Efeitos da formulação mucoadesiva com extrato de Curcuma longa L. em animais portadores de mucosite intestinal induzida por 5-fluorouracil
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| Data de Publicação: | 2014 |
| Tipo de documento: | Dissertação |
| Idioma: | por |
| Título da fonte: | Repositório Institucional da UFG |
| dARK ID: | ark:/38995/001300000drnb |
| Texto Completo: | http://repositorio.bc.ufg.br/tede/handle/tede/3114 |
Resumo: | Introduction: Intestinal mucositis is a frequent limiting factor in antineoplastic therapy. There is no truly effective treatment targeted to cure this side effect. Curcuma longa L. has been reported to have antioxidant, antitumor and anti-inflammatory properties. Objective: This study aimed to evaluate the effects of a mucoadhesive formulation with Curcuma longa L. extract (MCL) in mice bearing intestinal mucositis induced by 5-FU. Methods: Swiss male adult mice (35-40g) were randomly allocated into three experimental groups of 5 animals each: control (mucoadhesive formulation 0.6mL/animal, via gavage, from day 1-6); exposed to 5-fluorouracil (5-FU 200mg/kg, i.p., in days 4-6); treated prophylactically and throughout mucositis with FMCL and exposed to 5-FU (MCL 15mg/kg, via gavage, from day 1-6, plus 5-FU 200mg/kg, i.p., in days 4-6). In the 7th day, animals were anesthetized by xylazine-ketamine followed by cervical dislocation. Duodenal samples, 10 cm after pyloric sphincter were removed to perform the essays. The parameters evaluated were: body weight assessment, morphometrics and histo-pathological analysis, apoptosis (p53/Bax, Bcl-2), cell proliferation (Ki-67), myelo-peroxidase (MPO) and malondialdehyde (MDA). Results: 5-FU induced intestinal mucositis characterized by villus shortening, crypt deepening, intense inflammatory infiltration, vacuolization and mucosal edema. Besides, 5-FU induced severe mice body mass reduction, apoptosis in cells of villus and crypts (p<0.001), increase in MPO activity and MDA formation (p<0.05), when compared to the control group. Treatment with MCL attenuated body mass loss, protected intestinal mucosa from villus shortening and crypt deepening, decrease MPO activity and MDA formation (p<0.05). In this group of animals was also observed high expression of the cell proliferation marker Ki-67 in epithelial cells lining of villus and crypts. Conclusion: Our data confirm the therapeutic potential of MCL for the treatment of intestinal mucositis in mice. Further studies are needed to assess this formulation potential for human use. |
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Valadares, Marize Camposhttp://lattes.cnpq.br/6157755243167018Martins, Manoela DominguesMarreto, Ricardo Neveshttp://lattes.cnpq.br/9106451112293396Santos Filho, Edvande Xavier dos2014-09-22T18:45:16Z2014-03-20Santos Filho, Edvande Xavier dos. Efeitos da formulação mucoadesiva com extrato de Curcuma longa L. em animais portadores de mucosite intestinal induzida por 5-fluorouracil. 2014. 90 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia.http://repositorio.bc.ufg.br/tede/handle/tede/3114ark:/38995/001300000drnbIntroduction: Intestinal mucositis is a frequent limiting factor in antineoplastic therapy. There is no truly effective treatment targeted to cure this side effect. Curcuma longa L. has been reported to have antioxidant, antitumor and anti-inflammatory properties. Objective: This study aimed to evaluate the effects of a mucoadhesive formulation with Curcuma longa L. extract (MCL) in mice bearing intestinal mucositis induced by 5-FU. Methods: Swiss male adult mice (35-40g) were randomly allocated into three experimental groups of 5 animals each: control (mucoadhesive formulation 0.6mL/animal, via gavage, from day 1-6); exposed to 5-fluorouracil (5-FU 200mg/kg, i.p., in