Estudo do efeito da fração não dialisável do látex de Calotropis procera (ait) R. Br em modelos experimentais de inflamação, com ênfase em artrite

Detalhes bibliográficos
Ano de defesa: 2007
Autor(a) principal: Cavalcante, Cid Freitas
Orientador(a): Vale, Marcus Raimundo
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Não Informado pela instituição
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: http://www.repositorio.ufc.br/handle/riufc/2273
Resumo: The objective of this dissertation was to investigate the effect of the latex from Calotropis procera in experimental models of inflammation, with special focus on arthritis. The plant belongs to Asclepiadaceae family and is largely found in Northeast of Brazil. The plant latex presents clear anti-inflammatory effects, which is kept by its non-dialyzable protein fraction (NDPF), a less toxic and rubber free fraction. NDPF was obtained according to a procedure established by our group, which, in short, involves several steps of centrifugation and dialysis. Male Wistar rats (230 – 280g) and Balb/c and Swiss male mice (18 – 35g) were organized in groups of 6 animals: a control group (no treatment), a sham group, in which only the inflammatory event was induced (arthritis by zymosan – AZy), an antigen-induced arthritis group (AIA), an infectious peritonitis group (IP) and an experimental group, treated with NDPF. The AZy group was submitted to an articular incapacitation test to measure the paw elevation time (PET, in seconds) and, after sacrifice, total and differential cell count in the intra-articular fluid, histopathological study of the articulation, vascular permeabilization, ADA and TNF-α assays. The results were expressed in means + S.E.M. and significative differences were accepted if p<0.05 (ANOVA/Bonferroni). NDPF inhibited PET in AZy with a maximum effect in the dose of 3mg/kg, at 4h after inflammation induction. There was also a significative reduction of vascular permeability, TNF-α and ADA serum levels and an improvement of the histopathological profile. NDPF also reduced the intra-articular influx of cells in AZy and AIA, especially of neutrophils. In IP, NDPF inhibited the cellular migration and the levels of ADA. So, the results confirmed the expected anti-inflammatory effect of NDPF in arthritis and peritonitis models and suggested a possible mechanism of action involving either an increase of adenosine concentration due to the reduction of ADA levels or an inhibition of TNF-α or both events. Finally, the NDPF chronical toxicity was evaluated confirming that the dose of 10mg/Kg presents well defined pharmacological effects without significant alterations on the animal parameters. The characteristics of NDPF open an interesting possibility for alternative therapy to substitute the toxic effects of steroidal and some non-steroidal drugs, used in rheumatoid diseases, so prevalent among our population.
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spelling Cavalcante, Cid FreitasVale, Marcus Raimundo2012-03-12T12:13:24Z2012-03-12T12:13:24Z2007CAVALCANTE, C. F. Estudo do efeito da fração não dialisável do látex de Calotropis procera (ait) R. Br em modelos experimentais de inflamação, com ênfase em artrite. 2007. 89 f. Dissertação (Mestrado em Farmacologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2007.http://www.repositorio.ufc.br/handle/riufc/2273The objective of this dissertation was to investigate the effect of the latex from Calotropis procera in experimental models of inflammation, with special focus on arthritis. The plant belongs to Asclepiadaceae family and is largely found in Northeast of Brazil. The plant latex presents clear anti-inflammatory effects, which is kept by its non-dialyzable protein fraction (NDPF), a less toxic and rubber free fraction. NDPF was obtained according to a procedure established by our group, which, in short, involves several steps of centrifugation and dialysis. Male Wistar rats (230 – 280g) and Balb/c and Swiss male mice (18 – 35g) were organized in groups of 6 animals: a control group (no treatment), a sham group, in which only the inflammatory event was induced (arthritis by zymosan – AZy), an antigen-induced arthritis group (AIA), an infectious peritonitis group (IP) and an experimental group, treated with NDPF. The AZy group was submitted to an articular incapacitation test to measure the paw elevation time (PET, in seconds) and, after sacrifice, total and differential cell count in the intra-articular fluid, histopathological study of the articulation, vascular permeabilization, ADA and TNF-α assays. The results were expressed in means + S.E.M. and significative differences were accepted if p<0.05 (ANOVA/Bonferroni). NDPF inhibited PET in AZy with a maximum effect in the dose of 3mg/kg, at 4h