Ácido elágico e hesperidina como potenciais terapêuticos em desordens neuroinflamatórias
Ano de defesa: | 2020 |
---|---|
Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | , , , |
Tipo de documento: | Tese |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Santa Maria
Centro de Ciências Rurais |
Programa de Pós-Graduação: |
Programa de Pós-Graduação em Medicina Veterinária
|
Departamento: |
Medicina Veterinária
|
País: |
Brasil
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.ufsm.br/handle/1/22221 |
Resumo: | Neuroinflammation can negatively impact the process of neurogenesis in adult mammals in addition to being considered a risk factor for cognitive impairment and dementia. Among the experimental models of neuroinflammation, we highlight the models that use intraperitoneal (IP) applications of lipopolysaccharides (LPS) or intracerebroventricular administration (ICV) of streptozotocin (STZ). Several types of research have been carried out to search for therapeutic alternatives for neuroinflammatory disorders. Flavonoids, such as ellagic acid (EA) and hesperidin (HES), found mainly in fruits, have several beneficial effects on the body, such as antioxidant and anti-inflammatory properties, as well as reduced toxicity. In this context, this research aimed to evaluate the therapeutic potential of EA or HES in experimental models of neuroinflammation. This study was divided into two experiments. In the first one (MANUSCRIPT I), the objective of the study was to evaluate the potential of EA in an experimental model of neuroinflammation induced by multiple applications of LPS. Thirty-two male Wistar rats were used, distributed in 4 groups (n = 8): controls (CTRL+SAL) and control-treated with EA (CTRL+EA), and the groups of animals that received LPS (LPS+SAL) and (LPS+EA). The LPS groups received eight daily IP injections of LPS for eight consecutive days at a dose of 250mg/kg of body weight, dissolved in 0.9% saline while the CTRL and EA groups received only 0.9% saline vehicle in the same volume. Two hours after applications (IP), animals in the EA and LPS+EA group were treated with EA at a dose of 100mg/kg orally during the eight days of treatment. The open-field test and object recognition were performed at sixth, seventh, and eighth days of the experimental period. In the second experiment (MANUSCRIPT II), the study aimed to evaluate the effects of HES and its association with rivastigmine (RIV) on memory and oxidative parameters in a sporadic model of Alzheimer's Disease (AD) induced by ICV-STZ injection. 64 Wistar rats were used, divided into eight groups (n = 8): control (CTRL), RIV, HES, RIV+HES, STZ, STZ+RIV, and STZ, HES, STZ+RIV+HES. The rats received an ICV-STZ injection or saline solution (3 mg/kg) and were treated daily, from the fourth day, with 100 mg/kg of HES orally, for 30 days. Twenty-one days after ICV-STZ injection, oral treatment was started with 2 mg/kg of IVR that lasted for 13 days. Behavioral testing was performed by the Morris water maze 30 days after the ICV-STZ injection. In both studies, the antioxidants used (EA or HES) demonstrated the potential to reverse the harmful effects of LPS or STZ by reducing oxidative damage, increasing the antioxidant system, reducing reactive oxygen species (ROS), and improving in the animals' cognitive potential. Also, in MANUSCRIPT I, EA demonstrated immunomodulatory potential, from reduced expression of glial cells, as well as the ability to reduce acetylcholinesterase (AChE) activity and Tau phosphorylation. These results demonstrate the therapeutic potential of EA and HES in cognitive disorders secondary to neuroinflammation, which makes these antioxidants potential candidates for the treatment of neurodegenerative diseases. |
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2021-09-15T11:05:25Z2021-09-15T11:05:25Z2020-03-06http://repositorio.ufsm.br/handle/1/22221Neuroinflammation can negatively impact the process of neurogenesis in adult mammals in addition to being considered a risk factor for cognitive impairment and dementia. Among the experimental models of neuroinflammation, we highlight the models that use intraperitoneal (IP) applications of lipopolysaccharides (LPS) or intracerebroventricular administration (ICV) of streptozotocin (STZ). Several types of research have been carried out to search for therapeutic alternatives for neuroinflammatory disorders. Flavonoids, such as ellagic acid (EA) and hesperidin (HES), found mainly in fruits, have several beneficial effects on the body, such as antioxidant and anti-inflammatory properties, as well as reduced toxicity. In this context, this research aimed to evaluate the therapeutic potential of EA or HES in experimental models of neuroinflammation. This study was divided into two experiments. In the first one (MANUSCRIPT