Chronic Experimental Model of TNBS-Induced Colitis to Study Inflammatory Bowel Disease.

Abstract

Background: 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.