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Previous issue date: 2014-03-20 / 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. / 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.
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.bc.ufg.br:tede/3114 |
| Date | 20 March 2014 |
| Creators | Santos Filho, Edvande Xavier dos |
| Contributors | Valadares, Marize Campos, Martins, Manoela Domingues, Marreto, Ricardo Neves |
| Publisher | Universidade Federal de Goiás, Programa de Pós-graduação em Ciências Farmacêuticas (FF), UFG, Brasil, Faculdade Farmácia - FF (RG) |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | Portuguese |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da UFG, instname:Universidade Federal de Goiás, instacron:UFG |
| Rights | http://creativecommons.org/licenses/by-nc-nd/4.0/, info:eu-repo/semantics/openAccess |
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