Publicação
Preliminary study towards a novel chronic experimental model to study Inflammatory bowel disease
| Resumo: | Inflammatory bowel disease is a chronic inflammatory disorder of the epithelium of the intestinal tract caused by multiple factors and for which therapeutic options are limited. IBD is an idiopathic disease and the exact cause remains unknown. Patients with IBD have increased intestinal permeability, barrier disfunction of the epithelium and cumulative exposure to antigens leading to activation of the immune system, production of pro-inflammatory cytokines and reactive oxygen species resultant in intestinal mucosa lesions. The treatment currently used to IBD requires a long-term pharmacological approach based on the combination of drugs that have antiinflammatory activity and allows the inhibition of the initial events of inflammation, however consist only of symptomatic and palliative treatments and are unable to maintain remission of inflammation in the colon for long periods of time. Experimental models of IBD supply considerable information on the pathogenesis of this illness and represent an important tool in testing new strategies of treatment, since they mimic the features of the disease. The main aim of this project is to develop a preliminary study towards a novel chronic experimental model to study IBD in order to support a future new model of chronic induced colitis in rodents using TNBS. The experimental model with TNBS consists in the induction of intestinal inflammation by a chemical process through intracolonic administration of TNBS. The mice were evaluated taking into account parameters such as body weight, stool consistency, anus appearance and colon length and biochemical markers such as ALP, urea, creatinine, ALT, fecal hemoglobin, TNF-α, IL-10 and histopathological score. TNBS-induced chronic colitis was tested in 6 weeks, with weekly TNBS instillations, providing a chronic intestinal inflammation model. The TNBS groups showed a slight change in intestinal motility characterized by diarrhea, anus edema and moderate morbidity, while the control groups remained unchanged. These mice also showed a slight and progressive increase in body weight, a reduced colon length, and an increase in fecal hemoglobin concentration, which was maintained until the end of the experimental protocol. Colitic mice presented raised values of ALP, TNF-α and fecal hemoglobin after week 4 until the end of the experiment, and contrary to expected increase values of an antiinflammatory cytokine, IL-10. These results are consistent with the correct induction of experimental chronic colitis by TNBS. These preliminary data allow suggesting that TNBS-induced chronic colitis should be developed in 4 weeks, providing a chronic intestinal inflammation model. |
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| Autores principais: | Modesto, Rita Eusébio |
| Assunto: | Inflammatory bowel disease Crohn disease Ulcerative colitis TNBS induced colitis Animal model Teses de mestrado - 2019 |
| Ano: | 2019 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | Inflammatory bowel disease is a chronic inflammatory disorder of the epithelium of the intestinal tract caused by multiple factors and for which therapeutic options are limited. IBD is an idiopathic disease and the exact cause remains unknown. Patients with IBD have increased intestinal permeability, barrier disfunction of the epithelium and cumulative exposure to antigens leading to activation of the immune system, production of pro-inflammatory cytokines and reactive oxygen species resultant in intestinal mucosa lesions. The treatment currently used to IBD requires a long-term pharmacological approach based on the combination of drugs that have antiinflammatory activity and allows the inhibition of the initial events of inflammation, however consist only of symptomatic and palliative treatments and are unable to maintain remission of inflammation in the colon for long periods of time. Experimental models of IBD supply considerable information on the pathogenesis of this illness and represent an important tool in testing new strategies of treatment, since they mimic the features of the disease. The main aim of this project is to develop a preliminary study towards a novel chronic experimental model to study IBD in order to support a future new model of chronic induced colitis in rodents using TNBS. The experimental model with TNBS consists in the induction of intestinal inflammation by a chemical process through intracolonic administration of TNBS. The mice were evaluated taking into account parameters such as body weight, stool consistency, anus appearance and colon length and biochemical markers such as ALP, urea, creatinine, ALT, fecal hemoglobin, TNF-α, IL-10 and histopathological score. TNBS-induced chronic colitis was tested in 6 weeks, with weekly TNBS instillations, providing a chronic intestinal inflammation model. The TNBS groups showed a slight change in intestinal motility characterized by diarrhea, anus edema and moderate morbidity, while the control groups remained unchanged. These mice also showed a slight and progressive increase in body weight, a reduced colon length, and an increase in fecal hemoglobin concentration, which was maintained until the end of the experimental protocol. Colitic mice presented raised values of ALP, TNF-α and fecal hemoglobin after week 4 until the end of the experiment, and contrary to expected increase values of an antiinflammatory cytokine, IL-10. These results are consistent with the correct induction of experimental chronic colitis by TNBS. These preliminary data allow suggesting that TNBS-induced chronic colitis should be developed in 4 weeks, providing a chronic intestinal inflammation model. |
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