Efeito da associação de vitamina D3 e curcumina nanoencapsuladas sobre a sinalização purinérgica em modelo de artrite
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/20911 |
Resumo: | Rheumatoid arthritis (RA) is a chronic, autoimmune, systemic inflammatory disease that is highly debilitating. Vitamin D3 (VD3) has an immunomodulatory role in RA, exerting an inhibitory action on T lymphocytes in the production and action of cytokines. Curcumin, a polyphenol derived from Curcuma longa, interacts with cellular and molecular targets, promoting pharmacological and immunomodulatory effects in many pathologies, including RA. Therefore, it is of scientific interest to test the therapeutic effects of these two substances combined. In order to increase the bioavailability and stability of curcumin and increase the therapeutic efficacy and bioactivity of the VD3 in the immune system, a nanoencapsulation system was used. Purinergic signaling plays a role in the modulation of inflammatory and immune responses of RA. Studies involving the evaluation of the activity of enzymes that participate in the degradation cascade of adenine nucleotides are important to verify the purinergic signaling in the regulation of the immune and inflammatory response during the clinical evolution of several diseases. The objective of this study was to evaluate the possible effects of the association of these compounds in the nanoencapsulated form on purinergic signaling by the activity of the enzymes E-ADA and E- NTPDase, in a model of arthritis induced by Freund's complete adjuvant (CFA). We also evaluated biochemical and oxidative stress parameters. Wistar rats were divided into groups with and without induction of arthritis. CFA was administered to the hind paw of the animals, after 15 days, arthritis induction, thermal hyperalgesia, paw edema, and arthritis score tests were performed. On the 15th day the treatment with VOC3 (15.84 IU / day) and curcumin 4mg / kg was started separately and in combination, or with curcumin in the free form 25mg / kg, with the vehicle or with white nanocapsules for 15 days. On the 30th day, arthritis induction, biochemical and ectoenzyme tests were performed on platelets, neutrophils, lymphocytes, myeloperoxidase (MPO) and reactive oxygen species (ROS). Liver and kidney were collected for histopathological analysis. The results demonstrate the success of the model in generating an inflammatory process, evidenced by the increase in paw edema and in the score of arthritis and hyperalgesia. No histopathological changes were observed in the hepatic analyzes of the animals and no deposition of nanocapsules was found. The increase in vascularization and disorganization of the renal glomeruli of the arthritic animals was reverted by the treatments. There was a reduction in E-NTPDase activity of neutrophils and an increase in E-ADA in neutrophils, platelets, and ADA in serum added with the decrease of E-ADA in lymphocytes suggest a proinflammatory response in induced animals. The high MPO activity in the arthritic animals confirmed the inflammatory process, however ROS levels did not change post induction and/or treatment. Both nanoencapsulated formulations have been shown to reduce the signs and symptoms of inflammation, revert changes in ectoenzyme activities, and protect liver and kidney tissues as seen in the histology and in the reduction of MPO activity. Thus, the treatments in association with nanocapsules were successful, suggesting an anti-inflammatory effect with reduction of the dose, and overcoming the difficulties of absorption and distribution of these compounds, and may serve as adjuvant therapy for the treatment of rheumatoid arthritis. |
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Efeito da associação de vitamina D3 e curcumina nanoencapsuladas sobre a sinalização purinérgica em modelo de artriteEffect of the association of vitamin D3 and curcumin nanoencapsuladas on purinergic signaling in arthritis modelArtriteVitamina D3CurcuminaNanocápsulasSistema purinérgicoArthritisVitamin D3CurcuminNanocapsulesPurinergic sistemCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICARheumatoid arthritis (RA) is a chronic, autoimmune, systemic inflammatory disease that is highly debilitating. Vitamin D3 (VD3) has an immunomodulatory role in RA, exerting an inhibitory action on T lymphocytes in the production and action of cytokines. Curcumin, a polyphenol derived from Curcuma longa, interacts with cellular and molecular targets, promoting pharmacological and