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- Preliminary results of an animal model validation of chronic experimental colitisPublication . Silva, Inês; Pinto, Rui; Mateus, VanessaInflammatory bowel disease (IBD): chronic inflammatory disease of the gastrointestinal (GI) tract characterized by recurrent ulceration. IBD prevalence exceeding 0,5% of the population in westernized countries. IBD manifests into several intestinal and extra-intestinal symptoms, mainly related to inflammation. IBD includes Crohn’s disease and Ulcerative colitis. Aim of the study: evaluate the efficacy of new drugs in IBD through an animal model of TNBS-induced chronic colitis.
- New pharmacological approach for inflammatory bowel diseasePublication . Silva, Inês; Pinto, Rui; Mateus, VanessaInflammatory bowel disease includes Crohn's disease and ulcerative colitis. Chronic inflammatory disease of the gastrointestinal (GI) tract is characterized by recurrent ulceration. IBD affects 7–10% of people worldwide, mainly of Caucasian descent. It manifests into several intestinal and extra-intestinal symptoms, mainly related to oxidative stress, inflammation, and autoimmune reaction. Aim of the study: evaluate the influence of a new pharmacological approach with erythropoietin in the establishment and development of inflammation associated with IBD, through of an experimental colitis model in rodents.
- 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.
- Hemin ameliorates the inflammatory activity in the inflammatory bowel disease: a non-clinical study in rodentsPublication . Silva, Inês; Correia, Rita; Pinto, Rui; Mateus, VanessaBackground: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract. Currently, there is no cure, and pharmacological treatment aims to induce and maintain remission in patients, so it is essential to investigate new possible treatments. Hemin is a heme-oxygenase inducer that can confer anti-inflammatory, cytoprotective, and antiapoptotic effects; therefore, it can be considered an asset for different gastrointestinal pathologies, namely for IBD. Aim: This experiment aims to evaluate the efficacy and safety of hemin, in a chronic 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model in rodents. Methods: The induction of chronic colitis consisted of five weekly intrarectal administrations of 1% TNBS. Then, the mice were treated daily with 5 mg/kg/day or 10 mg/kg/day of hemin, through intraperitoneal injections, for 14 days. Results: Hemin demonstrated an anti-inflammatory effect through the reduction in tumor necrosis factor (TNF)-α levels, fecal calprotectin, and fecal hemoglobin. It was also found to be safe in terms of extraintestinal manifestations since hemin did not promote renal and/or hepatic changes. Conclusions: Hemin could become an interesting tool for new possible pharmacological approaches in the management of IBD.
- Anti-inflammatory effect of topiramate in a chronic model of TNBS-induced colitisPublication . Silva, Inês; Mendes, Priscila; Guerra, Sofia; Pinto, Rui; Mateus, VanessaInflammatory bowel disease (IBD) is characterized by a chronic and relapsing inflammatory response in the gastrointestinal tract, resulting in severe symptoms such as abdominal pain, vomiting, diarrhea, bloody stools, and weight loss. Currently, there is no cure, and the pharmacological treatment includes drugs that induce and keep the patient in remission, not reversing the underlying pathogenic mechanism. In the long term, these therapies may cause various side effects and complications, which has increased the need to investigate new, more effective, and safer pharmacological approaches. In preclinical studies, topiramate has demonstrated a potential anti-inflammatory effect by inhibiting the production of several pro-inflammatory cytokines. This study aimed to investigate the effect of topiramate in a chronic TNBS-induced colitis model in rodents. Experimental colitis was induced by four intrarectal administrations of 1% TNBS in female CD-1 mice. Topiramate 10 and 20 mg were administered intraperitoneally for 14 days. Several parameters were evaluated, such as body weight, alkaline phosphatase (ALP), fecal hemoglobin, fecal calprotectin, tumor necrosis factor (TNF)-α, and interleukin (IL)-10. Topiramate reduces TNBS-induced colonic damage in a model of chronic experimental colitis and normalizes stool consistency and anus appearance. Additionally, topiramate significantly reduced the concentration of ALP, fecal hemoglobin, fecal calprotectin, TNF-α, and IL-10, demonstrating it to be a promising pharmacological approach for treating IBD in the future.