after inflammation induction. There was also a significative reduction of vascular permeability, TNF-α and ADA serum levels and an improvement of the histopathological profile. NDPF also reduced the intra-articular influx of cells in AZy and AIA, especially of neutrophils. In IP, NDPF inhibited the cellular migration and the levels of ADA. So, the results confirmed the expected anti-inflammatory effect of NDPF in arthritis and peritonitis models and suggested a possible mechanism of action involving either an increase of adenosine concentration due to the reduction of ADA levels or an inhibition of TNF-α or both events. Finally, the NDPF chronical toxicity was evaluated confirming that the dose of 10mg/Kg presents well defined pharmacological effects without significant alterations on the animal parameters. The characteristics of NDPF open an interesting possibility for alternative therapy to substitute the toxic effects of steroidal and some non-steroidal drugs, used in rheumatoid diseases, so prevalent among our population.Tendo em vista a prevalência de doenças inflamatórias reumáticas tais como a artrite reumatóide em nosso meio e a necessidade constante de novas terapias alternativas às drogas esteróides e não esteroidais, que apresentam tantos efeitos nocivos em uso prolongado, decidimos investigar a ação do látex de Calotropis procera em modelos experimentais de inflamação, com foco na artrite. O látex dessa planta da família Asclepiadaceae, vastamente encontrada no Nordeste brasileiro, tem efeitos sabidamente antiinflamatórios em algumas situações, notadamente a sua fração protéica majoritária, não dialisável (FNDL), menos tóxica e desprovida de borracha. A fração foi obtida a partir de um protocolo estabelecido por nossos colaboradores, que, em suma envolve várias etapas de centrifugação e diálise até o produto final liofilizado. Utilizamos ratos Wistar machos com peso entre 230 e 280g e camundongos, Balb/c e Swiss, pesando entre 18 e 35g, em grupos de seis indivíduos nos quais um controle, outro sham em que foi induzido o evento inflamatório (artrite por Zy - AZy, artrite induzida por antígeno - AIA ou peritonite infecciosa - PI) e o experimental no qual foi tratado com FNDL. O grupo AZy foi submetido a teste de incapacitação articular pelo modelo de tempo de suspensão da pata (TSP) e, após sacrifício, à contagem de células total e diferencial no lavado articular, estudo histopatológico da articulação, avaliação de permeabilidade vascular, dosagem de ADA e TNF-α. Os resultados foram expressos em média ± e.p.m. e comparados em testes estatísticos ANOVA/Bonferroni, admitindo-se P<0.05 para significância. A FNDL inibiu o TSP na AZy com efeito máximo na dose de 3mg/kg no t = 4h. Houve também redução significativa da permeabilidade vascular, nos níveis séricos de TNF-α e de ADA, e melhora no quadro histopatológico. Também reduziu o influxo celular sinovial na AZy e AIA, sobretudo de neutrófilos. Na PI, inibiu a migração celular e os níveis de ADA. Dessa forma, os resultados confirmaram o efeito antiinflamatório da FNDL nestes modelos de artrite e peritonite e sugeriram um possível mecanismo de ação relacionado a um aumento da adenosina, por conta da redução dos níveis de ADA, ou por inibição do TNF-α. Por fim procedemos a avaliação da toxicidade da droga em tratamento crônico, constatando que a dose de 10mg/Kg apresenta bons efeitos farmacológicos sem alterações significativas nos parâmetros selecionados.ArtriteLátexZimosanEstudo do efeito da fração não dialisável do látex de Calotropis procera (ait) R. Br em modelos experimentais de inflamação, com ênfase em artriteStudy of the effect of the non-dialyzable fraction of Calotropis procera (Ait) R. Br latex in experimental models of inflammation, with emphasis in arthritisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccessORIGINAL2007_dis_cfcavalcante.pdf2007_dis_cfcavalcante.pdfapplication/pdf571371http://repositorio.ufc.br/bitstream/riufc/2273/1/2007_dis_cfcavalcante.pdf9d6fb276b87dfaccfb5726f2ee96e864MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/2273/2/license.txt8a4605be74aa9ea9d79846c1fba20a33MD52riufc/22732022-08-22 12:29:34.599oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2022-08-22T15:29:34Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Estudo do efeito da fração não dialisável do látex de Calotropis procera (ait) R. Br em modelos experimentais de inflamação, com ênfase em artrite
dc.title.en.pt_BR.fl_str_mv Study of the effect of the non-dialyzable fraction of Calotropis procera (Ait) R. Br latex in experimental models of inflammation, with emphasis in arthritis
title Estudo do efeito da fração não dialisável do látex de Calotropis procera (ait) R. Br em modelos experimentais de inflamação, com ênfase em artrite
