Efeitos da formulação mucoadesiva de Bidens pilosa L. (Asteraceae) e Curcuma longa L. (Zingiberaceae) no tratamento da mucosite intestinal

Detalhes bibliográficos
Autor(a) principal: Bastos, Carla Caroline Cunha
Data de Publicação: 2014
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UFG
Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/4114
Resumo: Intestinal mucositis is a limiting factor in anticancer therapies by causing gastrointestinal cell destruction reaching the majority of patients undergoing chemotherapy/radiotherapy and is often responsible for treatment discontinuation. Although several studies have already been conducted to treat this disease, there are still no universally accepted and standardized protocols of treatment. Plant species with anti-inflammatory and antioxidant properties have been considered for the treatment of mucositis, among them Bidens pilosa L. (BP) (Asteraceae) and Curcuma longa L. (CL) (Zingiberaceae). In this study, the effects of a formulation containing plant extracts of Bidens pilosa L. (BP) and Curcuma longa L. (CL), both with pharmaceutical technology of mucoadhesion in mice intestinal mucositis induced by 5-fluoruoacil (5-FU) were studied. This formulation was administered orally (gavage) for 6 days in each group of mice at doses of 75mg/kg + BP 3.75 mg / kg CL 100 mg / kg BP + 7.5 mg / kg or 125 mg CL / BP kg + 15 mg / kg CL. The treatment with the formulations occurred during six days, and in parallel with mucositis induction was performed with 5-FU (200 mg / kg, intraperitoneally) from day 4 to day 6. On day 7, the mice were euthanized and the duodenal portion of the intestine of each animal was extracted to perform the histomorphometry technique. From this analysis, the dose of 125 mg/kg mucoadhesive formulation showed best effectiveness results and was then chosen for the realization of the other tests: histopathology analysis, expression of Bax, Bcl-2, p53 and Ki-67 analysis via immunohistochemistry technique; analysis of the activity of myeloperoxidase (MPO) enzyme, and determination of malondialdehyde (MDA) levels. Furthermore, analysis of weight change and hematologic parameters were performed. To prove safety of the formulation, an oral toxicity test of mucoadhesive formulation, and effect evaluation of the plant extracts on the animals’intestine not submitted to mucositis were performed. The mucoadhesive formulation was able to assuage the histopathological damage caused by 5-FU; reduced weight loss, reduced levels of MPO and MDA; stimulated cell proliferation by increasing the expression of Ki-67; besides decreasing apoptosis observed by analyzing the expression of Bax and Bcl-2. The formulation at a dose of 2000mg/kg showed no signs of toxicity. It can be concluded that the formulation under study exerts preventive and/or therapeutic effects to intestinal mucositis with potential to be used with associated to anticancer treatment.
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spelling Valadares, Marize Camposhttp://lattes.cnpq.br/6157755243167018Valadares, Marize CamposCosta, Nádia do LagoSacono, Nancy Tomokohttp://lattes.cnpq.br/6737996666565849Bastos, Carla Caroline Cunha2015-02-05T14:20:06Z2014-04-11BASTOS, Carla Caroline Cunha. Efeitos da formulação mucoadesiva de Bidens pilosa L. (Asteraceae) e Curcuma longa L. (Zingiberaceae) no tratamento da mucosite intestinal. 2014. 