I), the objective of the study was to evaluate the potential of EA in an experimental model of neuroinflammation induced by multiple applications of LPS. Thirty-two male Wistar rats were used, distributed in 4 groups (n = 8): controls (CTRL+SAL) and control-treated with EA (CTRL+EA), and the groups of animals that received LPS (LPS+SAL) and (LPS+EA). The LPS groups received eight daily IP injections of LPS for eight consecutive days at a dose of 250mg/kg of body weight, dissolved in 0.9% saline while the CTRL and EA groups received only 0.9% saline vehicle in the same volume. Two hours after applications (IP), animals in the EA and LPS+EA group were treated with EA at a dose of 100mg/kg orally during the eight days of treatment. The open-field test and object recognition were performed at sixth, seventh, and eighth days of the experimental period. In the second experiment (MANUSCRIPT II), the study aimed to evaluate the effects of HES and its association with rivastigmine (RIV) on memory and oxidative parameters in a sporadic model of Alzheimer's Disease (AD) induced by ICV-STZ injection. 64 Wistar rats were used, divided into eight groups (n = 8): control (CTRL), RIV, HES, RIV+HES, STZ, STZ+RIV, and STZ, HES, STZ+RIV+HES. The rats received an ICV-STZ injection or saline solution (3 mg/kg) and were treated daily, from the fourth day, with 100 mg/kg of HES orally, for 30 days. Twenty-one days after ICV-STZ injection, oral treatment was started with 2 mg/kg of IVR that lasted for 13 days. Behavioral testing was performed by the Morris water maze 30 days after the ICV-STZ injection. In both studies, the antioxidants used (EA or HES) demonstrated the potential to reverse the harmful effects of LPS or STZ by reducing oxidative damage, increasing the antioxidant system, reducing reactive oxygen species (ROS), and improving in the animals' cognitive potential. Also, in MANUSCRIPT I, EA demonstrated immunomodulatory potential, from reduced expression of glial cells, as well as the ability to reduce acetylcholinesterase (AChE) activity and Tau phosphorylation. These results demonstrate the therapeutic potential of EA and HES in cognitive disorders secondary to neuroinflammation, which makes these antioxidants potential candidates for the treatment of neurodegenerative diseases.Neuroinflamação pode impactar negativamente o processo de neurogênese em adultos mamíferos, além de ser considerada fator de risco para déficit cognitivo e demência. Dentre os modelos experimentais de neuroinflamação, destacam-se os modelos que utilizam aplicações intrapeirtoneais (IP) de lipopolissacarídeos (LPS) ou administração intracerebroventricular (ICV) de estreptozotocina (STZ). Diversas pesquisas têm sido realizadas para buscar alternativas terapêuticas para desordens neuroinflamatórias. Os flavonoides, como o ácido elágico (AE) e a hesperidina (HES), provenientes principalmente de frutas, apresentam diversos efeitos benéficos ao organismo, como propriedades antioxidantes e anti-inflamatórias, e reduzida toxicidade. Nesse contexto, esta pesquisa teve por objetivo avaliar o potencial terapêutico do AE ou HES em modelos experimentais de neuroinflamação. Este estudo foi dividido em dois experimentos. No primeiro (MANUSCRITO I) o objetivo do estudo foi avaliar o potencial do AE em modelo experimental de neuroinflamação induzida por múltiplas aplicações de LPS. Foram utilizados 32 ratos machos Wistar, distribuídos em 4 grupos (n=8): controles (CTRL+SAL) e controle tratado com AE (CTRL+AE), e os grupos dos animais que receberam LPS (LPS+ SAL) e (LPS+AE). Os grupos LPS receberam 8 injeções IP diárias de LPS em 8 dias consecutivos na dose de 250mg/kg de peso corporal, dissolvida em salina 0,9% enquanto os grupos CTRL e AE receberam apenas o veículo salina 0,9% no mesmo volume. Duas horas após as aplicações (IP), os ratos do grupo AE e LPS+AE foram tratados com AE na dose de 100mg/kg por via oral durante os 8 dias de tratamento. Os testes de campo aberto e reconhecimento de objetos foram realizados nos dias seis, sete e oito do período experimental. No segundo experimento (MANUSCRITO II) o objetivo do estudo foi avaliar os efeitos da HES e sua associação com a rivastigmina (RIV) na memória e parâmetros oxidativos em um modelo de Doença de Alzheimer (DA) esporádica induzido por injeção intracerebroventricular de estreptozotocina (ICV-STZ). Foram utilizados 64 ratos Wistar, distribuídos em oito grupos (n=8): controle (CTRL), RIV, HES, RIV+HES, STZ, STZ+RIV e STZ+HES, STZ+RIV+HES. Os ratos receberam injeção ICV-STZ (3 mg/kg) ou solução salina e foram tratados diariamente, a partir do quarto dia, com 100 mg/kg de HES via oral, durante 30 dias. Aos 21 dias, pós injeção ICV-STZ, iniciou-se o tratamento oral com 2 mg/kg de RIV que teve duração de 13 dias. Realizou-se teste comportamental pelo