days 4-6); treated prophylactically and throughout mucositis with FMCL and exposed to 5-FU (MCL 15mg/kg, via gavage, from day 1-6, plus 5-FU 200mg/kg, i.p., in days 4-6). In the 7th day, animals were anesthetized by xylazine-ketamine followed by cervical dislocation. Duodenal samples, 10 cm after pyloric sphincter were removed to perform the essays. The parameters evaluated were: body weight assessment, morphometrics and histo-pathological analysis, apoptosis (p53/Bax, Bcl-2), cell proliferation (Ki-67), myelo-peroxidase (MPO) and malondialdehyde (MDA). Results: 5-FU induced intestinal mucositis characterized by villus shortening, crypt deepening, intense inflammatory infiltration, vacuolization and mucosal edema. Besides, 5-FU induced severe mice body mass reduction, apoptosis in cells of villus and crypts (p<0.001), increase in MPO activity and MDA formation (p<0.05), when compared to the control group. Treatment with MCL attenuated body mass loss, protected intestinal mucosa from villus shortening and crypt deepening, decrease MPO activity and MDA formation (p<0.05). In this group of animals was also observed high expression of the cell proliferation marker Ki-67 in epithelial cells lining of villus and crypts. Conclusion: Our data confirm the therapeutic potential of MCL for the treatment of intestinal mucositis in mice. Further studies are needed to assess this formulation potential for human use.Introdução: A mucosite intestinal é um dos efeitos adversos limitantes das terapias antineoplásicas. Não existe tratamento realmente efetivo direcionado a cura deste efeito colateral grave. A Curcuma longa L. tem sido proposta como candidata ao tratamento de várias doenças por possuir propriedades antioxidante, antitumoral e anti-inflamatória. Objetivo: Este estudo objetivou avaliar os efeitos da formulação mucoadesiva com extrato de Curcuma longa L. (FMCL) em animais portadores de mucosite intestinal induzida por 5-FU. Métodos: Camundongos Swiss adultos, machos (35-40g) foram aleatoriamente alocados em três grupos experimentais de 5 animais cada: [1] controle (formulação mucoadesiva 0.6mL/animal, via gavagem, do dia 1-6); [2] exposto ao 5-fluorouracil (5-FU 200mg/kg, i.p., dos dias 4-6), [3] tratado profilaticamente e ao curso da mucosite com FMCL e exposto ao 5-FU (FMCL 15mg/kg, via gavagem dos dias 1-6, mais 5-FU 200mg/kg, i.p., dos dias 4-6). No sétimo dia, os animais foram anestesiados por xilazina-ketamina seguido por deslocamento cervical. Amostras de duodeno, 10 cm após o esfíncter pilórico, foram coletadas para realização dos ensaios. Os parâmetros avaliados foram: avaliação de massa corporal, análise morfométrica e histopatológica, apoptose (p53/Bax; Bcl-2), proliferação celular (Ki-67), mieloperoxidase (MPO) e malondialdeído (MDA) Resultados: A administração de 5-FU induziu mucosite intestinal caracterizada por encurtamento das vilosidades, aprofundamento das criptas, intenso infiltrado infla-matório, vacuolização e edema na mucosa. Além disso, o 5-FU induziu grave redução de massa corporal nos camundongos e apoptose nas células das vilosida-des e criptas, quando comparado ao grupo controle (p<0,001). Foi observado ainda aumento na atividade de MPO e formação de MDA, quando comparado ao grupo controle (p<0,05). Por outro lado, o tratamento com a FMCL atenuou a perda de massa corporal dos animais com mucosite. Ademais, protegeu a mucosa intestinal da redução no tamanho das vilosidades e criptas induzidas pelo 5-FU. Neste grupo de animais foi observado ainda aumento na expressão do marcador de proliferação celular Ki-67 nas células epiteliais de revestimento das vilosidades e criptas intestinais. O tratamento também diminuiu significantemente a atividade de MPO e formação de MDA (p<0,05). Conclusão: Os dados confirmam o potencial