79 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia, 2014.http://repositorio.bc.ufg.br/tede/handle/tede/4114Intestinal mucositis is a limiting factor in anticancer therapies by causing gastrointestinal cell destruction reaching the majority of patients undergoing chemotherapy/radiotherapy and is often responsible for treatment discontinuation. Although several studies have already been conducted to treat this disease, there are still no universally accepted and standardized protocols of treatment. Plant species with anti-inflammatory and antioxidant properties have been considered for the treatment of mucositis, among them Bidens pilosa L. (BP) (Asteraceae) and Curcuma longa L. (CL) (Zingiberaceae). In this study, the effects of a formulation containing plant extracts of Bidens pilosa L. (BP) and Curcuma longa L. (CL), both with pharmaceutical technology of mucoadhesion in mice intestinal mucositis induced by 5-fluoruoacil (5-FU) were studied. This formulation was administered orally (gavage) for 6 days in each group of mice at doses of 75mg/kg + BP 3.75 mg / kg CL 100 mg / kg BP + 7.5 mg / kg or 125 mg CL / BP kg + 15 mg / kg CL. The treatment with the formulations occurred during six days, and in parallel with mucositis induction was performed with 5-FU (200 mg / kg, intraperitoneally) from day 4 to day 6. On day 7, the mice were euthanized and the duodenal portion of the intestine of each animal was extracted to perform the histomorphometry technique. From this analysis, the dose of 125 mg/kg mucoadhesive formulation showed best effectiveness results and was then chosen for the realization of the other tests: histopathology analysis, expression of Bax, Bcl-2, p53 and Ki-67 analysis via immunohistochemistry technique; analysis of the activity of myeloperoxidase (MPO) enzyme, and determination of malondialdehyde (MDA) levels. Furthermore, analysis of weight change and hematologic parameters were performed. To prove safety of the formulation, an oral toxicity test of mucoadhesive formulation, and effect evaluation of the plant extracts on the animals’intestine not submitted to mucositis were performed. The mucoadhesive formulation was able to assuage the histopathological damage caused by 5-FU; reduced weight loss, reduced levels of MPO and MDA; stimulated cell proliferation by increasing the expression of Ki-67; besides decreasing apoptosis observed by analyzing the expression of Bax and Bcl-2. The formulation at a dose of 2000mg/kg showed no signs of toxicity. It can be concluded that the formulation under study exerts preventive and/or therapeutic effects to intestinal mucositis with potential to be used with associated to anticancer treatment.A mucosite intestinal é um fator limitante nas terapias com antineoplásicos por ocasionar destruição celular gastrointestinal atingindo a maioria dos pacientes submetidos à quimioterapia/radioterapia sendo muitas vezes responsável pela interrupção do tratamento. Apesar de vários estudos já terem sido realizados para o tratamento/prevenção desta patologia, ainda não existe nenhum protocolo padronizado aceito universalmente e com eficácia comprovada. Espécies vegetais com propriedades anti-inflamatórias e antioxidantes tem sido consideradas para o tratamento da mucosite, dentre elas a Bidens pilosa L. (BP) (Asteraceae) e a Curcuma longa L. (CL) (Zingiberaceae). Assim, neste estudo, os efeitos de uma formulação contendo os extratos vegetais de Bidens pilosa (BP) e Curcuma longa (CL), aliada à tecnologia farmacêutica de mucoadesão, foram estudados em animais portadores de mucosite intestinal induzida por 5-fluorouracil (5-FU). Esta formulação foi administrada por via oral (gavagem) durante 6 dias em cada grupo de camundongos nas doses de 75mg/kg BP + 3,75 mg/kg CL, 100 mg/kg BP+ 7,5 mg/kg CL ou 125 mg/kg BP + 15 mg/kg CL. O tratamento com as formulações foi de seis dias, sendo que em paralelo foi realizada a indução da mucosite com o 5-FU (200 mg/kg, intraperitonealmente) do 4º ao 6º dia. No 7º dia, os camundongos foram eutanasiados e a porção duodenal do intestino de cada animal foi extraída para realização da técnica de histomorfometria. A partir dessa análise, a dose de 125 mg/kg da formulação mucoadesiva obteve melhores resultados e foi escolhida então para a realização dos demais testes: análise histopatológica; análise da expressão de Bax, Bcl-2, p53 e Ki-67 pela técnica de imunohistoquímica; avaliação da atividade da enzima mieloperoxidase (MPO); e determinação dos níveis de