labirinto aquático de Morris 30 dias após a injeção ICV-STZ. Em ambos estudos, os antioxidantes utilizados (AE ou HES) demonstraram potencial para reverter os efeitos deletérios do LPS ou STZ, a partir da redução do dano oxidativo, com incremento do sistema antioxidante e redução das espécies reativas de oxigênio (ERO), e melhora no potencial cognitivo dos animais. Em adição, no MANUSCRITO I, o AE demonstrou potencial imunomodulador, a partir de redução da expressão de células da glia, bem como capacidade de prevenir o aumento na atividade da acetilcolinesterase (AChE) e fosforilação da Tau. Esses resultados demonstram o potencial terapêutico do AE e HES em desordens cognitivas secundárias à neuroinflamação, o que torna esses antioxidantes potenciais candidatos para o tratamento de doenças neurodegenerativas.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESporUniversidade Federal de Santa MariaCentro de Ciências RuraisPrograma de Pós-Graduação em Medicina VeterináriaUFSMBrasilMedicina VeterináriaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessPolifenóisAntioxidantesAnti-inflamatórioEstreptozotocinaLipopolissacarídeosPolyphenolsAntioxidantsAnti-inflammatoryStreptozotocinLipopolysaccharidesCNPQ::CIENCIAS AGRARIAS::MEDICINA VETERINARIAÁcido elágico e hesperidina como potenciais terapêuticos em desordens neuroinflamatóriasElagic acid and hesperidine as potentials therapeutic for neuroinflammatory disordersinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisAndrade, Cinthia Melazzo dehttp://lattes.cnpq.br/2886709251370905Silva, Cássia Bagolin daBueno, AndressaSchetinger, Maria Rosa ChitolinaSagrillo, Michele RoratoFrança, Raqueli Teresinhahttp://lattes.cnpq.br/4082932538738730Dornelles, Guilherme Lopes500500000007600600600600600600600e0391f7d-99bf-47cd-a356-a3994d247daa20d897e7-90d4-43d9-812c-6997bfd4f6379cb2e1e1-e931-4cd7-8572-9ec81f138ad44dbb1c6f-c4e8-4f7f-8060-d29843d58a2493acb9e6-39fa-412c-84a4-a90a4863b53ec0f14923-9ad3-40fb-8062-e4ff04800646dbc195d8-80f2-447d-a0e7-865cf812f375reponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALTES_PPGMV_2020_DORNELLES_GUILHERME.pdfTES_PPGMV_2020_DORNELLES_GUILHERME.pdfTese de Doutoradoapplication/pdf2488898http://repositorio.ufsm.br/bitstream/1/22221/1/TES_PPGMV_2020_DORNELLES_GUILHERME.pdfae196a914f154a71bd05b5857ae28229MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
Ácido elágico e hesperidina como potenciais terapêuticos em desordens neuroinflamatórias |
dc.title.alternative.eng.fl_str_mv |
Elagic acid and hesperidine as potentials therapeutic for neuroinflammatory disorders |
title |
Ácido elágico e hesperidina como potenciais terapêuticos em desordens neuroinflamatórias |
spellingShingle |
Ácido elágico e hesperidina como potenciais terapêuticos em desordens neuroinflamatórias Dornelles, Guilherme Lopes Polifenóis Antioxidantes Anti-inflamatório Estreptozotocina Lipopolissacarídeos Polyphenols Antioxidants Anti-inflammatory Streptozotocin Lipopolysaccharides CNPQ::CIENCIAS AGRARIAS::MEDICINA VETERINARIA |
title_short |
Ácido elágico e hesperidina como potenciais terapêuticos em desordens neuroinflamatórias |
title_full |
Ácido elágico e hesperidina como potenciais terapêuticos em desordens neuroinflamatórias |
title_fullStr |
Ácido elágico e hesperidina como potenciais terapêuticos em desordens neuroinflamatórias |
title_full_unstemmed |
Ácido elágico e hesperidina como potenciais terapêuticos em desordens neuroinflamatórias |
title_sort |
Ácido elágico e hesperidina como potenciais terapêuticos em desordens neuroinflamatórias |
author |
Dornelles, Guilherme Lopes |
author_facet |
Dornelles, Guilherme Lopes |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Andrade, Cinthia Melazzo de |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/2886709251370905 |
dc.contributor.advisor-co1.fl_str_mv |
Silva, Cássia Bagolin da |
dc.contributor.referee1.fl_str_mv |
Bueno, Andressa |
dc.contributor.referee2.fl_str_mv |
Schetinger, Maria Rosa Chitolina |
dc.contributor.referee3.fl_str_mv |
Sagrillo, Michele Rorato |
dc.contributor.referee4.fl_str_mv |
França, Raqueli Teresinha |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/4082932538738730 |
dc.contributor.author.fl_str_mv |
Dornelles, Guilherme Lopes |
contributor_str_mv |
Andrade, Cinthia Melazzo de Silva, Cássia Bagolin da Bueno, Andressa Schetinger, Maria Rosa Chitolina Sagrillo, Michele Rorato França, Raqueli Teresinha |
dc.subject.por.fl_str_mv |
Polifenóis Antioxidantes Anti-inflamatório Estreptozotocina Lipopolissacarídeos |
topic |
Polifenóis Antioxidantes Anti-inflamatório Estreptozotocina Lipopolissacarídeos Polyphenols Antioxidants Anti-inflammatory Streptozotocin Lipopolysaccharides CNPQ::CIENCIAS AGRARIAS::MEDICINA VETERINARIA |
dc.subject.eng.fl_str_mv |
