Rutina reduz as alterações morfológicas no modelo experimental de mucosite intestinal induzida por 5-fluorouracil

Intestinal mucositis is an adverse effect commonly associated with 5-fluorouracil (5-FU), an antimetabolite chemotherapeutic agent used in cancer therapy. For rutin (RUT), a flavonoid extracted from Dimorphandra gardneriana, several pharmacological activities have been described, such as antioxidant...

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Detalles Bibliográficos
Autor: Fideles, Lázaro de Sousa
Tipo de recurso: tesis de maestría
Estado:Versión publicada
Fecha de publicación:2020
País:Brasil
Institución:Universidade Federal do Ceará (UFC)
Repositorio:Repositório Institucional da Universidade Federal do Ceará (UFC)
Idioma:portugués
OAI Identifier:oai:repositorio.ufc.br:riufc/54219
Acceso en línea:http://www.repositorio.ufc.br/handle/riufc/54219
Access Level:acceso abierto
Palabra clave:Antineoplásicos
Mucosite
Fluoruracila
Produtos Biológicos
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network_name_str Brasil
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dc.title.pt_BR.fl_str_mv Rutina reduz as alterações morfológicas no modelo experimental de mucosite intestinal induzida por 5-fluorouracil
title Rutina reduz as alterações morfológicas no modelo experimental de mucosite intestinal induzida por 5-fluorouracil
spellingShingle Rutina reduz as alterações morfológicas no modelo experimental de mucosite intestinal induzida por 5-fluorouracil
Fideles, Lázaro de Sousa
Antineoplásicos
Mucosite
Fluoruracila
Produtos Biológicos
title_short Rutina reduz as alterações morfológicas no modelo experimental de mucosite intestinal induzida por 5-fluorouracil
title_full Rutina reduz as alterações morfológicas no modelo experimental de mucosite intestinal induzida por 5-fluorouracil
title_fullStr Rutina reduz as alterações morfológicas no modelo experimental de mucosite intestinal induzida por 5-fluorouracil
title_full_unstemmed Rutina reduz as alterações morfológicas no modelo experimental de mucosite intestinal induzida por 5-fluorouracil
title_sort Rutina reduz as alterações morfológicas no modelo experimental de mucosite intestinal induzida por 5-fluorouracil
dc.creator.none.fl_str_mv Fideles, Lázaro de Sousa
author Fideles, Lázaro de Sousa
author_facet Fideles, Lázaro de Sousa
author_role author
dc.contributor.co-advisor.none.fl_str_mv Martins, Conceição da Silva
dc.contributor.advisor1.fl_str_mv Cerqueira, Gilberto Santos
contributor_str_mv Cerqueira, Gilberto Santos
dc.subject.por.fl_str_mv Antineoplásicos
Mucosite
Fluoruracila
Produtos Biológicos
topic Antineoplásicos
Mucosite
Fluoruracila
Produtos Biológicos
description Intestinal mucositis is an adverse effect commonly associated with 5-fluorouracil (5-FU), an antimetabolite chemotherapeutic agent used in cancer therapy. For rutin (RUT), a flavonoid extracted from Dimorphandra gardneriana, several pharmacological activities have been described, such as antioxidant and anti-inflammatory. In the present study, the objective was to evaluate the effect of RUT on experimental intestinal mucositis induced by 5-FU in Swiss mice. Swiss mice were randomly divided into groups: Saline, 5-FU, RUT-50 (50 mg / kg RUT), RUT-100 (100 mg / kg RUT), RUT-200 (200 mg / kg RUT), Celecoxib (CLX, 7.5 mg / kg of Celecoxib) and CLX + RUT-200 (CLX + 200 mg / kg of RUT). The weight of the mice was assessed daily. After mucositis induction (single administration of 450 mg / kg of 5-FU, intraperitoneally) and after 3 consecutive days of treatment, the animals were euthanized and segments of the small intestine were collected for histopathological and morphometric evaluation, malondialdehyde (MDA), myeloperoxidase (MPO), Glutathione (GSH), mast cell and goblet cell count, immunohistochemistry for cyclooxygenase 2 (COX-2). Molecular docking was also carried out for possible RUT sites of action. 5-FU induced intense weight loss and reduced villus height compared to the saline group. Treatment with RUT decreased the histopathological changes induced by 5-FU and decreased the level of oxidative stress, decreasing the levels of MDA and increasing the concentration of GSH. RUT attenuated the inflammatory process, decreasing MPO activity, intestinal mastocytosis and COX-2 expression. Our findings suggest that the flavonoid RUT reverses the morphofunctional changes induced by 5-FU and has as a possible mechanism of action the COX-2 pathway.
publishDate 2020
dc.date.accessioned.fl_str_mv 2020-09-23T11:30:50Z
dc.date.available.fl_str_mv 2020-09-23T11:30:50Z
dc.date.issued.fl_str_mv 2020-09-11
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.citation.fl_str_mv FIDELES, L. S. Rutina reduz as alterações morfológicas no modelo experimental de mucosite intestinal induzida por 5-fluorouracil. 2020. 84 f. Dissertação (Mestrado em Ciências Morfofuncionais) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2020.
dc.identifier.uri.fl_str_mv http://www.repositorio.ufc.br/handle/riufc/54219
identifier_str_mv FIDELES, L. S. Rutina reduz as alterações morfológicas no modelo experimental de mucosite intestinal induzida por 5-fluorouracil. 2020. 84 f. Dissertação (Mestrado em Ciências Morfofuncionais) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2020.
