Modificação da resposta inflamatória sistêmica em ratos inoculados com carcinossarcoma 256 de Walker : papel da degranulação mastocitária

Detalhes bibliográficos
Autor(a) principal: Barbosa, André Luiz dos Reis
Data de Publicação: 2007
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da Universidade Federal do Ceará (UFC)
Texto Completo: http://www.repositorio.ufc.br/handle/riufc/2205
Resumo: Our objective was to evaluate the effect of the 256 Walker carcinossarcoma inoculation, as well as the time course of tumoral development, upon the acute inflammatory response in rats. Wistar rats, 180-220g, received intramuscular 106 tumor cells injections. At the end of 4, 7 or 10 days, wistar rats were separated into 4 groups, with 6 animals per group. The control group, were not inoculated with tumoral cells. Several parameters were evaluated: paw edema induced by carrageenan (Cg; 300μg/hind) or dextran (Dxt, 500μg/hind paw), myeloperoxidase activity (MPO), neutrophil migration to peritoneal cavity induced by carrageenan, cutaneous vascular permeability induced by bradykinin (2μg/site), serotonin (1μg/site), histamine (30μg/site), substance P (250ng/site), capsaicin (50μg/site) or 48/80 compound (1 μg/site) and mast cell degranulation induced by 48/80 compound. Paw edema was evaluated in the contra lateral hind paw of the tumor and measured at 0, 1, 2, 3 and 4h for Cg, and 0, 30’, 1, 2, 3 and 4h.for Dxt by plethysmometry. Neutrophil migration was induced by Cg injection in the contralateral hind paw or in the peritoneal cavity. After 4h, rats were sacrificed and the skin of the hind paw was harvested to measure neutrophil infiltration by MPO assay. Neutrophil migration induced by Cg was also evaluated in the peritoneal cavity, with the total e differential leucocytes counted. In order to measure cutaneous vascular permeability, immediately after intradermic stimulus injections (bradykinin, histamine, serotonin, substance P, capsaicin or 48/80 compound) Evans Blue dye was administrated (0,1mL/100g of per animal) by endovenous route. After 30 min rats were sacrificed and the skin was harvested to evaluate Evans Blue extravasations by spectrofotometry. Mast cells degranulation was evaluated in the in mesentery incubated with 48/80 compound and colored with toluidine blue. Our results shows that, in animals inoculated with the carcinossarcoma, there was a significant inhibition in the Cg and Dxt- induced paw edema, with maximal effect at the 7th and 10th days. There were no differences in MPO activity and neither in the peritoneal neutrophil infiltration induced by Cg in rats inoculated with the carcinossarcoma when compares to normal animals. After 4 and 7 days of the tumor inoculation, we observed a significant inhibition of the vascular permeability induced only by bradikinin, serotonin and 48/80 compound.. In the 10th day after the carcinossarcoma inoculation, there was a significant inhibition of the vascular permeability induced by all inflammatory stimulus tested, when we compared animals not inoculated. Mast cell degranulation was decreased in the 4th, 7th and 10th days after carcinossarcoma inoculation. These results suggested that the tumor microenvironment decreased the acute inflammatory response probably due to a inhibition of the mast cell degranulation.