terapêutico da FMCL no tratamento da mucosite intestinal em camundongos. Estudos adicionais são necessários para que esta formulação possa se tornar uma alternativa segura para uso em seres humanos.Submitted by Jaqueline Silva (jtas29@gmail.com) on 2014-09-22T17:08:11Z No. of bitstreams: 2 Santos Filho, Edvande-2014-dissertação.pdf: 3465269 bytes, checksum: fd50a85f70b6b596e0c5c4fb5fd18cb9 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5)Approved for entry into archive by Jaqueline Silva (jtas29@gmail.com) on 2014-09-22T18:45:16Z (GMT) No. of bitstreams: 2 Santos Filho, Edvande-2014-dissertação.pdf: 3465269 bytes, checksum: fd50a85f70b6b596e0c5c4fb5fd18cb9 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5)Made available in DSpace on 2014-09-22T18:45:16Z (GMT). No. of bitstreams: 2 Santos Filho, Edvande-2014-dissertação.pdf: 3465269 bytes, checksum: fd50a85f70b6b596e0c5c4fb5fd18cb9 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2014-03-20application/pdfhttp://repositorio.bc.ufg.br/tede/retrieve/8209/Santos%20Filho%2c%20Edvande-2014-disserta%c3%a7%c3%a3o.pdf.jpgporUniversidade Federal de GoiásPrograma de Pós-graduação em Ciências Farmacêuticas (FF)UFGBrasilFaculdade Farmácia - FF (RG)AGGARWAL, B. B.; KUMAR, A.; BHARTI, A. C. Anticancer potencial of curcumin: Preclinical and clinical studies. Anticancer Research. v. 23, p. 363–398, 2003. AGGARWAL, B. B.; YUAN, W.; LI, S.; GUPTA, S. C. Multitargeting by turmeric, the golden spice: From kitchen to clinic. Molecular Nutrition & Food Research. v. 00, p. 1–14, 2013. AHSAN, H.; PARVEEN, N.; KHAN, N. U.; HADI, S. M. Pro-oxidant, antioxidant and cleavage activities on DNA of curcumin and its derivatives demethoxycurcumin and bisdemethoxycurcumin. 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Initial chlorinating activity at neutral pH, compound II and III formation, and stability towards hypochlorous acid and high temperature. 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| dc.title.por.fl_str_mv |
Efeitos da formulação mucoadesiva com extrato de Curcuma longa L. em animais portadores de mucosite intestinal induzida por 5-fluorouracil |
| title |
Efeitos da formulação mucoadesiva com extrato de Curcuma longa L. em animais portadores de mucosite intestinal induzida por 5-fluorouracil |
| spellingShingle |
Efeitos da formulação mucoadesiva com extrato de Curcuma longa L. em animais portadores de mucosite intestinal induzida por 5-fluorouracil Santos Filho, Edvande Xavier dos Mucosite intestinal 5-fluorouracil Curcuma longa L. Formulação mucoadesiva Intestinal mucositis Mucoadhesive formulation CIENCIAS DA SAUDE::FARMACIA |
| title_short |
Efeitos da formulação mucoadesiva com extrato de Curcuma longa L. em animais portadores de mucosite intestinal induzida por 5-fluorouracil |
| title_full |
Efeitos da formulação mucoadesiva com extrato de Curcuma longa L. em animais portadores de mucosite intestinal induzida por 5-fluorouracil |
| title_fullStr |
Efeitos da formulação mucoadesiva com extrato de Curcuma longa L. em animais portadores de mucosite intestinal induzida por 5-fluorouracil |
| title_full_unstemmed |
Efeitos da formulação mucoadesiva com extrato de Curcuma longa L. em animais portadores de mucosite intestinal induzida por 5-fluorouracil |
| title_sort |
Efeitos da formulação mucoadesiva com extrato de Curcuma longa L. em animais portadores de mucosite intestinal induzida por 5-fluorouracil |
| author |
Santos Filho, Edvande Xavier dos |
| author_facet |
Santos Filho, Edvande Xavier dos |
| 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 |
Martins, Manoela Domingues |
| dc.contributor.referee2.fl_str_mv |
Marreto, Ricardo Neves |
| dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/9106451112293396 |
| dc.contributor.author.fl_str_mv |
Santos Filho, Edvande Xavier dos |
