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Pharmacological modulation of inflammation associated with inflammatory bowel disease : study in a model of chronic experimental colitis in rodent

Publication . Silva, Inês; Mateus, Vanessa Alexandra Pinho; Pinto, Rui Manuel Amaro

Inflammatory bowel disease is recognized as a group of chronic inflammatory disorders, localized in the gastrointestinal tract. This chronic disease become a global healthcare concern, with a rising incidence in newly industrialized countries, adversely impacting the quality of life for affected individuals. Inflammatory bowel disease does not have a cure known and existing therapies aim to induce and maintain remission in patients and alleviate the secondary effects of the disease. Indeed, the pharmacological approaches, commonly used, demonstrate significant toxicity, which highlights the need to investigate new possible treatments for the long-term management of inflammatory bowel disease. The objective of this work is to evaluate new pharmacological approaches for inflammatory bowel disease, such as erythropoietin, carbamoylated erythropoietin, topiramate, and hemin in a chronic trinitrobenzene sulfonic acid(TNBS)-induced colitis in mice. Experimental colitis was induced in female CD-1 mice through repeated rectal administration of TNBS over a weekly schedule, during 4 weeks. The colitic mice were subjected to two weeks of treatment with daily doses of erythropoietin, hemin, topiramate, and carbamoylated erythropoietin. Several parameters were evaluated, including physiological, biochemical, and histological. Data analysis was performed using one-way ANOVA followed by Tukey's post hoc test. The colitic mice exhibited moderate morbidity, along with changes in intestinal motility characterized by the presence of soft stools and diarrhea, as well as increased levels of fecal calprotectin, fecal hemoglobin, alkaline phosphatase, and tumor necrosis factor-alpha. All tested drugs demonstrated anti-inflammatory effect on the development of chronic experimental colitis, specially erythropoietin, and hemin, as evidenced by the improvements in all evaluated parameters, leading to a reduction in both the severity and extent of the disease while maintaining safety. In conclusion, the findings indicate that all the tested drugs attenuate the chronic inflammatory response associated with the TNBS-induced colitis model.

2024-05Doctoral thesis

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