Efeitos do resveratrol na sinalização purinérgica em camundongos expostos ao alumínio

Detalhes bibliográficos
Autor(a) principal: Visentini, Alice Estivalet
Data de Publicação: 2023
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Manancial - Repositório Digital da UFSM
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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spelling 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/1/30406porAttribution-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:2023-10-30T15:24:50Manancial - 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
url http://repositorio.ufsm.br/handle/1/30406
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
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