefore, the study of purinergic and oxidant/antioxidant signaling becomes essential. In this study, 60 male Swiss mice were divided into 6 groups (Control, CIT, RSV, Al, Al+CIT and Al+RSV) and treated for 30 days, every 48 hours. Through behavioral analyzes (Open field test, Object recognition and Y maze), it was possible to identify the reduction of short and medium-term memory in Swiss mice intoxicated with Al, as well as the increase in anxiety in these mice. It was also possible to observe the protective effects of RSV against Al intoxication, both in reducing anxiety and improving memory in mice. Enzymatic analyzes (NTPDase, 5'-NT and ADA) showed the inflammatory activity triggered by Al, through increased ATP hydrolysis in the intoxicated group, while RSV had an anti-inflammatory effect, reducing the hydrolysis of this nucleotide. In the case of ADA, we also observed a positive modulation of the activity of this enzyme in the inflammatory mechanism triggered by Al, as well as the neuroprotection exerted by RSV. Western Blot analyzes (A1, A2A, P2X7, NRLP3 and BDNF) confirmed the involvement of Al in the inflammatory mechanisms related to AD pathology and the neuroprotection exerted by RSV in these receptors. With this study, we concluded that Al acts by triggering inflammatory processes in the body of mice, impairing memory and causing severe anxiogenic states, and RSV has the ability to remedy these damages caused by Al, acting as a neuroprotector, improving the memory of mice and reducing inflammatory activities.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESO alumínio (Al) é um composto encontrado na natureza, e é largamente utilizado a nível industrial, o que faz com que os seres humanos estejam diariamente expostos a ele. Devido a sua capacidade de atravessar a barreira hematoencefálica, ele pode se acumular no cérebro em regiões do hipocampo e córtex, por isso tem sido associado a neurodegeneração. Estudos anteriores sugerem que combinado com o citrato (CIT), sua absorção e, portanto, seus efeitos tóxicos são ampliados, favorecendo o surgimento de patologias como a doença de Alzheimer (DA). A DA é um transtorno neurodegenerativo progressivo, que leva a perda de memória gradual. A relação entre Al e neurotransmissão purinérgica é recente, por isso torna-se necessário o estudo de métodos alternativos que possam atuar protegendo contra possíveis estados patológicos. O uso de substâncias naturais com propriedades antioxidantes tem se destacado, nesse contexto, o resveratrol (RSV) tem capacidade anti-inflamatória amplamente relatada, além de ser um potente ativador da família das Sirtuinas, tendo sido utilizado como antioxidante e neuroprotetor quando se trata da DA. Seu mecanismo de neuroproteção ainda não foi totalmente elucidado, dessa maneira, o estudo das sinalizações purinérgicas e oxidantes/antioxidantes torna-se essencial. Nesse estudo, 60 camundongos swiss machos foram divididos em 6 grupos (Controle, CIT, RSV, Al, Al+CIT e Al+RSV) e tratados durante 30 dias, a cada 48 horas. Por meio de análises comportamentais (Teste de campo aberto, Reconhecimento de objetos e Y maze), foi possível identificar a redução da memória de curto e médio prazo em Camundongos Swiss intoxicados com Al, bem como o aumento de ansiedade nesses camundongos. Também foi possível observar os efeitos protetores do RSV frente a intoxicação por Al, tanto na redução da ansiedade quanto na melhora da memória dos camundongos. As análises enzimáticas (NTPDase, 5’-NT e ADA) mostraram a atividade inflamatória desencadeada pelo Al, por meio do aumento da hidrólise de ATP no grupo intoxicado, enquanto que o RSV desempenhou efeito anti-inflamatório, reduzindo a hidrólise desse nucleotídeo. No caso da ADA, também observamos modulação positiva da atividade dessa enzima no mecanismo inflamatório desencadeado pelo Al, bem como a neuroproteção exercida pelo RSV. As análises de Western Blot (A1, A2A, P2X7, NRLP3 e BDNF), confirmaram o envolvimento do Al nos mecanismos inflamatórios relacionados a patologia da DA e a neuroproteção exercida pelo RSV nesses receptores. Com esse estudo, concluímos que o Al atua desencadeando processos inflamatórios no organismo dos camundongos, prejudicando a memória e causando estados ansiogênicos graves, e o RSV tem a capacidade de remediar esses danos causados pelo Al, atuando como neuroprotetor, melhorando a memória dos camundongos e reduzindo as atividades inflamatórias.Universidade Federal de Santa MariaBrasilBioquímicaUFSMPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaCentro de Ciências Naturais e ExatasMorsch, Vera Maria Melchiorshttp://lattes.cnpq.br/1519648219507868Reichert, KarineLoro, Vania LuciaBaldissarelli, JucimaraVisentini, Alice Estivalet2023-10-30T15:24:11Z2023-10-30T15:24:11Z2023-09-12info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/30406ark:/26339/001300000phrkporAttribution-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:UFSM2023-10-30T15:24:50Zoai:repositorio.ufsm.br:1/30406Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2024-07-29T10:48:42.220356Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Efeitos do resveratrol na sinalização purinérgica em camundongos expostos ao alumínio Resveratrol study on purinergic signaling in mice exposed to aluminum |
title |