immunomodulatory effects in many pathologies, including RA. Therefore, it is of scientific interest to test the therapeutic effects of these two substances combined. In order to increase the bioavailability and stability of curcumin and increase the therapeutic efficacy and bioactivity of the VD3 in the immune system, a nanoencapsulation system was used. Purinergic signaling plays a role in the modulation of inflammatory and immune responses of RA. Studies involving the evaluation of the activity of enzymes that participate in the degradation cascade of adenine nucleotides are important to verify the purinergic signaling in the regulation of the immune and inflammatory response during the clinical evolution of several diseases. The objective of this study was to evaluate the possible effects of the association of these compounds in the nanoencapsulated form on purinergic signaling by the activity of the enzymes E-ADA and E- NTPDase, in a model of arthritis induced by Freund's complete adjuvant (CFA). We also evaluated biochemical and oxidative stress parameters. Wistar rats were divided into groups with and without induction of arthritis. CFA was administered to the hind paw of the animals, after 15 days, arthritis induction, thermal hyperalgesia, paw edema, and arthritis score tests were performed. On the 15th day the treatment with VOC3 (15.84 IU / day) and curcumin 4mg / kg was started separately and in combination, or with curcumin in the free form 25mg / kg, with the vehicle or with white nanocapsules for 15 days. On the 30th day, arthritis induction, biochemical and ectoenzyme tests were performed on platelets, neutrophils, lymphocytes, myeloperoxidase (MPO) and reactive oxygen species (ROS). Liver and kidney were collected for histopathological analysis. The results demonstrate the success of the model in generating an inflammatory process, evidenced by the increase in paw edema and in the score of arthritis and hyperalgesia. No histopathological changes were observed in the hepatic analyzes of the animals and no deposition of nanocapsules was found. The increase in vascularization and disorganization of the renal glomeruli of the arthritic animals was reverted by the treatments. There was a reduction in E-NTPDase activity of neutrophils and an increase in E-ADA in neutrophils, platelets, and ADA in serum added with the decrease of E-ADA in lymphocytes suggest a proinflammatory response in induced animals. The high MPO activity in the arthritic animals confirmed the inflammatory process, however ROS levels did not change post induction and/or treatment. Both nanoencapsulated formulations have been shown to reduce the signs and symptoms of inflammation, revert changes in ectoenzyme activities, and protect liver and kidney tissues as seen in the histology and in the reduction of MPO activity. Thus, the treatments in association with nanocapsules were successful, suggesting an anti-inflammatory effect with reduction of the dose, and overcoming the difficulties of absorption and distribution of these compounds, and may serve as adjuvant therapy for the treatment of rheumatoid arthritis.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESA artrite reumatoide (AR) é uma doença inflamatória crônica, autoimune, sistêmica altamente debilitante. A vitamina D3 (VD3), possui papel imunomodulador na AR, exercendo ação inibitória sobre linfócitos T na produção e ação de citocinas. A curcumina, polifenol derivado da Curcuma longa, interage com alvos celulares e moleculares, promovendo efeitos farmacológicos e imunomoduladores em muitas patologias, incluindo AR. Portanto, é de interesse científico testar uma terapia de combinação dessas duas substâncias no tratamento desta patologia. A fim de aumentar a biodisponibilidade e estabilidade da curcumina e aumentar a eficácia terapêutica e bioatividade da VD3 no sistema imunológico um sistema de nanoencapsulação foi utilizado. A sinalização purinérgica desempenha um papel relevante na modulação das respostas inflamatórias e imunes da AR. Estudos envolvendo avaliação da atividade de enzimas que participam da cascata de degradação dos nucleotídeos da adenina são importantes para verificar a sinalização purinérgica na regulação da resposta imune e inflamatória durante a evolução clínica de várias doenças. O objetivo deste estudo foi avaliar os possíveis efeitos da associação destes compostos na forma nanoencapsulada, sobre a sinalização purinérgica por meio da atividade das enzimas E-ADA e E-NTPDase, em modelo de artrite induzida pelo adjuvante