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spelling Modificação da resposta inflamatória sistêmica em ratos inoculados com carcinossarcoma 256 de Walker : papel da degranulação mastocitáriaModification of the systemic inflammatory response in rats with carcinossarcoma 256 Walker : Role of mast cell degranulationCarcinossarcomaCarcinomaCarcinoma 256 de WalkerMastócitosInflamaçãoOur objective was to evaluate the effect of the 256 Walker carcinossarcoma inoculation, as well as the time course of tumoral development, upon the acute inflammatory response in rats. Wistar rats, 180-220g, received intramuscular 106 tumor cells injections. At the end of 4, 7 or 10 days, wistar rats were separated into 4 groups, with 6 animals per group. The control group, were not inoculated with tumoral cells. Several parameters were evaluated: paw edema induced by carrageenan (Cg; 300μg/hind) or dextran (Dxt, 500μg/hind paw), myeloperoxidase activity (MPO), neutrophil migration to peritoneal cavity induced by carrageenan, cutaneous vascular permeability induced by bradykinin (2μg/site), serotonin (1μg/site), histamine (30μg/site), substance P (250ng/site), capsaicin (50μg/site) or 48/80 compound (1 μg/site) and mast cell degranulation induced by 48/80 compound. Paw edema was evaluated in the contra lateral hind paw of the tumor and measured at 0, 1, 2, 3 and 4h for Cg, and 0, 30’, 1, 2, 3 and 4h.for Dxt by plethysmometry. Neutrophil migration was induced by Cg injection in the contralateral hind paw or in the peritoneal cavity. After 4h, rats were sacrificed and the skin of the hind paw was harvested to measure neutrophil infiltration by MPO assay. Neutrophil migration induced by Cg was also evaluated in the peritoneal cavity, with the total e differential leucocytes counted. In order to measure cutaneous vascular permeability, immediately after intradermic stimulus injections (bradykinin, histamine, serotonin, substance P, capsaicin or 48/80 compound) Evans Blue dye was administrated (0,1mL/100g of per animal) by endovenous route. After 30 min rats were sacrificed and the skin was harvested to evaluate Evans Blue extravasations by spectrofotometry. Mast cells degranulation was evaluated in the in mesentery incubated with 48/80 compound and colored with toluidine blue. Our results shows that, in animals inoculated with the carcinossarcoma, there was a significant inhibition in the Cg and Dxt- induced paw edema, with maximal effect at the 7th and 10th days. There were no differences in MPO activity and neither in the peritoneal neutrophil infiltration induced by Cg in rats inoculated with the carcinossarcoma when compares to normal animals. After 4 and 7 days of the tumor inoculation, we observed a significant inhibition of the vascular permeability induced only by bradikinin, serotonin and 48/80 compound.. In the 10th day after the carcinossarcoma inoculation, there was a significant inhibition of the vascular permeability induced by all inflammatory stimulus tested, when we compared animals not inoculated. Mast cell degranulation was decreased in the 4th, 7th and 10th days after carcinossarcoma inoculation. These results suggested that the tumor microenvironment decreased the acute inflammatory response probably due to a inhibition of the mast cell degranulation.No presente estudo avaliou-se os efeitos da inoculação do carcinosarcoma 256 de Walker, bem como o curso de seu desenvolvimento, sobre a reação inflamatória sistêmica. Ratos Wistar machos, pesando entre 180 a 220g, foram inoculados, por via intramuscular, com 106 células tumorais na coxa direita. Os experimentos foram realizados após o 4º, 7º e 10º dias (4D, 7D e 10D) da inoculação do carcinossarcoma 256 de Walker. O grupo controle não foi inoculado as células tumorais. Os ratos foram divididos em grupos experimentais com n = 6, nos quais foram avaliados os seguintes parâmetros: edema de pata por carragenina (Cg; 300μg/pata direita) ou dextrana (Dxt; 500μg/pata direita), atividade da enzima mieloperoxidase (MPO), migração de neutrófilos para cavidade peritoneal induzidas por carragenina (Cg; 300μg/pata direita), permeabilidade vascular cutânea induzidas por bradicinina (2μg/sítio), histamina (30μg/sítio), serotonina (1μg/sítio), substância P (250ng/sítio), capsaicina (50μg/sítio) ou composto 48/80 (1μg/sítio) e