| contributor_str_mv |
Valadares, Marize Campos Martins, Manoela Domingues Marreto, Ricardo Neves |
| dc.subject.por.fl_str_mv |
Mucosite intestinal 5-fluorouracil Curcuma longa L. Formulação mucoadesiva |
| topic |
Mucosite intestinal 5-fluorouracil Curcuma longa L. Formulação mucoadesiva Intestinal mucositis Mucoadhesive formulation CIENCIAS DA SAUDE::FARMACIA |
| dc.subject.eng.fl_str_mv |
Intestinal mucositis Mucoadhesive formulation |
| dc.subject.cnpq.fl_str_mv |
CIENCIAS DA SAUDE::FARMACIA |
| description |
Introduction: Intestinal mucositis is a frequent limiting factor in antineoplastic therapy. There is no truly effective treatment targeted to cure this side effect. Curcuma longa L. has been reported to have antioxidant, antitumor and anti-inflammatory properties. Objective: This study aimed to evaluate the effects of a mucoadhesive formulation with Curcuma longa L. extract (MCL) in mice bearing intestinal mucositis induced by 5-FU. Methods: Swiss male adult mice (35-40g) were randomly allocated into three experimental groups of 5 animals each: control (mucoadhesive formulation 0.6mL/animal, via gavage, from day 1-6); exposed to 5-fluorouracil (5-FU 200mg/kg, i.p., in days 4-6); treated prophylactically and throughout mucositis with FMCL and exposed to 5-FU (MCL 15mg/kg, via gavage, from day 1-6, plus 5-FU 200mg/kg, i.p., in days 4-6). In the 7th day, animals were anesthetized by xylazine-ketamine followed by cervical dislocation. Duodenal samples, 10 cm after pyloric sphincter were removed to perform the essays. The parameters evaluated were: body weight assessment, morphometrics and histo-pathological analysis, apoptosis (p53/Bax, Bcl-2), cell proliferation (Ki-67), myelo-peroxidase (MPO) and malondialdehyde (MDA). Results: 5-FU induced intestinal mucositis characterized by villus shortening, crypt deepening, intense inflammatory infiltration, vacuolization and mucosal edema. Besides, 5-FU induced severe mice body mass reduction, apoptosis in cells of villus and crypts (p<0.001), increase in MPO activity and MDA formation (p<0.05), when compared to the control group. Treatment with MCL attenuated body mass loss, protected intestinal mucosa from villus shortening and crypt deepening, decrease MPO activity and MDA formation (p<0.05). In this group of animals was also observed high expression of the cell proliferation marker Ki-67 in epithelial cells lining of villus and crypts. Conclusion: Our data confirm the therapeutic potential of MCL for the treatment of intestinal mucositis in mice. Further studies are needed to assess this formulation potential for human use. |
| publishDate |
2014 |
| dc.date.accessioned.fl_str_mv |
2014-09-22T18:45:16Z |
| dc.date.issued.fl_str_mv |
2014-03-20 |
| 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 |
Santos Filho, Edvande Xavier dos. Efeitos da formulação mucoadesiva com extrato de Curcuma longa L. em animais portadores de mucosite intestinal induzida por 5-fluorouracil. 2014. 90 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia. |
| dc.identifier.uri.fl_str_mv |
http://repositorio.bc.ufg.br/tede/handle/tede/3114 |
| dc.identifier.dark.fl_str_mv |
ark:/38995/001300000drnb |
| identifier_str_mv |
Santos Filho, Edvande Xavier dos. Efeitos da formulação mucoadesiva com extrato de Curcuma longa L. em animais portadores de mucosite intestinal induzida por 5-fluorouracil. 2014. 90 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia. ark:/38995/001300000drnb |
| url |
http://repositorio.bc.ufg.br/tede/handle/tede/3114 |
| 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 |
| dc.relation.department.fl_str_mv |
6010281161524209375 |
| dc.relation.cnpq.fl_str_mv |
6997636413449754996 |
| dc.relation.references.por.fl_str_mv |
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