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New therapeutic strategies against inflammatory bowel disease (IBD) consider the usage of probiotics, prebiotics and synbiotics as beneficial for the intestinal microbial balance. Limitations of such an approach are addressed into difference in survival, persistence, colonization and variable effects among different probiotic strains, lack in understanding of probiotic mechanisms of action, as well the complex etiology of IBD. The anti-inflammatory activity of Lactobacillus casei 01 ( L. casei 01) was assessed in trinitrobenzenesulphonic (TNBS) acid model of rat colitis when the probiotic was used alone and/or in combination with oligofructose-enriched inulin (Synergy 1), and as synbiotic ( L. casei 01 + Synergy 1) loaded chitosan-Ca-alginate microparticles; all suspended in ayran. The results from the probiotic/synbiotic treatments (8.5–8.9 log CFU g −1 L. casei 01 and 1.5% Synergy 1) have shown reduction in the colonic damage and increased lactobacilli counts in feces. Lactobacilli translocation to sterile extra-intestinal organs demonstrated acceptable safety of the probiotic strain used. The best effect at reducing inflammation and lesions associated with a significant decline in myeloperoxidase (MPO) activity was observed in rats that received synbiotic microparticles. This finding suggests colon targeted delivery of the probiotics/synbiotics, as an advantageous approach in prevention and treatment of IBD. [ABSTRACT FROM AUTHOR]

PURPOSE: To evaluate the effect of soluble fiber or fructooligosaccharide (FOS) supplementation upon trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. METHODS: 64 Wistar rats were given water, soluble fiber or FOS intragastrically during 14 days prior to colitis induction with TNBS (n=48) or rectal enema with water (n=16; control group). On the 7th or 14th day following colitis induction the rats were weighed and euthanized in order to determine the colon weight/length ratio and macroscopic and microscopic scores. RESULTS: On the 7th day following colitis induction the body weight had decreased significantly, the colon weight/length ratio had increased and macroscopic and microscopic colon lesions were observed. On the 14th day following colitis induction no difference in body weight was observed, in spite of the persistence of macroscopic and microscopic lesions and increased colon weight/length ratio. Supplementation with soluble fiber or FOS did not revert colon lesions or any of the study parameters. Supplementation with FOS, but not with fiber, was associated with increased colon weight/length ratio on the 14th day. CONCLUSION: Supplementation with soluble fiber or FOS produced no significant impact on TNBS-induced colitis in rats.OBJETIVO: Avaliar a suplementação de fibra solúvel ou frutooligossacarídeos (FOS) na colite induzida por TNBS em ratos. MÉTODOS: Sessenta e quatro ratos Wistar receberam por gavagem água, fibra solúvel ou FOS. Após 14 dias, foram submetidos à indução de colite com TNBS. O grupo controle recebeu água por gavagem e por enema retal. Decorridos 7 ou 14 dias, após a avaliação do peso, os ratos foram sacrificados e o peso do colo, escores macroscópicos e microscópicos da lesão cólica foram aferidos. RESULTADOS: No 7º dia após indução da colite, houve uma significativa diminuição do peso dos ratos, um aumento do peso do cólon e lesão cólica macroscópica/microscópica. A suplementação com fibra ou FOS não reverteu nenhum destes parâmetros. No 14° dia após a indução da colite não foram observadas diferenças no peso dos ratos, entretanto houve uma persistência da lesão cólica macroscópica/microscópica e do aumento do peso do cólon. A suplementação com fibra ou FOS não reverteu à lesão cólica. A suplementação de FOS, mas não de fibra, aumentou o peso do colo comparado com o grupo colite no 14° dia. CONCLUSÃO: A suplementação com fibra solúvel ou com FOS não alterou a colite por TNBS em ratos.