Efeitos do resveratrol na sinalização purinérgica em camundongos expostos ao alumínio |
spellingShingle |
Efeitos do resveratrol na sinalização purinérgica em camundongos expostos ao alumínio Visentini, Alice Estivalet Alumínio Citrato Toxicidade Resveratrol Doença de Alzheimer Neurodegeneração Sistema purinérgico Sistema oxidativo Aluminum Citrate Toxicity Alzheimer's disease Neurodegeneration Purinergic system Oxidative system CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Efeitos do resveratrol na sinalização purinérgica em camundongos expostos ao alumínio |
title_full |
Efeitos do resveratrol na sinalização purinérgica em camundongos expostos ao alumínio |
title_fullStr |
Efeitos do resveratrol na sinalização purinérgica em camundongos expostos ao alumínio |
title_full_unstemmed |
Efeitos do resveratrol na sinalização purinérgica em camundongos expostos ao alumínio |
title_sort |
Efeitos do resveratrol na sinalização purinérgica em camundongos expostos ao alumínio |
author |
Visentini, Alice Estivalet |
author_facet |
Visentini, Alice Estivalet |
author_role |
author |
dc.contributor.none.fl_str_mv |
Morsch, Vera Maria Melchiors http://lattes.cnpq.br/1519648219507868 Reichert, Karine Loro, Vania Lucia Baldissarelli, Jucimara |
dc.contributor.author.fl_str_mv |
Visentini, Alice Estivalet |
dc.subject.por.fl_str_mv |
Alumínio Citrato Toxicidade Resveratrol Doença de Alzheimer Neurodegeneração Sistema purinérgico Sistema oxidativo Aluminum Citrate Toxicity Alzheimer's disease Neurodegeneration Purinergic system Oxidative system CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
topic |
Alumínio Citrato Toxicidade Resveratrol Doença de Alzheimer Neurodegeneração Sistema purinérgico Sistema oxidativo Aluminum Citrate Toxicity Alzheimer's disease Neurodegeneration Purinergic system Oxidative system CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Aluminum (Al) is a compound found in nature, and is widely used industrially, which means that humans are exposed to it daily. Due to its ability to cross the blood-brain barrier, it can accumulate in the brain in regions of the hippocampus and cortex, which is why it has been associated with neurodegeneration. Previous studies suggest that combined with citrate (CIT), its absorption and, therefore, its toxic effects are increased, favoring the emergence of pathologies such as Alzheimer's disease (AD). AD is a progressive neurodegenerative disorder that leads to gradual memory loss. The relationship between Al and purinergic neurotransmission is recent, which is why it is necessary to study alternative methods that can act to protect against possible pathological states. The use of natural substances with antioxidant properties has stood out, in this context, resveratrol (RSV) has a widely reported anti-inflammatory capacity, in addition to being a potent activator of the Sirtuin family, having been used as an antioxidant and neuroprotector when it comes to FROM THE. Its neuroprotection mechanism has not yet been fully elucidated, therefore, the study of purinergic and oxidant/antioxidant signaling becomes essential. In this study, 60 male Swiss mice were divided into 6 groups (Control, CIT, RSV, Al, Al+CIT and Al+RSV) and treated for 30 days, every 48 hours. Through behavioral analyzes (Open field test, Object recognition and Y maze), it was possible to identify the reduction of short and medium-term memory in Swiss mice intoxicated with Al, as well as the increase in anxiety in these mice. It was also possible to observe the protective effects of RSV against Al intoxication, both in reducing anxiety and improving memory in mice. Enzymatic analyzes (NTPDase, 5'-NT and ADA) showed the inflammatory activity triggered by Al, through increased ATP hydrolysis in the intoxicated group, while RSV had an anti-inflammatory effect, reducing the hydrolysis of this nucleotide. In the case of ADA, we also observed a positive modulation of the activity of this enzyme in the inflammatory mechanism triggered by Al, as well as the neuroprotection exerted by RSV. Western Blot analyzes (A1, A2A, P2X7, NRLP3 and BDNF) confirmed the involvement of Al in the inflammatory mechanisms related to AD pathology and the neuroprotection exerted by RSV in these receptors. With this study, we concluded that Al acts by triggering inflammatory processes in the body of mice, impairing memory and causing severe anxiogenic states, and RSV has the ability to remedy these damages caused by Al, acting as a neuroprotector, improving the memory of mice and reducing inflammatory activities. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-10-30T15:24:11Z 2023-10-30T15:24:11Z 2023-09-12 |
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/1/30406 |
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ark:/26339/001300000phrk |
url |
http://repositorio.ufsm.br/handle/1/30406 |
identifier_str_mv |
ark:/26339/001300000phrk |
dc.language.iso.fl_str_mv |
por |
language |
por |
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Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
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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 |
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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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