Trinitrobenzenesulfonic Acid Model Research Articles

Prebiotic, antioxidant and anti-inflammatory properties of edible Amazon fruits

Abstract Dietary products with prebiotic and antioxidant properties may be used to protect against chronic diseases, including inflammatory bowel diseases. Assai berry, burity palm and cupuassu from the Amazon are functional foods because of their high level of dietary fiber and polyphenols, which have an important role in the prevention of inflammatory processes. Their activity as a dietary supplement was measured using fruit pulp flours in a trinitrobenzenesulphonic acid model of intestinal inflammation. The intestinal anti-inflammatory effects were evaluated using clinical parameters and biochemical analysis of pro-inflammatory cytokines (IL-6, IL-1β and TNF-α), whereas antioxidant activity was studied using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, mieloperoxidase (MPO) and alkaline phosphatase (ALP) activities, glutathione (GSH) level and phenolic content. The effects of dietary supplementation on the mucin release and short-chain fatty acid (SCFA) production were studied. Assai berry and burity palm reduced MPO and ALP activities, counteracted GSH and propionate reductions induced by the inflammatory process as well as decreased IL-6, IL-1β and TNF-α levels and increased mucin production. Cupuassu reduced MPO and ALP activities, IL-6 and IL-1β levels and increased colonic mucin, without effects on the SCFA production and TNF-α colonic level. In vitro studies showed the antioxidant properties, which were associated with the presence of polyphenol compounds and scavenging activity using the DPPH assay. The results indicated the possible benefits of using assai berry and burity palm fruits as dietary antioxidant, prebiotic, immune modulators and anti-inflammatory complementary products to treat intestinal inflammation.

Dietary intervention with green dwarf banana flour (Musa sp. AAA) modulates oxidative stress and colonic SCFAs production in the TNBS model of intestinal inflammation

Abstract Dietary products with prebiotic properties have been used to promote protective effects during inflammatory process. Prebiotics are source of short chain fatty acids (SCFAs) that have been associated with anti-inflammatory effects. Banana (Musa sp. AAA) is rich in resistant starch, which is used by colonic microbiota to SCFAs production. For this, we used the trinitrobenzenesulphonic acid model of intestinal inflammation to evaluate whether intestinal anti-inflammatory effect is related to prebiotic effects. Dietary intervention with green dwarf banana flour (5% or 10%) increased acetate, propionate and butyrate concentration. The protective effects was also evidenced by reduction in extension of lesion, inhibition of myeloperoxidase activity, prevention in glutathione depletion, increased mucin production and mucosal healing. This way, dietary green dwarf banana modulates oxidative stress and colonic production of SCFAs increasing intestinal tissue protection and may be used as a complementary product to prevent or avoid relapse of symptoms in inflammatory bowel diseases.

Effect of aqueous and particulate silk fibroin in a rat model of experimental colitis

Silk fibroin (SF) has anti-inflammatory properties and promotes wound healing. Moreover, SF particles act as carriers of active drugs against intestinal inflammation due to their capacity to deliver the compound to the damaged colonic tissue. The present work assesses the effect of SF in the trinitrobenzenesulfonic acid model of rat colitis that resembles human intestinal inflammation. SF (8mg/kg) was administered in aqueous solution orally and in two particulate formats by intrarectal route, following two technologies: spray drying to make microparticles and desolvation in organic solvent to produce nanoparticles. SF treatments ameliorated the colonic damage, reduced neutrophil infiltration and improved the compromised oxidative status of the colon. They also reduced the gene expression of pro-inflammatory cytokines like IL-1β and the anti-inflammatory cytokine IL-10. Moreover, they improved the intestinal wall integrity by increasing the gene expression of some of its markers (villin, trefoil factor-3 and mucins), thus accelerating the healing. The immunomodulatory properties of SF particles were also tested in vitro in macrophages: they activated the immune response in basal conditions without increasing it after a pro-inflammatory insult. In conclusion, SF particles could be useful as carriers to deliver active drugs to the damaged intestinal colon with additional anti-inflammatory and healing properties.

Intestinal anti-inflammatory activity of the polyphenolic-enriched extract Amanda® in the trinitrobenzenesulphonic acid model of rat colitis

Alternative herbal therapy is increasingly used for inflammatory bowel disease (IBD), but it is essential to prove its safety and efficacy. We have assayed the anti-inflammatory effects of Amanda®, a standardized water extract of Spanish Marcona almond skin very rich in polyphenols, in the trinitrobenzenesulphonic acid (TNBS) model of rat colitis. Amanda® reduced the inflamed/ulcerated colonic area and preserved the mucosal architecture. The extract decreased the inflammatory infiltrate and the myeloperoxidase activity, as well as improved the oxidative state by increasing the glutathione content. Amanda® also modulated the expression of pro-inflammatory cytokines and inducible nitric oxide synthase. Besides, Amanda® improved the epithelial barrier function by restoring the levels of villin and mucin MUC3. Thus, the data from this work prove that Amanda® extract possesses therapeutic activity in TNBS-induced colitis in rats, targeting different pathological factors of IBD like oxidative stress, neutrophil mucosal infiltration and loss of intestinal epithelial barrier function.

