Efeito da quercetina na sinalização purinérgica e no metabolismo oxidativo-inflamatório em modelo de artrite
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
dARK ID: | ark:/26339/001300000mx9f |
Texto Completo: | http://repositorio.ufsm.br/handle/1/21053 |
Resumo: | Rheumatoid arthritis (RA) is a chronic, autoimmune, inflammatory disease with predominant involvement of the small joints, progressive destruction of cartilage and bone, and extra- articular manifestations such as liver, kidney, and vascular damage. The purinergic signaling system plays an important role in the modulation of inflammatory and immune responses through extracellular biomolecules, such as adenine nucleotides, and its adenosine derivative, whose extracellular concentrations are controlled by ectoenzymes (E-NTPDase, E- 5´nucleotidase, and E-ADA) present on the surface of several cells. Besides, numerous studies have demonstrated the involvement of oxidative stress in the pathogenesis of inflammatory arthropathies, such as RA. Quercetin is a flavonoid present in several foods and with well- established anti-inflammatory and antioxidant properties in different experimental models of chronic diseases. In the present study, the effect of quercetin on purinergic signaling and oxidative inflammatory metabolism in model of adjuvant-induced arthritis (AIA) was investigated. Female Wistar rats were divided into groups with and without induction of arthritis. Arthritis score, paw edema, and thermal hyperalgesia were performed before induction. In the arthritis groups, the complete Freund's adjuvant (CFA) was then injected into the hind paw and, after 15 days induction, for confirmation, these tests were repeated. On the 15th day, saline and quercetin treatments started at doses of 5, 25 and 50 mg / kg for 45 days. At the end of the treatment, the tests for evidence of arthritis were repeated, in addition to the activity of ectoenzymes in lymphocytes. Oxidative stress parameters were analyzed in serum, plasma, and hepatic and renal tissue, as well as serum hepatic enzymes, plasma myeloperoxidase activity, IFN-γ and IL-4 levels in serum, and DNA damage markers. The results demonstrated that an inflammatory process was generated, as seen by the increase in the arthritis score and paw edema and the reduction of the thermal hyperalgesia. There was also an increase in E-NTPDase activity and a decrease in E-ADA activity in lymphocytes, in addition to an increase in AST levels, myeloperoxidase activity, IFN-γ and IL-4 secretion, as well as levels of EROs in serum, liver, and kidney EROs, plasma T-BARS, increased DNA damage, and decreased antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD). The treatment with quercetin reduced the signs and symptoms of arthritis, besides altering the activities of the ectoenzymes, reducing the levels of AST and DNA damage, and protect against damage caused by oxidative stress. Thus, we can suggest that quercetin showed an excellent anti-inflammatory and antioxidant effect, proving to be a promising candidate for adjuvant therapy for the treatment of rheumatoid arthritis. |
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Efeito da quercetina na sinalização purinérgica e no metabolismo oxidativo-inflamatório em modelo de artriteEffect of quercetin on purinergic signalling and oxidative- inflammatory metabolism in arthritis modelArtriteQuercetinaSinalização purinérgicaEstresse oxidativoArthritisQuercetinPurinergic signalingOxidative stressCNPQ::CIENCIAS DA SAUDE::FARMACIARheumatoid arthritis (RA) is a chronic, autoimmune, inflammatory disease with predominant involvement of the small joints, progressive destruction of cartilage and bone, and extra- articular manifestations such as liver, kidney, and vascular damage. The purinergic signaling system plays an important role in the modulation of inflammatory and immune responses through extracellular biomolecules, such as adenine nucleotides, and its adenosine derivative, whose extracellular concentrations are controlled by ectoenzymes (E-NTPDase, E- 5´nucleotidase, and E-ADA) present on the surface of several cells. Besides, numerous studies have demonstrated the involvement of oxidative stress in the pathogenesis of inflammatory arthropathies, such as RA. Quercetin is a flavonoid present in several foods and with well- established anti-inflammatory and antioxidant properties in different experimental models of chronic diseases. In the present study, the effect of quercetin on purinergic signaling and oxidative inflammatory metabolism in model of adjuvant-induced arthritis (AIA) was investigated. Female Wistar rats were divided into groups with and without induction of arthritis. Arthritis score, paw edema, and thermal hyperalgesia were performed before induction. In the arthritis groups, the complete Freund's adjuvant (CFA) was then injected into the hind paw and, after 15 days induction, for confirmation, these tests were repeated. On the 15th day, saline and quercetin treatments started at doses of 5, 25 and 50 mg / kg for 45 days. At the end of the treatment, the tests for evidence of arthritis were repeated, in addition to the activity of ectoenzymes in lymphocytes. Oxidative stress parameters were analyzed in serum, plasma, and hepatic and renal tissue, as