spellingShingle Estudo do efeito da fração não dialisável do látex de Calotropis procera (ait) R. Br em modelos experimentais de inflamação, com ênfase em artrite
Cavalcante, Cid Freitas
Artrite
Látex
Zimosan
title_short Estudo do efeito da fração não dialisável do látex de Calotropis procera (ait) R. Br em modelos experimentais de inflamação, com ênfase em artrite
title_full Estudo do efeito da fração não dialisável do látex de Calotropis procera (ait) R. Br em modelos experimentais de inflamação, com ênfase em artrite
title_fullStr Estudo do efeito da fração não dialisável do látex de Calotropis procera (ait) R. Br em modelos experimentais de inflamação, com ênfase em artrite
title_full_unstemmed Estudo do efeito da fração não dialisável do látex de Calotropis procera (ait) R. Br em modelos experimentais de inflamação, com ênfase em artrite
title_sort Estudo do efeito da fração não dialisável do látex de Calotropis procera (ait) R. Br em modelos experimentais de inflamação, com ênfase em artrite
author Cavalcante, Cid Freitas
author_facet Cavalcante, Cid Freitas
author_role author
dc.contributor.author.fl_str_mv Cavalcante, Cid Freitas
dc.contributor.advisor1.fl_str_mv Vale, Marcus Raimundo
contributor_str_mv Vale, Marcus Raimundo
dc.subject.por.fl_str_mv Artrite
Látex
Zimosan
topic Artrite
Látex
Zimosan
description The objective of this dissertation was to investigate the effect of the latex from Calotropis procera in experimental models of inflammation, with special focus on arthritis. The plant belongs to Asclepiadaceae family and is largely found in Northeast of Brazil. The plant latex presents clear anti-inflammatory effects, which is kept by its non-dialyzable protein fraction (NDPF), a less toxic and rubber free fraction. NDPF was obtained according to a procedure established by our group, which, in short, involves several steps of centrifugation and dialysis. Male Wistar rats (230 – 280g) and Balb/c and Swiss male mice (18 – 35g) were organized in groups of 6 animals: a control group (no treatment), a sham group, in which only the inflammatory event was induced (arthritis by zymosan – AZy), an antigen-induced arthritis group (AIA), an infectious peritonitis group (IP) and an experimental group, treated with NDPF. The AZy group was submitted to an articular incapacitation test to measure the paw elevation time (PET, in seconds) and, after sacrifice, total and differential cell count in the intra-articular fluid, histopathological study of the articulation, vascular permeabilization, ADA and TNF-α assays. The results were expressed in means + S.E.M. and significative differences were accepted if p<0.05 (ANOVA/Bonferroni). NDPF inhibited PET in AZy with a maximum effect in the dose of 3mg/kg, at 4h after inflammation induction. There was also a significative reduction of vascular permeability, TNF-α and ADA serum levels and an improvement of the histopathological profile. NDPF also reduced the intra-articular influx of cells in AZy and AIA, especially of neutrophils. In IP, NDPF inhibited the cellular migration and the levels of ADA. So, the results confirmed the expected anti-inflammatory effect of NDPF in arthritis and peritonitis models and suggested a possible mechanism of action involving either an increase of adenosine concentration due to the reduction of ADA levels or an inhibition of TNF-α or both events. Finally, the NDPF chronical toxicity was evaluated confirming that the dose of 10mg/Kg presents well defined pharmacological effects without significant alterations on the animal parameters. The characteristics of NDPF open an interesting possibility for alternative therapy to substitute the toxic effects of steroidal and some non-steroidal drugs, used in rheumatoid diseases, so prevalent among our population.
publishDate 2007
dc.date.issued.fl_str_mv 2007
dc.date.accessioned.fl_str_mv 2012-03-12T12:13:24Z
dc.date.available.fl_str_mv 2012-03-12T12:13:24Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
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dc.identifier.citation.fl_str_mv CAVALCANTE, C. F. Estudo do efeito da fração não dialisável do látex de Calotropis procera (ait) R. Br em modelos experimentais de inflamação, com ênfase em artrite. 2007. 89 f. Dissertação (Mestrado em Farmacologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2007.
dc.identifier.uri.fl_str_mv http://www.repositorio.ufc.br/handle/riufc/2273
identifier_str_mv CAVALCANTE, C. F. Estudo do efeito da fração não dialisável do látex de Calotropis procera (ait) R. Br em modelos experimentais de inflamação, com ênfase em artrite. 2007. 89 f. Dissertação (Mestrado em Farmacologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2007.
url http://www.repositorio.ufc.br/handle/riufc/2273
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