malondialdeído (MDA). Além disso, foi realizada a análise de variação ponderal e a análise hematológica. Para comprovação da segurança da formulação estudada, foi realizado um teste de toxidade oral aguda da formulação mucoadesiva, e avaliação do efeito dos extratos vegetais sobre o intestino dos animais não submetidos à mucosite intestinal. A formulação mucoadesiva foi capaz de amenizar os danos histopatológicos causados pelo 5-FU; reduziu a perda de peso corporal, reduziu os níveis de MPO e MDA; estimulou proliferação celular verificada através do aumento da expressão de Ki-67; além de diminuir a apoptose observada através da análise da expressão de Bax e Bcl-2. A formulação na dose de 2000mg/kg não apresentou sinais de toxicidade. Pode-se concluir que a formulação em estudo exerce efeitos preventivos e/ou terapêuticos frente à mucosite intestinal com potencial para ser utilizada associada ao tratamento anticâncer.Submitted by Cássia Santos (cassia.bcufg@gmail.com) on 2015-02-04T10:49:57Z No. of bitstreams: 2 Dissertação - Carla Caroline Cunha Bastos - 2014.pdf: 2798020 bytes, checksum: 01f91c35952b2cac65bd16b118d8967a (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5)Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2015-02-05T14:20:06Z (GMT) No. of bitstreams: 2 Dissertação - Carla Caroline Cunha Bastos - 2014.pdf: 2798020 bytes, checksum: 01f91c35952b2cac65bd16b118d8967a (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5)Made available in DSpace on 2015-02-05T14:20:06Z (GMT). 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(Zingiberaceae) no tratamento da mucosite intestinalEffects of mucoadhesisee formulation of Bidens pilasa L. 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dc.title.eng.fl_str_mv Efeitos da formulação mucoadesiva de Bidens pilosa L. (Asteraceae) e Curcuma longa L. (Zingiberaceae) no tratamento da mucosite intestinal
dc.title.alternative.eng.fl_str_mv Effects of mucoadhesisee formulation of Bidens pilasa L. (Asteraceae) and Curcuma longa (Zingiberaceae) for treating intestitnal mucositis
title Efeitos da formulação mucoadesiva de Bidens pilosa L. (Asteraceae) e Curcuma longa L. (Zingiberaceae) no tratamento da mucosite intestinal
spellingShingle Efeitos da formulação mucoadesiva de Bidens pilosa L. (Asteraceae) e Curcuma longa L. (Zingiberaceae) no tratamento da mucosite intestinal
Bastos, Carla Caroline Cunha
Mucosite intestinal
Bidens pilosa L
Curcuma longa L
Intestinal mucositis
Bidens pilosa L
Curcuma longa L
Mucoadhesion
FARMACOLOGIA::FARMACOLOGIA CLINICA
title_short Efeitos da formulação mucoadesiva de Bidens pilosa L. (Asteraceae) e Curcuma longa L. (Zingiberaceae) no tratamento da mucosite intestinal
title_full Efeitos da formulação mucoadesiva de Bidens pilosa L. (Asteraceae) e Curcuma longa L. (Zingiberaceae) no tratamento da mucosite intestinal
title_fullStr Efeitos da formulação mucoadesiva de Bidens pilosa L. (Asteraceae) e Curcuma longa L. (Zingiberaceae) no tratamento da mucosite intestinal
title_full_unstemmed Efeitos da formulação mucoadesiva de Bidens pilosa L. (Asteraceae) e Curcuma longa L. (Zingiberaceae) no tratamento da mucosite intestinal
title_sort Efeitos da formulação mucoadesiva de Bidens pilosa L. (Asteraceae) e Curcuma longa L. (Zingiberaceae) no tratamento da mucosite intestinal
author Bastos, Carla Caroline Cunha
author_facet Bastos, Carla Caroline Cunha
author_role author
dc.contributor.advisor1.fl_str_mv Valadares, Marize Campos
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/6157755243167018
dc.contributor.referee1.fl_str_mv Valadares, Marize Campos
dc.contributor.referee2.fl_str_mv Costa, Nádia do Lago
dc.contributor.referee3.fl_str_mv Sacono, Nancy Tomoko
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/6737996666565849
dc.contributor.author.fl_str_mv Bastos, Carla Caroline Cunha
contributor_str_mv Valadares, Marize Campos
Valadares, Marize Campos
Costa, Nádia do Lago
Sacono, Nancy Tomoko
