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- TNBS-induced colitis in rodents: preliminary results of a chronic modelPublication . Silva, Inês; Mateus, Vanessa; Pinto, RuiBackground: Inflammatory bowel disease (IBD) is a gastrointestinal disorder characterized by chronic inflammation of the intestinal epithelium. The symptoms of IBD depend on the intestinal affected segment and usually include diarrhea often with blood, colic abdominal pain, and fecal urgency. Beyond these, other unspecific symptoms may occur like fever, loss of appetite and weight, fatigue, and primary amenorrhea. Nowadays, used therapy in IBD consists of salicylates, corticosteroids, immunosuppressants, and biological therapy. These drugs aim to induce and/or maintain the patient in remission and ameliorate the disease’s secondary effects, rather than modifying or reversing the underlying pathogenic mechanism. Aim: Development of an animal model of trinitrobenzene sulfonic acid (TNBS)-induced chronic colitis in order to evaluate the influence of new drugs in the IBD.
- Chemically induced colitis-associated cancer models in rodents for pharmacological modulation: a systematic reviewPublication . Modesto, Rita; Estarreja, João; Silva, Inês; Rocha, João; Pinto, Rui; Mateus, VanessaAnimal models for colitis-associated colorectal cancer (CACC) represent an important tool to explore the mechanistic basis of cancer-related inflammation, providing important evidence that several inflammatory mediators play specific roles in the initiation and perpetuation of colitis and CACC. Although several original articles have been published describing the CACC model in rodents, there is no consensus about the induction method. This review aims to identify, summarize, compare, and discuss the chemical methods for the induction of CACC through the PRISMA methodology. Methods: We searched MEDLINE via the Pubmed platform for studies published through March 2021, using a highly sensitive search expression. The inclusion criteria were only original articles, articles where a chemically-induced animal model of CACC is described, preclinical studies in vivo with rodents, and articles published in English. Results: Chemically inducible models typically begin with the administration of a carcinogenic compound (as azoxymethane (AOM) or 1,2-dimethylhydrazine (DMH)), and inflammation is caused by repeated cycles of colitis-inducing agents (such as 2,4,6-trinitrobenzenesulfonic acid (TNBS) or dextran sulfate sodium (DSS)). The strains mostly used are C57BL/6 and Balb/c with 5–6 weeks. To characterize the preclinical model, the parameters more used include body weight, stool consistency, and morbidity, inflammatory biomarkers such as tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β, angiogenesis markers such as proliferating cell nuclear antigen (PCNA), a marker of proliferation Ki-67, and caspase 3, the presence of ulcers, thickness or hyperemia in the colon, and histological evaluation of inflammation. Conclusion: The AOM administration seems to be important to the CACC induction method since the carcinogenic effect is achieved with just one administration. DSS has been the more used inflammatory agent; however, the TNBS contribution should be more studied, since it allows a reliable, robust, and highly reproducible animal model of intestinal inflammation.
- Effect of Cynara cardunculus L. var. altilis (DC) in inflammatory bowel diseasePublication . Mateus, Vanessa; Estarreja, João; Silva, Inês; Barracosa, Paulo; Teixeira-Lemos, Edite; Pinto, RuiBackground: Cynara cardunculus L. var. altilis (DC) is a plant generally associated as an ingredient in the Mediterranean diet. The polyphenols present in this plant provide pharmacological and nutritional properties. C. cardunculus L. has been used throughout animal studies, which demonstrated an anti-inflammatory effect. Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract. Since there is not a known cure, the research of new possible pharmacological approaches is essential. This study aims to evaluate the effect of an aqueous extract of C. cardunculus L. dry leaves in a 2,4,6-Trinitrobenzenesulfonic acid (TNBS)-induced colitis model. Methods: CD-1 mice with TNBS-induced colitis received an intraperitoneal (IP) administration of C. cardunculus L. once per day for 4 days. Results: The C. cardunculus L. demonstrated a beneficial effect in this experimental model of IBD with anti-inflammatory action through the reduction of tumor necrosis factor (TNF)-α levels. It also demonstrated a beneficial influence on the extra-intestinal manifestations related to IBD, with the absence of significant side effects of its use. Conclusions: The extract of C. cardunculus L. dry leaves can become an interesting tool for new possible pharmacological approaches in the management of IBD.
- Effect of aqueous extract of phenolic compounds obtained from red wine in experimental model of colitis in micePublication . Mateus, Vanessa; Estarreja, João; Silva, Inês; Gonçalves, Fernando; Teixeira-Lemos, Edite; Pinto, RuiBackground: Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder represented by Crohn’s disease and ulcerative colitis. Currently, there is no cure and pharmacological treatment aims to induce and maintain remission in patients. Because the therapy reveals relatively high toxicity, during a long-term utilization, it is essential to investigate new pharmacological approaches. Polyphenols, commonly present in red wine, have shown health-beneficial effects related to their antioxidant and anti-inflammatory effects through the inhibition of NF-kB activation, COX-2, and iNOS induction. In this sense, it would be interesting to study their effects in an IBD context. Therefore, this study aims to evaluate the effects of an aqueous extract of phenolic compounds in a 2,4,6-Trinitrobenzenesulfonic acid (TNBS)-induced model of colitis. Method: Experimental colitis was induced in mice through an intrarectal administration of TNBS and then the mice were treated with an aqueous extract of phenolic compounds intraperitoneally for four days. Results and Discussion: The extract demonstrated an anti-inflammatory effect, reduced TNF-α levels in the colon, and had a beneficial effect on the extraintestinal manifestations related to IBD, without any significant side effects. The extract of phenolic compounds demonstrated to be a valuable object of study for the management of IBD in the future.