completo de Freund (CFA). Também foram avaliados parâmetro bioquímicos e de estresse oxidativo. Ratos Wistar foram divididos em grupos com e sem indução de artrite. CFA foi administrado na pata traseira dos animais, após 15 dias, foram realizados testes de indução da artrite, hiperalgésica termal, edema de pata e escore de artrite. No 15º dia iniciou-se o tratamento com nanocápsulas de VD3 (15,84 UI/dia) e curcumina 4mg/kg em separado e em associação, ou com curcumina na forma livre 25mg/kg, com o veículo ou com nanocapsulas branca, durante 15 dias. No 30º dia foram realizados novamente testes de indução da artrite, bioquímicos e atividade das ectoenzimas em plaquetas, neutrófilos, linfócitos, mieloperoxidase (MPO) e espécies reativas de oxigênio (EROS). Fígado e rim foram coletados para análises histopatológicas. Os resultados demonstram o sucesso do modelo em gerar um processo inflamatório, comprovado pelo aumento no edema de pata e no escore de artrite e da hiperalgesia. Não foram observadas alterações histopatológicas nas análises hepáticas dos animais e não foi encontrada deposição de nanocápsulas. O aumento na vascularização e desorganização dos glomérulos renais dos animais artríticos foram revertidos pelos tratamentos. Houve redução na atividade da E-NTPDase de neutrófilos e aumento na E-ADA em neutrófilos, plaquetas e ADA em soro somados com a diminuição da E-ADA em linfócitos sugerem uma resposta pró-inflamatória nos animais induzidos. A atividade de MPO elevada nos animais artríticos confirmou o processo inflamatório, contudo as EROS não se alteraram pós indução e/ou tratamento. Ambas as formulações nanoencapsuladas mostraram reduzir os sinais e sintomas da inflamação, reverter as alterações das atividades das ectoenzimas e proteger tecidos hepáticos e renais pela reversão visão histológica e de redução da MPO. Assim, os tratamentos em associação de nanocapsulas obtiveram sucesso, sugerindo efeito anti-inflamatório com redução da dose, e superação de dificuldades de absorção e distribuição desses compostos, podendo servir terapia adjuvante para o tratamento da artrite reumatoide.Universidade Federal de Santa MariaBrasilBioquímicaUFSMPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaCentro de Ciências Naturais e ExatasLeal, Daniela Bitencourt Rosahttp://lattes.cnpq.br/3639683273462361Chitolina, Maria RosaXXXXXXXXXXXXXXXxSpanevello, Rosélia MariaXXXXXXXXXXXXXXXXXXSilva, Jean Lucas Gutknecht da2021-05-18T11:17:23Z2021-05-18T11:17:23Z2019-02-19info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/20911porAttribution-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:UFSM2021-05-19T06:00:43Zoai:repositorio.ufsm.br:1/20911Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2021-05-19T06:00:43Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Efeito da associação de vitamina D3 e curcumina nanoencapsuladas sobre a sinalização purinérgica em modelo de artrite Effect of the association of vitamin D3 and curcumin nanoencapsuladas on purinergic signaling in arthritis model |
title |
Efeito da associação de vitamina D3 e curcumina nanoencapsuladas sobre a sinalização purinérgica em modelo de artrite |
spellingShingle |
Efeito da associação de vitamina D3 e curcumina nanoencapsuladas sobre a sinalização purinérgica em modelo de artrite Silva, Jean Lucas Gutknecht da Artrite Vitamina D3 Curcumina Nanocápsulas Sistema purinérgico Arthritis Vitamin D3 Curcumin Nanocapsules Purinergic sistem CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Efeito da associação de vitamina D3 e curcumina nanoencapsuladas sobre a sinalização purinérgica em modelo de artrite |
title_full |
Efeito da associação de vitamina D3 e curcumina nanoencapsuladas sobre a sinalização purinérgica em modelo de artrite |
title_fullStr |
Efeito da associação de vitamina D3 e curcumina nanoencapsuladas sobre a sinalização purinérgica em modelo de artrite |
title_full_unstemmed |
Efeito da associação de vitamina D3 e curcumina nanoencapsuladas sobre a sinalização purinérgica em modelo de artrite |
title_sort |
Efeito da associação de vitamina D3 e curcumina nanoencapsuladas sobre a sinalização purinérgica em modelo de artrite |
author |
Silva, Jean Lucas Gutknecht da |
author_facet |
Silva, Jean Lucas Gutknecht da |
author_role |
author |
dc.contributor.none.fl_str_mv |
Leal, Daniela Bitencourt Rosa http://lattes.cnpq.br/3639683273462361 Chitolina, Maria Rosa XXXXXXXXXXXXXXXx Spanevello, Rosélia Maria XXXXXXXXXXXXXXXXXX |
dc.contributor.author.fl_str_mv |
Silva, Jean Lucas Gutknecht da |
dc.subject.por.fl_str_mv |