dc.subject.por.fl_str_mv Mucosite intestinal
Bidens pilosa L
Curcuma longa L
topic Mucosite intestinal
Bidens pilosa L
Curcuma longa L
Intestinal mucositis
Bidens pilosa L
Curcuma longa L
Mucoadhesion
FARMACOLOGIA::FARMACOLOGIA CLINICA
dc.subject.eng.fl_str_mv Intestinal mucositis
Bidens pilosa L
Curcuma longa L
Mucoadhesion
dc.subject.cnpq.fl_str_mv FARMACOLOGIA::FARMACOLOGIA CLINICA
description Intestinal mucositis is a limiting factor in anticancer therapies by causing gastrointestinal cell destruction reaching the majority of patients undergoing chemotherapy/radiotherapy and is often responsible for treatment discontinuation. Although several studies have already been conducted to treat this disease, there are still no universally accepted and standardized protocols of treatment. Plant species with anti-inflammatory and antioxidant properties have been considered for the treatment of mucositis, among them Bidens pilosa L. (BP) (Asteraceae) and Curcuma longa L. (CL) (Zingiberaceae). In this study, the effects of a formulation containing plant extracts of Bidens pilosa L. (BP) and Curcuma longa L. (CL), both with pharmaceutical technology of mucoadhesion in mice intestinal mucositis induced by 5-fluoruoacil (5-FU) were studied. This formulation was administered orally (gavage) for 6 days in each group of mice at doses of 75mg/kg + BP 3.75 mg / kg CL 100 mg / kg BP + 7.5 mg / kg or 125 mg CL / BP kg + 15 mg / kg CL. The treatment with the formulations occurred during six days, and in parallel with mucositis induction was performed with 5-FU (200 mg / kg, intraperitoneally) from day 4 to day 6. On day 7, the mice were euthanized and the duodenal portion of the intestine of each animal was extracted to perform the histomorphometry technique. From this analysis, the dose of 125 mg/kg mucoadhesive formulation showed best effectiveness results and was then chosen for the realization of the other tests: histopathology analysis, expression of Bax, Bcl-2, p53 and Ki-67 analysis via immunohistochemistry technique; analysis of the activity of myeloperoxidase (MPO) enzyme, and determination of malondialdehyde (MDA) levels. Furthermore, analysis of weight change and hematologic parameters were performed. To prove safety of the formulation, an oral toxicity test of mucoadhesive formulation, and effect evaluation of the plant extracts on the animals’intestine not submitted to mucositis were performed. The mucoadhesive formulation was able to assuage the histopathological damage caused by 5-FU; reduced weight loss, reduced levels of MPO and MDA; stimulated cell proliferation by increasing the expression of Ki-67; besides decreasing apoptosis observed by analyzing the expression of Bax and Bcl-2. The formulation at a dose of 2000mg/kg showed no signs of toxicity. It can be concluded that the formulation under study exerts preventive and/or therapeutic effects to intestinal mucositis with potential to be used with associated to anticancer treatment.
publishDate 2014
dc.date.issued.fl_str_mv 2014-04-11
dc.date.accessioned.fl_str_mv 2015-02-05T14:20:06Z
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 BASTOS, Carla Caroline Cunha. Efeitos da formulação mucoadesiva de Bidens pilosa L. (Asteraceae) e Curcuma longa L. (Zingiberaceae) no tratamento da mucosite intestinal. 2014. 79 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia, 2014.
dc.identifier.uri.fl_str_mv http://repositorio.bc.ufg.br/tede/handle/tede/4114
identifier_str_mv BASTOS, Carla Caroline Cunha. Efeitos da formulação mucoadesiva de Bidens pilosa L. (Asteraceae) e Curcuma longa L. (Zingiberaceae) no tratamento da mucosite intestinal. 2014. 79 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia, 2014.
url http://repositorio.bc.ufg.br/tede/handle/tede/4114
dc.language.iso.fl_str_mv por
language por
dc.relation.program.fl_str_mv 824936988196152412
dc.relation.confidence.fl_str_mv 600
600
600
600
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