well as serum hepatic enzymes, plasma myeloperoxidase activity, IFN-γ and IL-4 levels in serum, and DNA damage markers. The results demonstrated that an inflammatory process was generated, as seen by the increase in the arthritis score and paw edema and the reduction of the thermal hyperalgesia. There was also an increase in E-NTPDase activity and a decrease in E-ADA activity in lymphocytes, in addition to an increase in AST levels, myeloperoxidase activity, IFN-γ and IL-4 secretion, as well as levels of EROs in serum, liver, and kidney EROs, plasma T-BARS, increased DNA damage, and decreased antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD). The treatment with quercetin reduced the signs and symptoms of arthritis, besides altering the activities of the ectoenzymes, reducing the levels of AST and DNA damage, and protect against damage caused by oxidative stress. Thus, we can suggest that quercetin showed an excellent anti-inflammatory and antioxidant effect, proving to be a promising candidate for adjuvant therapy for the treatment of rheumatoid arthritis.A artrite reumatoide (AR) é uma doença inflamatória, autoimune, crônica, com envolvimento predominante da membrana sinovial das pequenas articulações e destruição progressiva de cartilagem e osso e eventualmente são observadas manifestações extra-articulares, como danos hepáticos, renais e vasculares. O sistema de sinalização purinérgica desempenha um importante papel na modulação das respostas inflamatórias e imunes, através das biomoléculas extracelulares, como os nucleotídeos de adenina, e seu derivado adenosina, cujas concentrações extracelulares são controladas por ação de ectoenzimas (E-NTPDase, E- 5`-nucleotidase e E-ADA) presentes em superfícies de diversas células. Além disso, inúmeros estudos demonstraram o envolvimento do estresse oxidativo na patogênese das artropatias inflamatórias, como a AR. A quercetina é um flavonoide presente em diversos alimentos e com propriedades anti-inflamatórias e antioxidantes bem estabelecidas em diferentes modelos experimentais de doenças crônicas. No presente trabalho, investigou-se o efeito da quercetina na sinalização purinérgica e no metabolismo oxidativo-inflamatório em um modelo de artrite induzida por adjuvante (AIA). Ratos Wistar fêmeas foram divididos em grupos com e sem indução de artrite. Foram realizados testes de escore de artrite, edema de pata e hiperalgesia termal antes da indução. O adjuvante completo de Freund (CFA) foi injetado na pata traseira e, após 15 dias da indução, para a confirmação, estes testes foram repetidos. No 15º dia iniciou-se o tratamento com salina e quercetina nas doses de 5, 25 e 50 mg/kg, durante 45 dias. No fim do tratamento, os testes para comprovação da artrite foram novamente repetidos, além da atividade das ectoenzimas em linfócitos. Avaliações dos parâmetros do estresse oxidativo foram analisadas em soro, plasma e em tecido hepático e renal, além da dosagem das enzimas hepáticas no soro, da atividade da mieloperoxidase no plasma, bem como das citocinas IFN-γ e IL-4 e marcadores de dano ao DNA. Os resultados demonstraram que o modelo foi capaz de gerar um processo inflamatório, devido ao aumento do escore da artrite, do edema de pata e da diminuição da hiperalgesia termal. Observou-se também um aumento da atividade da E-NTPDase e diminuição da E-ADA em linfócitos, além de um aumento nos níveis de AST, da atividade da mieloperoxidase, da secreção do IFN-γ e da IL-4, bem como dos níveis de EROs em soro, fígado e rim, TBARS em plasma, aumento do dano ao DNA e diminuição das enzimas antioxidantes catalase (CAT) e superóxido dismutase (SOD). O tratamento com a quercetina foi capaz de reduzir os sinais e sintomas do processo inflamatório, além de alterar as atividades das ectoenzimas, reduzir os níveis de AST e os níveis de dano ao DNA, e ainda de proteger contra os danos causados pelo estresse oxidativo. Assim, podemos sugerir que a quercetina evidenciou excelente efeito anti-inflamatório, e antioxidante, mostrando ser um candidato promissor para a terapia adjuvante para o tratamento da artrite reumatoide.Universidade Federal de Santa MariaBrasilCiências da SaúdeUFSMPrograma de Pós-Graduação em Ciências FarmacêuticasCentro de Ciências da SaúdeLeal, Daniela Bitencourt Rosahttp://lattes.cnpq.br/3639683273462361Silva, José Edson Paz daXXXXXXXXXXXXXXXChitolina, Maria RosaXXXXXXXXXXXXXXXXXXPereira, PatríciaXXXXXXXXXXXXXXXRomão, Pedro Roosevelt TorresXXXXXXXXXXXXXXXXXXSaccol, Renata da Silva Pereira2021-06-02T19:48:04Z2021-06-02T19:48:04Z2018-12-17info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/21053ark:/26339/001300000mx9fporAttribution-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:UFSM2021-06-03T06:03:03Zoai:repositorio.ufsm.br:1/21053Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2021-06-03T06:03:03Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Efeito da quercetina na sinalização purinérgica e no metabolismo oxidativo-inflamatório em modelo de artrite Effect of quercetin on purinergic signalling and oxidative- inflammatory metabolism in arthritis model |
title |
Efeito da quercetina na sinalização purinérgica e no metabolismo oxidativo-inflamatório em modelo de artrite |
spellingShingle |