Antisecretory factor (AF) is expressed in all tissues of mammals, inhibits intestinal hypersecretion and has anti-inflammatory properties as well. Endogenous AF synthesis may be stimulated by feeding hydrothermally processed cereals. Alternatively, freeze-dried egg yolk can be used as a source of exogenous AF. Several reports have suggested that AF from freeze-dried egg yolk may be useful in inflammatory bowel disease. We assessed the effect of freeze-dried, AF-rich egg yolk intake on 2,4,6-trinitrobenzenesulphonic acid (TNBS) colitis. Balb/c mice were randomised to receive (1) AF in sterile drinking-water (4 g/l, n 38) and (2) sterile drinking-water alone (vehicle, n 38) from TNBS or saline administration onwards. Different subsets of mice were killed at weeks 1–3 after TNBS or saline administration. Macroscopic and microscopic damage was assessed in colonic specimens. Eicosanoid and cytokine production was evaluated in supernatants of 24 h-incubated colonic explants. Myeloperoxidase activity was measured in frozen colonic samples, while apoptosis was assessed in paraffined samples by the in situ oligoligation method. AF-treated mice showed a milder colonic damage compared with the vehicle group, which became statistically significant at week 3. This was accompanied by decreased IL-2, IL-1 and leukotriene B4 production at weeks 2 and 3, as well as increased interferon-γ at week 1, in AF-treated mice compared with vehicle-treated mice. AF-treated mice had significantly increased counts of apoptotic cells in the lamina propria at weeks 1 and 2 post-TNBS. In conclusion, the administration of AF-rich egg yolk has a therapeutic effect in the late phases of TNBS colitis in Balb/c mice. [ABSTRACT FROM PUBLISHER]

Abstract: Aims: To investigate the effect of sildenafil citrate (SIL) on the extent of tissue integrity, oxidant–antioxidant status and apoptosis in rats with colitis. Main methods: Colitis was induced by trinitrobenzenesulphonic acid (TNBS) in 40% ethanol (30mg/ml; 0.8ml) given intrarectally to Sprague–Dawley rats. Sildenafil (25mg/kg/day) was administered after the induction of colitis and the treatment was continued for 7days. Other groups received subcutaneously either N(G)-nitro- L-arginine methyl ester (l-NAME; 25mg/kg) or N(G)-nitro-d-arginine methyl ester (d-NAME; 25mg/kg) before SIL. After decapitation, the distal colon was scored and stored for the measurement of malondialdehyde (MDA) level, glutathione (GSH) content, myeloperoxidase (MPO) activity and apoptosis. Oxidant generation was monitored by using chemiluminescence (CL). Blood was collected for tumor necrosis factor (TNF)-α and interleukin (IL)-10 assays. Key findings: The macroscopic lesion score of the colitis group was reduced by SIL (p<0.01) and this effect was abolished by l-NAME (p<0.01). Increase in colonic MDA along with a concomitant decrease in GSH of the colitis group was reversed by SIL (p<0.01 and p<0.001, respectively). l-NAME prevented the effect of SIL on GSH content (p<0.001). Sildenafil also reduced the elevated MPO of the colitis group (p<0.001) and this effect was reversed by L-NAME (p<0.01). Increase in lucigenin CL and serum TNF-α levels in the colitis group were also prevented by SIL (p<0.001 and p<0.01, respectively). Significance: Sildenafil is beneficial in TNBS-induced rat colitis partially by nitric oxide-dependent mechanisms via the maintenance of oxidant–antioxidant status, prevention of apoptosis, superoxide production and cytokine release. [Copyright &y& Elsevier]

Background and Purpose: Bovine glycomacropeptide (BGMP) is an inexpensive, non-toxic milk peptide with anti-inflammatory effects in rat experimental colitis but its mechanism of action is unclear. It is also unknown whether BGMP can ameliorate inflammation in proximal regions of the intestine. Our aim was therefore two-fold: first, to determine the anti-inflammatory activity of BGMP in the ileum; second, to characterise its mechanism of action.Experimental Approach: We used a model of ileitis induced by trinitrobenzenesulphonic acid in rats. Rats were treated orally with BGMP and its efficacy compared with that of oral 5-aminosalicylic acid or vehicle, starting 2 days before ileitis induction.Key Results: BGMP pretreatment (500 mg kg(-1) day(-1)) resulted in marked reduction of inflammatory injury, as assessed by lower extension of necrosis and damage score, myeloperoxidase, alkaline phosphatase, inducible nitric oxide synthase, interleukin 1beta, tumour necrosis factor and interleukin 17. These effects were generally comparable to those of 5-aminosalicylic acid (200 mg kg(-1) day(-1)). Neither compound affected the production of interferon gamma, tumour necrosis factor and interleukin 2 by mesenteric lymph node cells isolated from animals with ileitis. The expression of Foxp3 was increased in ileitis and not reduced significantly by BGMP or aminosalicylate treatment.Conclusions and Implications: These results demonstrate that BGMP has anti-inflammatory activity in the ileum with similar efficacy to 5-aminosalicylic acid. The mechanism of action may involve Th17 and regulatory T cells and perhaps macrophages but probably not Th1 lymphocytes. Patients with Crohn's ileitis may benefit from treatment with BGMP. [ABSTRACT FROM AUTHOR]