url http://www.repositorio.ufc.br/handle/riufc/54219
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:Repositório Institucional da Universidade Federal do Ceará (UFC)
instname:Universidade Federal do Ceará (UFC)
instacron:UFC
instname_str Universidade Federal do Ceará (UFC)
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institution UFC
reponame_str Repositório Institucional da Universidade Federal do Ceará (UFC)
collection Repositório Institucional da Universidade Federal do Ceará (UFC)
bitstream.url.fl_str_mv http://repositorio.ufc.br/bitstream/riufc/54219/1/2020_dis_lsfideles.pdf
http://repositorio.ufc.br/bitstream/riufc/54219/2/license.txt
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repository.name.fl_str_mv Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)
repository.mail.fl_str_mv bu@ufc.br || repositorio@ufc.br
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spelling Martins, Conceição da SilvaCerqueira, Gilberto Santos2020-09-23T11:30:50Z2020-09-23T11:30:50Z2020-09-11FIDELES, L. S. Rutina reduz as alterações morfológicas no modelo experimental de mucosite intestinal induzida por 5-fluorouracil. 2020. 84 f. Dissertação (Mestrado em Ciências Morfofuncionais) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2020.http://www.repositorio.ufc.br/handle/riufc/54219Intestinal mucositis is an adverse effect commonly associated with 5-fluorouracil (5-FU), an antimetabolite chemotherapeutic agent used in cancer therapy. For rutin (RUT), a flavonoid extracted from Dimorphandra gardneriana, several pharmacological activities have been described, such as antioxidant and anti-inflammatory. In the present study, the objective was to evaluate the effect of RUT on experimental intestinal mucositis induced by 5-FU in Swiss mice. Swiss mice were randomly divided into groups: Saline, 5-FU, RUT-50 (50 mg / kg RUT), RUT-100 (100 mg / kg RUT), RUT-200 (200 mg / kg RUT), Celecoxib (CLX, 7.5 mg / kg of Celecoxib) and CLX + RUT-200 (CLX + 200 mg / kg of RUT). The weight of the mice was assessed daily. After mucositis induction (single administration of 450 mg / kg of 5-FU, intraperitoneally) and after 3 consecutive days of treatment, the animals were euthanized and segments of the small intestine were collected for histopathological and morphometric evaluation, malondialdehyde (MDA), myeloperoxidase (MPO), Glutathione (GSH), mast cell and goblet cell count, immunohistochemistry for cyclooxygenase 2 (COX-2). Molecular docking was also carried out for possible RUT sites of action. 5-FU induced intense weight loss and reduced villus height compared to the saline group. Treatment with RUT decreased the histopathological changes induced by 5-FU and decreased the level of oxidative stress, decreasing the levels of MDA and increasing the concentration of GSH. RUT attenuated the inflammatory process, decreasing MPO activity, intestinal mastocytosis and COX-2 expression. Our findings suggest that the flavonoid RUT reverses the morphofunctional changes induced by 5-FU and has as a possible mechanism of action the COX-2 pathway.Mucosite intestinal é um efeito adverso comumente associado ao 5-fluorouracil (5-FU), um agente quimioterápico antimetabolito usado na terapêutica do câncer. Para a rutina (RUT), um flavonóide extraído de Dimorphandra gardneriana, várias atividades farmacológicas têm sido descritas, como antioxidante e anti-inflamatória. No presente estudo, objetivou-se avaliar o efeito do RUT na mucosite intestinal experimental induzida pelo 5-FU em camundongos Swiss. Os camundongos Swiss foram divididos aleatoriamente em grupos: Salina, 5-FU, RUT-50 (50 mg/kg de RUT), RUT-100 (100 mg/kg de RUT), RUT-200 (200 mg/kg de RUT), Celecoxibe (CLX, 7,5 mg/kg de Celecoxibe) e CLX + RUT-200 (CLX + 200 mg/kg de RUT). O peso dos camundongos foi avaliado diariamente. Após indução da mucosite (administração única de 450 mg/kg de 5-FU, via intraperitoneal) e decorrido os 3 dias consecutivos de tratamento, os animais foram eutanasiados e segmentos do intestino delgado foram coletados para avaliação histopatológica e morfométrica, malondialdeído (MDA), mieloperoxidase (MPO), Glutationa (GSH), contagem de mastócitos e células caliciformes, imunohistoquímica para ciclooxigenase 2 (COX-2). Realizou-se também a docagem molecular para os possíveis sítios de ação da RUT. O 5-FU induziu intensa perda de peso e redução na altura das vilosidades em comparação com o grupo salina. O tratamento com RUT diminuiu as alterações histopatológicas induzidas por 5-FU e diminuiu nível do estresse oxidativo, diminuindo os níveis de MDA e aumentando a concentração de GSH. RUT atenuou o processo inflamatório, diminuindo a atividade da MPO, mastocitose intestinal e expressão da COX-2. Nossos achados sugerem que o flavonóide RUT reverte as alterações morfofuncionais induzida pelo 5-FU e tenha como possível mecanismo de ação a via da COX-2.AntineoplásicosMucositeFluoruracilaProdutos BiológicosRutina reduz as alterações morfológicas no modelo experimental de mucosite intestinal induzida por 5-fluorouracilinfo: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/openAccessFideles, Lázaro de SousaORIGINAL2020_dis_lsfideles.pdf2020_dis_lsfideles.pdfapplication/pdf4345187http://repositorio.ufc.br/bitstream/riufc/54219/1/2020_dis_lsfideles.pdff3f7db368c69eb6b0c445693fd0bf98cMD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/54219/2/license.txt8a4605be74aa9ea9d79846c1fba20a33MD52riufc/542192020-09-23 08:30:50.456oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2020-09-23T11:30:50Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
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