Efeito da quercetina na sinalização purinérgica e no metabolismo oxidativo-inflamatório em modelo de artrite Saccol, Renata da Silva Pereira Artrite Quercetina Sinalização purinérgica Estresse oxidativo Arthritis Quercetin Purinergic signaling Oxidative stress CNPQ::CIENCIAS DA SAUDE::FARMACIA |
title_short |
Efeito da quercetina na sinalização purinérgica e no metabolismo oxidativo-inflamatório em modelo de artrite |
title_full |
Efeito da quercetina na sinalização purinérgica e no metabolismo oxidativo-inflamatório em modelo de artrite |
title_fullStr |
Efeito da quercetina na sinalização purinérgica e no metabolismo oxidativo-inflamatório em modelo de artrite |
title_full_unstemmed |
Efeito da quercetina na sinalização purinérgica e no metabolismo oxidativo-inflamatório em modelo de artrite |
title_sort |
Efeito da quercetina na sinalização purinérgica e no metabolismo oxidativo-inflamatório em modelo de artrite |
author |
Saccol, Renata da Silva Pereira |
author_facet |
Saccol, Renata da Silva Pereira |
author_role |
author |
dc.contributor.none.fl_str_mv |
Leal, Daniela Bitencourt Rosa http://lattes.cnpq.br/3639683273462361 Silva, José Edson Paz da XXXXXXXXXXXXXXX Chitolina, Maria Rosa XXXXXXXXXXXXXXXXXX Pereira, Patrícia XXXXXXXXXXXXXXX Romão, Pedro Roosevelt Torres XXXXXXXXXXXXXXXXXX |
dc.contributor.author.fl_str_mv |
Saccol, Renata da Silva Pereira |
dc.subject.por.fl_str_mv |
Artrite Quercetina Sinalização purinérgica Estresse oxidativo Arthritis Quercetin Purinergic signaling Oxidative stress CNPQ::CIENCIAS DA SAUDE::FARMACIA |
topic |
Artrite Quercetina Sinalização purinérgica Estresse oxidativo Arthritis Quercetin Purinergic signaling Oxidative stress CNPQ::CIENCIAS DA SAUDE::FARMACIA |
description |
Rheumatoid arthritis (RA) is a chronic, autoimmune, inflammatory disease with predominant involvement of the small joints, progressive destruction of cartilage and bone, and extra- articular manifestations such as liver, kidney, and vascular damage. The purinergic signaling system plays an important role in the modulation of inflammatory and immune responses through extracellular biomolecules, such as adenine nucleotides, and its adenosine derivative, whose extracellular concentrations are controlled by ectoenzymes (E-NTPDase, E- 5´nucleotidase, and E-ADA) present on the surface of several cells. Besides, numerous studies have demonstrated the involvement of oxidative stress in the pathogenesis of inflammatory arthropathies, such as RA. Quercetin is a flavonoid present in several foods and with well- established anti-inflammatory and antioxidant properties in different experimental models of chronic diseases. In the present study, the effect of quercetin on purinergic signaling and oxidative inflammatory metabolism in model of adjuvant-induced arthritis (AIA) was investigated. Female Wistar rats were divided into groups with and without induction of arthritis. Arthritis score, paw edema, and thermal hyperalgesia were performed before induction. In the arthritis groups, the complete Freund's adjuvant (CFA) was then injected into the hind paw and, after 15 days induction, for confirmation, these tests were repeated. On the 15th day, saline and quercetin treatments started at doses of 5, 25 and 50 mg / kg for 45 days. At the end of the treatment, the tests for evidence of arthritis were repeated, in addition to the activity of ectoenzymes in lymphocytes. Oxidative stress parameters were analyzed in serum, plasma, and hepatic and renal tissue, as well as serum hepatic enzymes, plasma myeloperoxidase activity, IFN-γ and IL-4 levels in serum, and DNA damage markers. The results demonstrated that an inflammatory process was generated, as seen by the increase in the arthritis score and paw edema and the reduction of the thermal hyperalgesia. There was also an increase in E-NTPDase activity and a decrease in E-ADA activity in lymphocytes, in addition to an increase in AST levels, myeloperoxidase activity, IFN-γ and IL-4 secretion, as well as levels of EROs in serum, liver, and kidney EROs, plasma T-BARS, increased DNA damage, and decreased antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD). The treatment with quercetin reduced the signs and symptoms of arthritis, besides altering the activities of the ectoenzymes, reducing the levels of AST and DNA damage, and protect against damage caused by oxidative stress. Thus, we can suggest that quercetin showed an excellent anti-inflammatory and antioxidant effect, proving to be a promising candidate for adjuvant therapy for the treatment of rheumatoid arthritis. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-12-17 2021-06-02T19:48:04Z 2021-06-02T19:48:04Z |
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/1/21053 |
dc.identifier.dark.fl_str_mv |
ark:/26339/001300000mx9f |
url |
http://repositorio.ufsm.br/handle/1/21053 |
identifier_str_mv |
ark:/26339/001300000mx9f |
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 Ciências da Saúde UFSM Programa de Pós-Graduação em Ciências Farmacêuticas Centro de Ciências da Saúde |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Ciências da Saúde UFSM Programa de Pós-Graduação em Ciências Farmacêuticas Centro de Ciências da Saúde |
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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1815172364523012096 |