degranulação mastocitária induzida por composto 48/80. A intensidade do edema foi avaliada na pata contralateral ao tumor 1, 2, 3 e 4 hs (Cg) e 30’ ,1 2, 3, ,4 hs (Dxt) por pletismometria. A migração de neutrófilos foi induzida pela administração de Cg (300μg/pata) na pata contralateral ao tumor ou na cavidade peritoneal. Após 4 horas, os ratos foram sacrificados e as peles das patas foram retiradas para medir indiretamente a infiltração de neutrófilos, pela técnica da dosagem da atividade da MPO, e a migração de neutrófilos para cavidade peritoneal foi avaliada através da contagem total e diferencial de leucócitos. Em relação a permeabilidade vascular cutânea, imediatamente após as injeções intradérmicas dos estímulos (bradicinina, histamina, serotonina, substância P, capsaicina ou composto 48/80), foi administrado azul de Evans (0,1mL/100g do animal), na veia do plexo peniano. Após 30 min, os ratos foram sacrificados e a pele do dorso retirada, para avaliar o extravasamento do azul de Evans por espectrometria. A degranulação de mastócitos do mesentério foi avaliada após coloração com azul de toluidina, sendo contados os mastócitos degranulados num total de 100 células. Os animais com tumor apresentaram uma inibição significativa do edema de pata, com efeito máximo observado nos 7 º e 10 º dias, tanto com a Cg, quanto com Dxt, quando comparados com o controle sem tumor. Em nenhum dos dias estudados, foram observadas diferenças na atividade da MPO na pata e nem na avaliação da migração de neutrófilos para a cavidade péritoneal induzidas por Cg. Após 4 e 7 dias da inoculação do tumor, o animais apresentaram uma significativa diminuição na permeabilidade vascular cutânea induzida por bradicinina, serotonina, e composto 48/80. No entanto, o aumento da permeabilidade vascular induzida por histamina, substância P e capsaicina não foi alterada nesses dois dias. No 10 º dia, observou-se uma diminuição da permeabilidade vascular induzida por todos os estímulos quando comparado com o grupo sem tumor. A degranulação mastócitária foi inibida em animais com tumor nos 4º, 7º e 10º dias em comparação com o grupo controle. Tais dados sugerem que o microambiente do tumor de Walker diminui o curso da resposta inflamatória através da inibição da degranulação dos mastocitos.Souza , Marcellus Henrique Loiola Ponte deBarbosa, André Luiz dos Reis2012-03-07T11:38:06Z2012-03-07T11:38:06Z2007info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfBARBOSA, A. L. dos R. Modificação da resposta inflamatória sistêmica em ratos inoculados com carcinossarcoma 256 de Walker : papel da degranulação mastocitária. 2007. 135 f. Dissertação (Mestrado em Farmacologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2007.http://www.repositorio.ufc.br/handle/riufc/2205porreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccess2021-06-29T19:06:54Zoai:repositorio.ufc.br:riufc/2205Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2021-06-29T19:06:54Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.none.fl_str_mv Modificação da resposta inflamatória sistêmica em ratos inoculados com carcinossarcoma 256 de Walker : papel da degranulação mastocitária
Modification of the systemic inflammatory response in rats with carcinossarcoma 256 Walker : Role of mast cell degranulation
title Modificação da resposta inflamatória sistêmica em ratos inoculados com carcinossarcoma 256 de Walker : papel da degranulação mastocitária
spellingShingle Modificação da resposta inflamatória sistêmica em ratos inoculados com carcinossarcoma 256 de Walker : papel da degranulação mastocitária
Barbosa, André Luiz dos Reis
Carcinossarcoma
Carcinoma
Carcinoma 256 de Walker
Mastócitos
Inflamação
title_short Modificação da resposta inflamatória sistêmica em ratos inoculados com carcinossarcoma 256 de Walker : papel da degranulação mastocitária
title_full Modificação da resposta inflamatória sistêmica em ratos inoculados com carcinossarcoma 256 de Walker : papel da degranulação mastocitária
title_fullStr Modificação da resposta inflamatória sistêmica em ratos inoculados com carcinossarcoma 256 de Walker : papel da degranulação mastocitária
title_full_unstemmed Modificação da resposta inflamatória sistêmica em ratos inoculados com carcinossarcoma 256 de Walker : papel da degranulação mastocitária
