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Previous issue date: 2013-03-15 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Ulcerative colitis comprising an inflammatory bowel disease, whose most severe consequence is the development of intestinal neoplasia. The drugs currently used to treat the disease trigger a variety of serious adverse effects and are not effective in many cases. Recent studies demonstrated the effectiveness of natural products for the treatment of inflammatory processes. Seaweed extracts and their purified products have shown protective effects in models of inflammation and the association of traditional therapies with probiotics has significantly improved the clinical symptoms of ulcerative colitis. Therefore, the aims of this study include evaluating the potential effects of the use of probiotic strain Enterococcus faecium 32 (Ef32), the methanolic extract of the green seaweed Caulerpa mexicana (M.E.) and their concomitant administration in a murine model of colitis induced by dextran sodium sulfate (DSS). Accordingly, C57BL /6 mice were pretreated orally with Ef32 (109 CFU/ml) for seven days. In the seven days following, the colitis was induced by administration of 3% DSS (w/v) diluted in the animals drinking water. During this period, animals were treated daily with Ef32 and the M.E. (2.0 mg/kg) every other day by intravenous route. The development of colitis was monitored by the disease activity index (DAI), which takes into account the loss of body weight, consistency and presence of blood in stools. After euthanasia, the colon was removed, its length measured and tissue samples were destined for histological analysis and culture for cytokine quantification. The levels of cytokines in the culture supernatant of the colon were measured by ELISA. The treatments with the probiotic Ef32 or the M.E. alone or the combination of these two substances provoked significant improvement as to weight loss and DAI, and prevented the shortening of the colon in response to DSS. The isolated treatments triggered a slight improvement in intestinal mucosal tissue damage. However, their combination was able to completely repair the injury triggered by DSS. The association was also able to reduce the levels of all the cytokines analyzed (IFN-γ, IL-4, IL-6, IL-12, IL-17A and TNF-α). On the other hand, the treatment with Ef32 did not interfere with the levels of TNF-α, whereas treatment with M.E. did not alter the levels of IL-6. Moreover, the treatment with Ef32 not interferes in TNF-α levels, whereas treatment with M.E. did not alter the levels of IL-6. Therefore, the potential probiotic Ef32 and M.E. and especially when these samples were associated proved promising alternatives in the treatment of ulcerative colitis as demonstrated in an experimental model because of its beneficial effects on morphological and clinical parameters, and by reducing the production of proinflammatory cytokines of Th1, Th2 and Th17 / A colite ulcerativa compreende uma doen?a inflamat?ria intestinal, cuja consequ?ncia mais severa ? o desenvolvimento de neoplasia intestinal. Os medicamentos atualmente utilizados para o tratamento da doen?a desencadeiam uma variedade de efeitos adversos s?rios e n?o s?o eficazes em muitos casos. Estudos recentes apontaram para a efic?cia de produtos naturais no tratamento de processos inflamat?rios. Extratos de algas marinhas e seus produtos purificados t?m mostrado efeito protetor em modelos de inflama??o e a associa??o de terapias tradicionais com probi?ticos tem melhorado significativamente o quadro cl?nico da colite ulcerativa. Sendo assim, os objetivos do presente estudo inclu?ram avaliar os efeitos do uso da potencial cepa probi?tica Enterococcus faecium 32 (Ef32), do extrato metan?lico da alga marinha verde Caulerpa mexicana (E.M.) e da administra??o conjunta no modelo murino de colite induzida por dextrana sulfato de s?dio (DSS). Nesse sentido, camundongos C57BL/6 machos foram pr?-tratados oralmente com Ef32 (109 UFC/ml) durante sete dias. Nos sete dias seguintes, a colite experimental foi induzida atrav?s da administra??o DSS 3% (p/v) dilu?da na ?gua de beber dos animais. Neste per?odo, os animais foram tratados com Ef32 diariamente e com o E.M. (2,0 mg/kg) em dias alternados pela rota intravenosa. O desenvolvimento de colite foi monitorado atrav?s do ?ndice de atividade da doen?a (IAD), que leva em considera??o a perda de peso corporal, consist?ncia e presen?a de sangue nas fezes. Ap?s eutan?sia dos animais, o c?lon foi removido e mensurado e amostras do tecido foram destinadas ? an?lise histol?gica e cultura para dosagem de citocinas. Os n?veis de citocinas no sobrenadante da cultura do c?lon foram mensurados por ELISA. Os tratamentos com o probi?tico Ef32 ou com o E.M. sozinhos ou com a associa??o dessas duas subst?ncias desencadearam significativa melhora quanto ? perda de peso corporal e IAD, e preveniram o encurtamento do c?lon em resposta ? DSS. Os tratamentos isolados desencadearam uma melhora discreta no dano tecidual da mucosa intestinal. No entanto, a combina??o deles foi capaz de reparar completamente a inj?ria desencadeada pelo DSS. A associa??o foi ainda capaz de reduzir os n?veis de todas as citocinas analisadas (IFN-γ, IL-4, IL-6, IL-12, IL-17A e TNF-α). Por outro lado, o tratamento com Ef32 n?o interferiu nos n?veis de TNF-α, enquanto que o tratamento com o E.M n?o alterou os n?veis de IL-6. Portanto, o potencial probi?tico Ef32 e o E.M. e especialmente quando essas subst?ncias foram associadas, mostraram-se alternativas promissoras no tratamento da colite ulcerativa, como demonstrado no modelo experimental em raz?o dos seus efeitos ben?ficos sobre par?metros cl?nicos e morfol?gicos, bem como pela redu??o da produ??o de citocinas pr?-inflamat?rias das respostas Th1, Th2 e Th17
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufrn.br:123456789/13095 |
| Date | 15 March 2013 |
| Creators | Silva, Hylarina Montenegro Diniz |
| Contributors | CPF:61689858400, http://lattes.cnpq.br/6501426772186111, Guedes, Paulo Marcos da Matta, CPF:02351506731, http://lattes.cnpq.br/5445410844075357, Nascimento, George Jo?o Ferreira do, CPF:03356322460, http://lattes.cnpq.br/9194162897414436, Souto, Janeusa Trindade de |
| Publisher | Universidade Federal do Rio Grande do Norte, Programa de P?s-Gradua??o em Ci?ncias Biol?gicas, UFRN, BR, Biodiversidade; Biologia Estrutural e Funcional. |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | application/pdf |
| Source | reponame:Repositório Institucional da UFRN, instname:Universidade Federal do Rio Grande do Norte, instacron:UFRN |
| Rights | info:eu-repo/semantics/openAccess |
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