Abstracts Biological Sciences

Pharmacological modulation of inflammation associated with inflammatory bowel disease : - study in an animal model

by Vanessa Alexandra Mateus

Tese de doutoramento, Farmácia (Farmacologia e Farmacoterapia), Universidade de Lisboa, Faculdade de Farmácia, 2016 Inflammatory bowel disease is a common gastro-intestinal disorder marked with chronic inflammation of intestinal epithelium, damaging mucosal tissue and manifests into several intestinal and extra-intestinal symptoms, mainly related to oxidative stress, inflammation and autoimmune type [Mowat, 2011; Pawar, 2011]. Currently used medical therapy of inflammatory bowel disease aim to induce and maintain the patient in remission and ameliorate the disease’s secondary effects, rather than modifying or reversing the underlying pathogenic mechanism [Engel, 2010; Pithadia, 2011]. Furthermore, their use may result in severe side effects and complications, such as an increased rate of malignancies or infectious diseases [Engel, 2010]. The main objective of the study is to evaluate the influence of a set of new drugs in inflammatory bowel disease, like erythropoietin, thiadiazolidinone-8 and hemin, through of an experimental colitis model induced by TNBS in rodents, contributing to facilitate a more effective and selective treatment than the currently known. Experimental colitis is induced by intracolonic administration of TNBS as described by Morris method [Morris, 1989]. The mice with colitis are treated with and without daily doses of erythropoietin, thiadiazolidinone-8 and hemin. The evaluated parameters are clinical symptoms/signs, colon length, fecal hemoglobin, ALP, urea, creatinine, ALT, MPO, TNF-α, IL-1β, IL-10 and histopathological score. TNBS-induced colitis was developed in 4 days, providing an acute intestinal inflammation model. These mice presented an increase of MPO, TNF-α, IL-1β and fecal hemoglobin. Erythropoietin treatment had a positive influence in the development of experimental colitis in all evaluated parameters, thus reducing its severity and extension. Thiadiazolidinone-8 derivate and hemin treatments had also a positive influence in the development of experimental colitis, but not in all evaluated parameters. All tested drugs significantly inhibit acute inflammatory response associated to the TNBS-induced colitis model. Escola Superior de Tecnologia da Saúde de Lisboa, Bolsa de Doutoramento concedida pela Caixa Geral de Depósitos - ESTeSL-IPL/CGD/2015 Advisors/Committee Members: Pinto, Rui Manuel Amaro, 1967-, Sepodes, Bruno Miguel Nogueira, 1977-.