title_sort Modificação da resposta inflamatória sistêmica em ratos inoculados com carcinossarcoma 256 de Walker : papel da degranulação mastocitária
author Barbosa, André Luiz dos Reis
author_facet Barbosa, André Luiz dos Reis
author_role author
dc.contributor.none.fl_str_mv Souza , Marcellus Henrique Loiola Ponte de
dc.contributor.author.fl_str_mv Barbosa, André Luiz dos Reis
dc.subject.por.fl_str_mv Carcinossarcoma
Carcinoma
Carcinoma 256 de Walker
Mastócitos
Inflamação
topic Carcinossarcoma
Carcinoma
Carcinoma 256 de Walker
Mastócitos
Inflamação
description Our objective was to evaluate the effect of the 256 Walker carcinossarcoma inoculation, as well as the time course of tumoral development, upon the acute inflammatory response in rats. Wistar rats, 180-220g, received intramuscular 106 tumor cells injections. At the end of 4, 7 or 10 days, wistar rats were separated into 4 groups, with 6 animals per group. The control group, were not inoculated with tumoral cells. Several parameters were evaluated: paw edema induced by carrageenan (Cg; 300μg/hind) or dextran (Dxt, 500μg/hind paw), myeloperoxidase activity (MPO), neutrophil migration to peritoneal cavity induced by carrageenan, cutaneous vascular permeability induced by bradykinin (2μg/site), serotonin (1μg/site), histamine (30μg/site), substance P (250ng/site), capsaicin (50μg/site) or 48/80 compound (1 μg/site) and mast cell degranulation induced by 48/80 compound. Paw edema was evaluated in the contra lateral hind paw of the tumor and measured at 0, 1, 2, 3 and 4h for Cg, and 0, 30’, 1, 2, 3 and 4h.for Dxt by plethysmometry. Neutrophil migration was induced by Cg injection in the contralateral hind paw or in the peritoneal cavity. After 4h, rats were sacrificed and the skin of the hind paw was harvested to measure neutrophil infiltration by MPO assay. Neutrophil migration induced by Cg was also evaluated in the peritoneal cavity, with the total e differential leucocytes counted. In order to measure cutaneous vascular permeability, immediately after intradermic stimulus injections (bradykinin, histamine, serotonin, substance P, capsaicin or 48/80 compound) Evans Blue dye was administrated (0,1mL/100g of per animal) by endovenous route. After 30 min rats were sacrificed and the skin was harvested to evaluate Evans Blue extravasations by spectrofotometry. Mast cells degranulation was evaluated in the in mesentery incubated with 48/80 compound and colored with toluidine blue. Our results shows that, in animals inoculated with the carcinossarcoma, there was a significant inhibition in the Cg and Dxt- induced paw edema, with maximal effect at the 7th and 10th days. There were no differences in MPO activity and neither in the peritoneal neutrophil infiltration induced by Cg in rats inoculated with the carcinossarcoma when compares to normal animals. After 4 and 7 days of the tumor inoculation, we observed a significant inhibition of the vascular permeability induced only by bradikinin, serotonin and 48/80 compound.. In the 10th day after the carcinossarcoma inoculation, there was a significant inhibition of the vascular permeability induced by all inflammatory stimulus tested, when we compared animals not inoculated. Mast cell degranulation was decreased in the 4th, 7th and 10th days after carcinossarcoma inoculation. These results suggested that the tumor microenvironment decreased the acute inflammatory response probably due to a inhibition of the mast cell degranulation.
publishDate 2007
dc.date.none.fl_str_mv 2007
2012-03-07T11:38:06Z
2012-03-07T11:38:06Z
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.uri.fl_str_mv BARBOSA, A. L. dos R. Modificação da resposta inflamatória sistêmica em ratos inoculados com carcinossarcoma 256 de Walker : papel da degranulação mastocitária. 2007. 135 f. Dissertação (Mestrado em Farmacologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2007.
http://www.repositorio.ufc.br/handle/riufc/2205
identifier_str_mv BARBOSA, A. L. dos R. Modificação da resposta inflamatória sistêmica em ratos inoculados com carcinossarcoma 256 de Walker : papel da degranulação mastocitária. 2007. 135 f. Dissertação (Mestrado em Farmacologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2007.
url http://www.repositorio.ufc.br/handle/riufc/2205
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