1: Diosmectite is a natural silicate effectively used in the treatment of infectious diarrhoea. Its antidiarrhoeal properties involve adsorption of toxins and bacteria and modifications of the rheological characteristics of gastrointestinal mucus. Hence, the aim of this study was to test the intestinal anti-inflammatory activity of diosmectite. 2: Diosmectite (500?mg?kg-1?day-1, p.o.) was administered as a post-treatment to rats with chronic trinitrobenzene sulphonic acid colitis. Colonic status was checked 1 and 2 weeks after colitis induction by macroscopic, histological and biochemical examination. 3: Diosmectite post-treatment resulted in amelioration of the morphological signs (intestinal weight, macroscopic damage, necrosed area, histology) and biochemical markers (myeloperoxidase activity, glutathione levels, MUC2 expression, inducible nitric oxide synthase and interleukin-1ß (IL-1ß) and leukotriene B4 synthesis), as well as in the reduction of the severity of diarrhoea. The effect of the clay was comparable to that of sulphasalazine (50?mg?kg-1?day-1). 4: Diosmectite exhibited a dose-dependent capacity to adsorb proteins in vitro as well as a dose-dependent inhibitory effect on the basolateral secretion of IL-8 by lipopolysaccharide (LPS)-stimulated HT29 cells. 5: Diosmectite had a dose-dependent inhibitory effect on IL-1ß production by LPS-stimulated THP-1 cells. 6: The effect of diosmectite on MUC2 was post-transcriptional, since mRNA levels were unaffected. However, diosmectite is able to upregulate MUC2 mRNA levels in HT29-MTX cells. 7: Diosmectite has anti-inflammatory activity administered as a post-treatment. Possible mechanisms include adsorption of luminal antigens, increase of colonic mucin levels and possibly a direct modulatory action of cytokine production by mucosal cells.British Journal of Pharmacology (2004) 141, 951-960. doi:10.1038/sj.bjp.0705710 [ABSTRACT FROM AUTHOR]

We used the trinitrobenzenesulphonic acid (TNBS) rat model of experimental colitis to study the alterations in electrogenic ion transport in the inflamed distal colon. The distal colon exhibited decreased basal transport and reduced short-circuit current responses to carbachol and isobutylmethylxanthine (IBMX). The concentration/response curve for IBMX was also shifted to the right. Ion substitution experiments indicated that electrogenic transport was attributable chiefly to Cl–secretion. The mucosal layer of the inflamed distal colon (devoid of the submucosa) exhibited normal maximal responses to carbachol and IBMX, although the concentration/response curve for the latter was again shifted to the right. Tetrodotoxin markedly increased the response of the normal distal colon to both secretagogues and nullified the inhibition of the response to carbachol, but not that to IBMX, in the inflamed colon. The response of the mucosal preparation to 8-bromoadenosine 3′,5′-cyclic monophosphate was similar in the normal and inflamed intestine, while the G protein activator NaF had a greater effect in the latter. The expression of the cystic fibrosis transmembrane conductance regulator (CFTR), as assessed by Northern blotting, was unchanged. cAMP levels in isolated colonocytes were markedly reduced by inflammation. We conclude that colonic inflammation produces disturbances of the enteric nervous system resulting in defective mucosal cAMP production and inhibition of ionic secretion. [ABSTRACT FROM AUTHOR]

The human newborn infant is susceptible to gut inflammatory disorders. In particular, growth-restricted infants or infants born prematurely may develop a severe form of intestinal inflammation known as necrotizing enterocolitis (NEC), which has a high mortality. Milk provides a multitude of proteins with anti-inflammatory properties and in this review we gather together some recent significant advances regarding the isolation and proteomic identification of these minor constituents of both human and bovine milk. We introduce the process of inflammation, with a focus on the immature gut, and describe how a multitude of milk proteins act against the inflammatory process according to both in vitro and in vivo studies. We highlight the effects of milk proteins such as caseins, and of whey proteins such as alpha-lactalbumin, beta-lactoglobulin, lactoferrin, osteopontin, immunoglobulins, trefoil factors, lactoperoxidase, superoxide dismutase, platelet-activating factor acetylhydrolase, alkaline phosphatase, and growth factors (TGF-β, IGF-I and IGF-II, EGF, HB-EGF). The effects of milk fat globule proteins, such as TLR-2, TLR-4, sCD14 and MFG-E8/lactadherin, are also discussed. Finally, we indicate how milk proteins could be useful for the prophylaxis and therapy of intestinal inflammation in infants and children., (Copyright © 2013 Elsevier Ltd. All rights reserved.)