- Efficacy and safety of erythropoietin in a chronic model of inflammatory bowel diseasePublication . Silva, Inês; Estarreja, João; Pinto, Rui; Mateus, VanessaBackground: Inflammatory Bowel Disease (IBD) is recognized as a group of chronic inflammatory disorders, localized in the gastrointestinal tract, which does not have a cure known. Indeed, the pharmacological approaches, commonly used, demonstrate significant toxicity, which highlights the need of investigating new possible treatments. Erythropoietin (EPO) is clinically used in anemic patients, with chronic renal insufficiency, due to its erythropoietic effect. However, it has also been described other non-erythropoietic effects, such as an anti-inflammatory role. There is already preclinical evidence about its anti-inflammatory effect in the IBD context, namely in an acute model of colitis in mice. Therefore, it is relevant to ascertain its anti-inflammatory effect in a chronic model, but mainly its hematopoietic side effect, during chronic treatment. Aim: This experiment aims to evaluate the efficacy and safety of EPO treatment in a chronic 2,4,6-Trinitrobenzenesulfonic acid (TNBS)-induced colitis model in rodents. Methods: The induction of chronic colitis consisted of five weekly intrarectal administrations of 1% TNBS, and then mice were treated daily with 500 IU/Kg or 1000 IU/Kg of EPO, through intraperitoneal injections, for 14 days. Results: EPO demonstrated a significant anti-inflammatory effect, translated by a significant reduction of the concentration of tumor necrosis factor-α, fecal calprotectin, and fecal hemoglobin. Moreover, it has also been demonstrated to be safe, considering the cardiovascular system, in terms of extraintestinal manifestations, namely at renal and hepatic functions. Conclusions: EPO demonstrated to be a promising pharmacological approach to be considered in the management of IBD, being an interesting target for drug repositioning.
- TNBS-induced colitis in rodents: preliminary results of a chronic modelPublication . Silva, Inês; Solas, João; Sousa, Mariana; Modesto, Rita; Mateus, Vanessa; Pinto, RuiChronic inflammatory disease of the gastrointestinal (GI) tract characterized by recurrent ulceration. Treatment of inflammatory bowel disease induce and maintain the patient in remission However do not modify or reverse the underlying pathogenic mechanism. Nonclinical studies for emerging therapeutic strategies. Aim of the study: Evaluate the efficacy of new drugs in inflammatory bowel disease through an animal model of TNBS-induced chronic colitis.
- 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.
- Chronic experimental model of TNBS-induced colitis to study inflammatory bowel diseasePublication . Silva, Inês; Solas, João; Pinto, Rui; Mateus, VanessaBackground: Inflammatory bowel disease (IBD) is a world healthcare problem. In order to evaluate the effect of new pharmacological approaches for IBD, we aim to develop and validate chronic trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. Methods: Experimental colitis was induced by the rectal administration of multiple doses of TNBS in female CD-1 mice. The protocol was performed with six experimental groups, depending on the TNBS administration frequency, and two control groups (sham and ethanol groups). Results: The survival rate was 73.3% in the first three weeks and, from week 4 until the end of the experimental protocol, the mice’s survival remained unaltered at 70.9%. Fecal hemoglobin presented a progressive increase until week 4 (5.8 ± 0.3 µmol Hg/g feces, p < 0.0001) compared with the ethanol group, with no statistical differences to week 6. The highest level of tumor necrosis factor-α was observed on week 3; however, after week 4, a slight decrease in tumor necrosis factor-α concentration was verified, and the level was maintained until week 6 (71.3 ± 3.3 pg/mL and 72.7 ± 3.6 pg/mL, respectively). Conclusions: These findings allowed the verification of a stable pattern of clinical and inflammation signs after week 4, suggesting that the chronic model of TNBS-induced colitis develops in 4 weeks.
- 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.