Polyphenols Antioxidants Anti-inflammatory Streptozotocin Lipopolysaccharides |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS AGRARIAS::MEDICINA VETERINARIA |
description |
Neuroinflammation can negatively impact the process of neurogenesis in adult mammals in addition to being considered a risk factor for cognitive impairment and dementia. Among the experimental models of neuroinflammation, we highlight the models that use intraperitoneal (IP) applications of lipopolysaccharides (LPS) or intracerebroventricular administration (ICV) of streptozotocin (STZ). Several types of research have been carried out to search for therapeutic alternatives for neuroinflammatory disorders. Flavonoids, such as ellagic acid (EA) and hesperidin (HES), found mainly in fruits, have several beneficial effects on the body, such as antioxidant and anti-inflammatory properties, as well as reduced toxicity. In this context, this research aimed to evaluate the therapeutic potential of EA or HES in experimental models of neuroinflammation. This study was divided into two experiments. In the first one (MANUSCRIPT I), the objective of the study was to evaluate the potential of EA in an experimental model of neuroinflammation induced by multiple applications of LPS. Thirty-two male Wistar rats were used, distributed in 4 groups (n = 8): controls (CTRL+SAL) and control-treated with EA (CTRL+EA), and the groups of animals that received LPS (LPS+SAL) and (LPS+EA). The LPS groups received eight daily IP injections of LPS for eight consecutive days at a dose of 250mg/kg of body weight, dissolved in 0.9% saline while the CTRL and EA groups received only 0.9% saline vehicle in the same volume. Two hours after applications (IP), animals in the EA and LPS+EA group were treated with EA at a dose of 100mg/kg orally during the eight days of treatment. The open-field test and object recognition were performed at sixth, seventh, and eighth days of the experimental period. In the second experiment (MANUSCRIPT II), the study aimed to evaluate the effects of HES and its association with rivastigmine (RIV) on memory and oxidative parameters in a sporadic model of Alzheimer's Disease (AD) induced by ICV-STZ injection. 64 Wistar rats were used, divided into eight groups (n = 8): control (CTRL), RIV, HES, RIV+HES, STZ, STZ+RIV, and STZ, HES, STZ+RIV+HES. The rats received an ICV-STZ injection or saline solution (3 mg/kg) and were treated daily, from the fourth day, with 100 mg/kg of HES orally, for 30 days. Twenty-one days after ICV-STZ injection, oral treatment was started with 2 mg/kg of IVR that lasted for 13 days. Behavioral testing was performed by the Morris water maze 30 days after the ICV-STZ injection. In both studies, the antioxidants used (EA or HES) demonstrated the potential to reverse the harmful effects of LPS or STZ by reducing oxidative damage, increasing the antioxidant system, reducing reactive oxygen species (ROS), and improving in the animals' cognitive potential. Also, in MANUSCRIPT I, EA demonstrated immunomodulatory potential, from reduced expression of glial cells, as well as the ability to reduce acetylcholinesterase (AChE) activity and Tau phosphorylation. These results demonstrate the therapeutic potential of EA and HES in cognitive disorders secondary to neuroinflammation, which makes these antioxidants potential candidates for the treatment of neurodegenerative diseases. |
publishDate |
2020 |
dc.date.issued.fl_str_mv |
2020-03-06 |
dc.date.accessioned.fl_str_mv |
2021-09-15T11:05:25Z |
dc.date.available.fl_str_mv |
2021-09-15T11:05:25Z |
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/1/22221 |
url |
http://repositorio.ufsm.br/handle/1/22221 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.cnpq.fl_str_mv |
500500000007 |
dc.relation.confidence.fl_str_mv |
600 600 600 600 600 600 600 |
dc.relation.authority.fl_str_mv |
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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.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Rurais |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Medicina Veterinária |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Medicina Veterinária |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Rurais |
dc.source.none.fl_str_mv |
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Universidade Federal de Santa Maria (UFSM) |
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UFSM |
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UFSM |
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Biblioteca Digital de Teses e Dissertações do UFSM |
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Biblioteca Digital de Teses e Dissertações do UFSM |
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Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
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1801485643470077952 |