Ulcerative colitis and Crohn's disease are a set of chronic, idiopathic, immunological and relapsing inflammatory disorders of the gastrointestinal tract referred to as inflammatory bowel disorder (IBD). Although the etiological factors involved in the perpetuation of IBD remain uncertain, development of various animal models provides new insights to unveil the onset and the progression of IBD. Various chemical-induced colitis models are widely used on laboratory scale. Furthermore, these models closely mimic morphological, histopathological and symptomatical features of human IBD. Among the chemical-induced colitis models, trinitrobenzene sulfonic acid (TNBS)-induced colitis, oxazolone induced-colitis and dextran sulphate sodium (DSS)-induced colitis models are most widely used. TNBS elicits Th-1 driven immune response, whereas oxazolone predominantly exhibits immune response of Th-2 phenotype. DSS-induced colitis model also induces changes in Th-1/Th-2 cytokine profile. The present review discusses the methodology and rationale of using various chemical-induced colitis models for evaluating the pathogenesis of IBD.

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A Review on Chemical-Induced Inflammatory Bowel Disease Models in Rodents

Glutathione peroxidase (GPX)-1 and gastrointestinal (GI) epithelium-specific GPX (GPX-GI), encoded byGpx1 and Gpx2, provide most GPX activity in GI epithelium. Although homozygous mice deficient in...

https://www.physiology.org/doi/pdf/10.1152/ajpgi.2001.281.3.G848

Mice with combined disruption of Gpx1 and Gpx2 genes have colitis.

Background—Reactive oxygen species contribute to tissue injury in inflammatory bowel disease (IBD). The tripeptide glutathione (GSH) is the most important intracellular antioxidant. Aims—To investigate constituent amino acid plasma levels and the GSH redox status in diVerent compartments in IBD with emphasis on intestinal GSH synthesis in Crohn’s disease. Methods—Precursor amino acid levels were analysed in plasma and intestinal mucosa. Reduced (rGSH) and oxidised glutathione (GSSG) were determined enzymatically in peripheral blood mononuclear cells (PBMC), red blood cells (RBC), muscle, and in non-inflamed and inflamed ileum mucosa. Mucosal enzyme activity of a-glutamylcysteine synthetase (aGCS) and a-glutamyl transferase (aGT) was analysed. Blood of healthy subjects and normal mucosa from a bowel segment resected for tumour growth were used as controls. Results—Abnormally low plasma cysteine and cystine levels were associated with inflammation in IBD (p<10 ‐4 ). Decreased rGSH levels were demonstrated in noninflamed mucosa (p<0.01) and inflamed mucosa (p=10 ‐6 ) in patients with IBD,

https://gut.bmj.com/content/gutjnl/42/4/485.full.pdf

Impairment of intestinal glutathione synthesis in patients with inflammatory bowel disease.

Summary

Background : Oral aloe vera gel is widely used by patients with inflammatory bowel disease and is under therapeutic evaluation for this condition.



Aim : To assess the effects of aloe vera in vitro on the production of reactive oxygen metabolites, eicosanoids and interleukin-8, all of which may be pathogenic in inflammatory bowel disease.



Methods : The anti-oxidant activity of aloe vera was assessed in two cell-free, radical-generating systems and by the chemiluminescence of incubated colorectal mucosal biopsies. Eicosanoid production by biopsies and interleukin-8 release by CaCo2 epithelial cells in the presence of aloe vera were measured by enzyme-linked immunosorbent assay.



Results : Aloe vera gel had a dose-dependent inhibitory effect on reactive oxygen metabolite production; 50% inhibition occurred at 1 in 1000 dilution in the phycoerythrin assay and at 1 in 10–50 dilution with biopsies. Aloe vera inhibited the production of prostaglandin E2 by 30% at 1 in 50 dilution (P = 0.03), but had no effect on thromboxane B2 production. The release of interleukin-8 by CaCo2 cells fell by 20% (P < 0.05) with aloe vera diluted at 1 in 100, but not at 1 in 10 or 1 in 1000 dilutions.



Conclusion : The anti-inflammatory actions of aloe vera gel in vitro provide support for the proposal that it may have a therapeutic effect in inflammatory bowel disease.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2036.2004.01874.x

Anti-inflammatory effects of aloe vera gel in human colorectal mucosa in vitro.

Intestinal redox biology and oxidative stress.

BACKGROUND: Reactive oxygen species may mediate tissue injury in inflammatory bowel disease. Aminosalicylates have antioxidant activity and the antioxidants, superoxide dismutase and allopurinol, are of reported benefit in inflammatory bowel disease. AIM: To develop a convenient technique for testing the antioxidant potential of standard and novel therapeutic agents for use in inflammatory bowel disease. METHODS: Amplified chemiluminescence was used to measure reactive oxygen species production by colonic biopsy specimens from rats with acetic acid induced colitis and to assess the in vitro effect of conventional antioxidants, standard therapies and proposed novel therapies for inflammatory bowel disease. RESULTS: The model was validated by demonstrating that the profile of effects on chemiluminescence of acetic acid induced colitis biopsy specimens given by conventional antioxidants (sodium azide, catalase, copper-zinc superoxide dismutase, dimethyl sulphoxide, N-acetylcysteine and ascorbate) and standard therapies (5-aminosalicylate and hydrocortisone) resembled that previously reported using biopsy specimens from ulcerative colitis. Human recombinant manganese superoxide dismutase did not alter chemiluminescence. Two novel compounds, LY231617 (10 mM) and amflutizole (20 mM), reduced chemiluminescence by 98% (n = 5, p = 0.009) and 88% (n = 5, p = 0.03), respectively. CONCLUSIONS: The similarity of the chemiluminescence responses of colonic biopsy specimens from acetic acid induced colitis and ulcerative colitis to a range of conventional antioxidants and standard treatments suggests that this model is a useful method for testing the antioxidant potential of new therapies for inflammatory bowel disease. The antioxidant actions of dimethyl sulphoxide, ascorbate, and the novel compounds, amflutizole and LY231617 in this model suggest that these agents merit further assessment in the treatment of inflammatory bowel disease.

https://gut.bmj.com/content/gutjnl/39/3/407.full.pdf

D. R. Blake

Papers

Evaluating the antioxidant potential of new treatments for inflammatory bowel disease using a rat model of colitis.

Evaluating theantioxidant potential ofnew treatments forinflammatory boweldisease using a ratmodelofcolitis