Acid-induced Colitis In Mice Research Articles

Curcumin, the major component of food flavour turmeric, reduces mucosal injury in trinitrobenzene sulphonic acid-induced colitis.

1 Inflammmatory bowel disease (IBD) is characterized by oxidative and nitrosative stress, leucocyte infiltration and upregulation of proinflammatory cytokines. In this study, we have investigated the protective effects of curcumin, an anti-inflammatory and antioxidant food derivative, on 2,4,6- trinitrobenzene sulphonic acid-induced colitis in mice, a model for IBD. 2 Intestinal lesions (judged by macroscopic and histological score) were associated with neutrophil infiltration (measured as increase in myeloperoxidase activity in the mucosa), increased serine protease activity (may be involved in the degradation of colonic tissue) and high levels of malondialdehyde (an indicator of lipid peroxidation). 3 Dose-response studies revealed that pretreatment of mice with curcumin (50 mg kg(-1) daily i.g. for 10 days) significantly ameliorated the appearance of diarrhoea and the disruption of colonic architecture. Higher doses (100 and 300 mg kg(-1)) had comparable effects. 4 In curcumin-pretreated mice, there was a significant reduction in the degree of both neutrophil infiltration (measured as decrease in myeloperoxidase activity) and lipid peroxidation (measured as decrease in malondialdehyde activity) in the inflamed colon as well as decreased serine protease activity. 5 Curcumin also reduced the levels of nitric oxide (NO) and O(2)(-) associated with the favourable expression of Th1 and Th2 cytokines and inducible NO synthase. Consistent with these observations, nuclear factor-kappaB activation in colonic mucosa was suppressed in the curcumin-treated mice. 6 These findings suggest that curcumin or diferuloylmethane, a major component of the food flavour turmeric, exerts beneficial effects in experimental colitis and may, therefore, be useful in the treatment of IBD.

Catalposide, A compound isolated from Catalpa ovata, attenuates induction of intestinal epithelial proinflammatory gene expression and reduces the severity of trinitrobenzene sulfonic acid-induced colitis in mice

Catalposide, A compound isolated from Catalpa ovata, attenuates induction of intestinal epithelial proinflammatory gene expression and reduces the severity of trinitrobenzene sulfonic acid-induced colitis in mice

NCX-1015, a nitric-oxide derivative of prednisolone, enhances regulatory T cells in the lamina propria and protects against 2,4,6-trinitrobenzene sulfonic acid-induced colitis in mice.

NCX-1015 is a nitric oxide (NO)-releasing derivative of prednisolone. In this study we show NCX-1015 protects mice against the S. A. development and induces healing of T helper cell type 1-mediated experimental colitis induced by intrarectal administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS). The beneficial effect of NCX-1015 was reflected in increased survival rates, improvement of macroscopic and histologic scores, a decrease in the mucosal content of T helper cell type 1 cytokines (protein and mRNA), and diminished myeloperoxidase activity in the colon. In contrast to its NO derivative, only very high doses of prednisolone were effective in reproducing these beneficial effects. NCX-1015 was 10- to 20-fold more potent than the parent compound in inhibiting IFN-gamma secretion by lamina propria mononuclear cells. Protection against developing colitis correlated with inhibition of nuclear translocation of p65Rel A in these cells. In vivo treatment with NCX-1015 potently stimulated IL-10 production, suggesting that the NO steroid induces a regulatory subset of T cells that negatively modulates intestinal inflammation.

Evaluation of the Role of Neutrophils in the Pathogenesis of Acetic Acid-Induced Colitis in Mice

Background: Neutrophils are thought to play a role in the pathogenesis of inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease, since prominent neutrophil infiltration has been observed in the inflamed colonic mucosa of patients with IBD. However, the role of neutrophils in the pathogenesis of IBD and experimental colitis remains equivocal. The aim of the present study is to clarify the possible role of neutrophils in the progression of acetic acid-induced colitis in mice. Methods: Using neutropenic mice treated with cyclophosphamide or with an LTB4 receptor antagonist, ONO-4057, the relationship between the severity of macroscopic colonic damage, the extent of myeloperoxidase (MPO) activities in the colonic tissues, and the number of neutrophils in the blood were examined after induction of colitis in mice. Results: Changes of MPO activity in the colonic tissues paralleled well with the severity of the mucosal damage. In spite of a significant reduction in the number of neutrophils in the blood in cyclophosphamide-treated mice, neither the severity of mucosal damage in the colon nor the increase in MPO activities in the colonic tissues was affected 24 h after induction of colitis. Treatment with ONO-4057 significantly suppressed both the severity of mucosal damage in the colon and MPO activities in the colonic tissues in acetic acid-induced colitis in mice. Conclusions: The present results, obtained using treatment with cyclophosphamide and ONO-4057, show that the severity or the progression of acetic acid-induced colitis in mice was not influenced by a reduction of circulating neutrophils to about 25% of base line.

Evaluation of the role of mast cells in the progression of acetic acid-induced colitis in mice.

Mast cells are widely distributed in the gastrointestinal mucosa. However, their role in the pathogenesis of inflammatory bowel disease remains unsettled. The aim of the present study is to clarify the relative importance of mast cells in the progression of acetic acid-induced colitis in mice. Mast cell-deficient W/Wv and their normal littermate +/+ mice were given intrarectal administration of 5% acetic acid. The severity of colonic damage, the number of mast cells, and myeloperoxidase (MPO) activities in the colonic tissues were examined. The severity of colonic damage was comparable between W/Wv and +/+ mice. In both groups of animals kinetic changes of the severity of the mucosal damage agreed well with that of MPO activities in the colonic mucosa. Pretreatment with a mast cell stabilizer, ketotifen, did not affect the severity of colitis in +/+ mice. These results discount, but do not disprove, the role of mast cells in the progression of acetic acid-induced colitis in mice.

Inhibition of butyric acid-induced colitis in mice by 16,16-dimethyl prostaglandin E2

Inhibition of butyric acid-induced colitis in mice by 16,16-dimethyl prostaglandin E2

Inhibition of butyric acid-induced colitis in mice by 16,16-dimethyl prostaglandin E2

A standard colitic lesion was induced in male BKA mice by intrarectal administration of butyric acid (7.5%, 0.1 ml, 10 sec contact). Animals were killed after 5 h and the 'colitic score', increase in colonic tissue water ('oedema') and colonic tissue content of myeloperoxidase (MPO, a marker for neutrophils) were determined. Drug was administered intrarectally in 0.2 ml saline 20 min before colitis induction. In colitic animals given vehicle alone, all these parameters increased (P less than 0.05) compared to the non-colitic controls. In colitic animals given 16,16-dimethyl PGE2 (0.2-20000 micrograms/kg), colitic score was reduced (P less than 0.05) at all dose levels when compared with vehicle-treated colitic animals. The oedema and MPO showed a dose-related reduction (r = -0.895 and -0.904 respectively). In mouse colon 16,16-dimethyl PGE2 showed a protective action against butyric acid-induced colitic damage.

Superoxide dismutase(SOD) protect against acetic acid-induced colitis in mice

Superoxide dismutase(SOD) protect against acetic acid-induced colitis in mice