Artrite Vitamina D3 Curcumina Nanocápsulas Sistema purinérgico Arthritis Vitamin D3 Curcumin Nanocapsules Purinergic sistem CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
topic |
Artrite Vitamina D3 Curcumina Nanocápsulas Sistema purinérgico Arthritis Vitamin D3 Curcumin Nanocapsules Purinergic sistem CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Rheumatoid arthritis (RA) is a chronic, autoimmune, systemic inflammatory disease that is highly debilitating. Vitamin D3 (VD3) has an immunomodulatory role in RA, exerting an inhibitory action on T lymphocytes in the production and action of cytokines. Curcumin, a polyphenol derived from Curcuma longa, interacts with cellular and molecular targets, promoting pharmacological and immunomodulatory effects in many pathologies, including RA. Therefore, it is of scientific interest to test the therapeutic effects of these two substances combined. In order to increase the bioavailability and stability of curcumin and increase the therapeutic efficacy and bioactivity of the VD3 in the immune system, a nanoencapsulation system was used. Purinergic signaling plays a role in the modulation of inflammatory and immune responses of RA. Studies involving the evaluation of the activity of enzymes that participate in the degradation cascade of adenine nucleotides are important to verify the purinergic signaling in the regulation of the immune and inflammatory response during the clinical evolution of several diseases. The objective of this study was to evaluate the possible effects of the association of these compounds in the nanoencapsulated form on purinergic signaling by the activity of the enzymes E-ADA and E- NTPDase, in a model of arthritis induced by Freund's complete adjuvant (CFA). We also evaluated biochemical and oxidative stress parameters. Wistar rats were divided into groups with and without induction of arthritis. CFA was administered to the hind paw of the animals, after 15 days, arthritis induction, thermal hyperalgesia, paw edema, and arthritis score tests were performed. On the 15th day the treatment with VOC3 (15.84 IU / day) and curcumin 4mg / kg was started separately and in combination, or with curcumin in the free form 25mg / kg, with the vehicle or with white nanocapsules for 15 days. On the 30th day, arthritis induction, biochemical and ectoenzyme tests were performed on platelets, neutrophils, lymphocytes, myeloperoxidase (MPO) and reactive oxygen species (ROS). Liver and kidney were collected for histopathological analysis. The results demonstrate the success of the model in generating an inflammatory process, evidenced by the increase in paw edema and in the score of arthritis and hyperalgesia. No histopathological changes were observed in the hepatic analyzes of the animals and no deposition of nanocapsules was found. The increase in vascularization and disorganization of the renal glomeruli of the arthritic animals was reverted by the treatments. There was a reduction in E-NTPDase activity of neutrophils and an increase in E-ADA in neutrophils, platelets, and ADA in serum added with the decrease of E-ADA in lymphocytes suggest a proinflammatory response in induced animals. The high MPO activity in the arthritic animals confirmed the inflammatory process, however ROS levels did not change post induction and/or treatment. Both nanoencapsulated formulations have been shown to reduce the signs and symptoms of inflammation, revert changes in ectoenzyme activities, and protect liver and kidney tissues as seen in the histology and in the reduction of MPO activity. Thus, the treatments in association with nanocapsules were successful, suggesting an anti-inflammatory effect with reduction of the dose, and overcoming the difficulties of absorption and distribution of these compounds, and may serve as adjuvant therapy for the treatment of rheumatoid arthritis. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-02-19 2021-05-18T11:17:23Z 2021-05-18T11:17:23Z |
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/1/20911 |
url |
http://repositorio.ufsm.br/handle/1/20911 |
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 |
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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 |
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Universidade Federal de Santa Maria (UFSM) |
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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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1805922056979611648 |