Anti-Inflammatory Effect of Topiramate in a Chronic Model of TNBS-Induced Colitis

Abstract

Inflammatory 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. These therapies, in the long term, 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 bodyweight, 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 the 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 the treatment of IBD in the future.

When less is more: Experimental Bishop–Koop technique for reduction in the use of laboratory animals for intestinal pathophysiological studies

“…Among experimental studies focused on gastrointestinal diseases found in the literature, IIRI-and 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats appears as a current model used by many authors and research groups around the world. [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] For this reason, we selected these two relevant pathologies to evaluate the experimental BK procedure in an intestinal injury scenario. IIRI was used for simulating a model of intestinal intussusception, strangulated hernia or intestinal transplantation.…”

“…[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] The same situation occurs in the field of experimental colitis, where old and recent scientific articles use one animal in each LI sample collection. [30][31][32][33][34][35][36][37] For the reasons mentioned above, it is a challenge to develop models that enable reducing the number of animals involved in these studies.…”

Efectos del precondicionamiento isquémico abdominal multiorgánico en modelos experimentales de isquemia-reperfusión

“…Este es un modelo experimental de interés de investigación en la actualidad entre las patología de intestino grueso utilizado por múltiples autores y grupos de investigación. (104)(105)(106)(107)(108)(109)(110)(111) Materiales y métodos: Se constituyeron tres grupos compuestos por ratas Sprague-Dawley hembras (peso 190 ± 2,6 gr). A las cuales se les realizó la técnica de BK en la porción distal del intestino grueso.…”