Preclinical Study in Vivo for New Pharmacological Approaches in Inflammatory Bowel Disease: A Systematic Review of Chronic Model of TNBS-Induced Colitis

Abstract

The preclinical studies in vivo provide means of characterizing physiologic interactions when our understanding of such processes is insufficient to allow replacement with in vitro systems and play a pivotal role in the development of a novel therapeutic drug cure. Chemically induced colitis models are relatively easy and rapid to develop. The 2,4,6-trinitrobenzenesulfonic acid (TNBS) colitis model is one of the main models in the experimental studies of inflammatory bowel disease (IBD) since inflammation induced by TNBS mimics several features of Crohn’s disease. This review aims to summarize the existing literature and discuss different protocols for the induction of chronic model of TNBS-induced colitis. We searched MEDLINE via Pubmed platform for studies published through December 2018, using MeSH terms (Crohn Disease.kw) OR (Inflammatory Bowel Diseases.kw) OR (Colitis, Ulcerative.kw) AND (trinitrobenzenesulfonic acid.kw) AND (disease models, animal.kw) AND (mice.all). The inclusion criteria were original articles, preclinical studies in vivo using mice, chronic model of colitis, and TNBS as the inducer of colitis and articles published in English. Chronic TNBS-induced colitis is made with multiple TNBS intrarectal administrations in an average dose of 1.2 mg using a volume lower than 150 μL in 50% ethanol. The strains mostly used are Balb/c and C57BL/6 with 5–6 weeks. To characterize the preclinical model the parameters more used include body weight, stool consistency and morbidity, inflammatory biomarkers like interferon (IFN)-γ, myeloperoxidase (MPO), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10, presence of ulcers, thickness or hyperemia in the colon, and histological evaluation of the inflammation. Experimental chronic colitis is induced by multiple rectal instillations of TNBS increasing doses in ethanol using Balb/c and C57BL/6 mice.

The Anti-Inflammatory Immune Response in Early Trichinella spiralis Intestinal Infection Depends on Serine Protease Inhibitor–Mediated Alternative Activation of Macrophages

“…In previous studies, the reversal effect on the pathological process in colitis model has been confirmed through injection of helminth-derived secretory proteins or adoptive transfer of helminth-induced macrophages (66)(67)(68). As a rapid and highly reproducible animal model, the TNBS-induced IBD model is characterized by acute colitis and exhibits a condition similar to Crohn disease (69). In this model, alleviation of pathological inflammatory processes appeared after treatment with rTs-serpin or rTs-serpin-treated BMDMs and was associated with a significant upregulation of anti-inflammatory cytokines, which supported the anti-inflammatory and regulatory effects of rTs-serpin identified previously.…”

Mycobacterial Hsp65 antigen delivered by invasive Lactococcus lactis reduces intestinal inflammation and fibrosis in TNBS-induced chronic colitis model

“…In addition, at week 8 in the experimental schedule, when the administrations of intrarectal TNBS were completed, all the animals belonging to these three groups exhibited some recovery, and their body weights were nearly equal to that of the C− group. These results might be explained by the decreased ability to maintain TNBS-induced colitis in mice older than 8 weeks 26 .…”

Effects of different treatment of faecal microbiota transplantation techniques on ulcerative colitis in rats

“…The rats were anaesthetised with 3% pentobarbital sodium (0.15 mL/100 g). A rubber infusion tube was then inserted 8 cm into the upper anus of each rat and injected with 5% TNBS at 100 mg/kg (dissolved in 50% ethanol, total volume of 1 mL) (34,35). To prevent uid leakage after colonic infusion and ensure the induction of colitis, the rats were placed in the Trendlenburg position with their head down for 1 min (36).…”