Silk fibroin nanoparticles constitute a vector for controlled release of resveratrol in an experimental model of inflammatory bowel disease in rats.

PurposeWe aimed to evaluate the intestinal anti-inflammatory properties of silk fibroin nanoparticles, around 100 nm in size, when loaded with the stilbene compound resveratrol, in an experimental model of rat colitis.MethodsNanoparticles were loaded with resveratrol by adsorption. The biological effects of the resveratrol-loaded nanoparticles were tested both in vitro, in a cell culture of RAW 264.7 cells (mouse macrophages), and in vivo, in the trinitrobenzenesulfonic acid model of rat colitis, when administered intracolonically.ResultsThe resveratrol liberation in 1× phosphate-buffered saline (PBS; pH 7.4) was characterized by fast liberation, reaching the solubility limit in 3 hours, which was maintained over a period of 80 hours. The in vitro assays revealed immunomodulatory properties exerted by these resveratrol-loaded nanoparticles since they promoted macrophage activity in basal conditions and inhibited this activity when stimulated with lipopolysaccharide. The in vivo experiments showed that after evaluation of the macroscopic symptoms, inflammatory markers, and intestinal barrier function, the fibroin nanoparticles loaded with resveratrol had a better effect than the single treatments, being similar to that produced by the glucocorticoid dexamethasone.ConclusionSilk fibroin nanoparticles constitute an attractive strategy for the controlled release of resveratrol, showing immunomodulatory properties and intestinal anti-inflammatory effects.

Intestinal anti-inflammatory effects of oligosaccharides derived from lactulose in the trinitrobenzenesulfonic acid model of rat colitis.

Intestinal microbiota modulation is becoming an interesting approach to manage inflammatory bowel disease and can be achieved by the administration of prebiotics. Previous studies showed the intestinal anti-inflammatory effects of the prebiotic lactulose. The aim of the present study was to test the preventative effects of oligosaccharides derived from lactulose with prebiotic properties (OsLu) in the trinitrobenzenesulfonic acid model of rat colitis and compare them with those of lactulose. Both treatments modified bacterial profile in intestinal contents, increasing the bifidobacteria and lactobacilli counts and up-regulating the production of short-chain fatty acids, although OsLu generated a larger amount. OsLu also inhibited to a greater extent different pro-inflammatory markers such as interleukins (IL) 1, 6, 12, and 23 and chemokines (MCP-1 and CINC-1). However, both prebiotics equally restored colonic epithelial integrity, evaluated both with a histological score (OsLu, 9.8 ± 2.2; and lactulose, 12.1 ± 2.1, vs colitic control, 27.3 ± 3.3) and by measuring several key proteins of the mucosal barrier (MUC-2, MUC-3, and TTF-3). OsLu effect was also associated with an inhibition of iNOS expression and a reduction of Th17 cell activity in the inflamed tissue that facilitated the intestinal mucosa barrier recovery. In conclusion, OsLu showed a better anti-inflammatory profile than lactulose in this model of experimental colitis.

Intestinal anti-inflammatory activity of hydroalcoholic extracts of Phlomis purpurea L. and Phlomis lychnitis L. in the trinitrobenzenesulphonic acid model of rat colitis.

Different species from genus Phlomis, frequently native from the the eastern Mediterranean zone, have been used in traditional medicine as an anti-inflammatory remedy. Among other constituents, they contain polyphenols that show antioxidant properties, which are interesting for the treatment of inflammatory pathologies associated with oxidative stress in humans, such as inflammatory bowel disease (IBD). The aim of this study was to evaluate the intestinal anti-inflammatoy effect of hydroalcoholic extracts of Phlomis lychnitis and P. purpurea in the trinitrobenzenesulphonic acid (TNBS) model of rat colitis, a well characterized experimental model with some resemblance to human IBD. Hydroalcoholic extracts of both plants were characterized by determining their polyphenolic content and then assayed in the TNBS model of rat colitis. For this purpose, female Wistar rats were assigned to seven groups (n=10): healthy control, untreated TNBS-colitis and five TNBS- colitis groups treated with Phlomis lychnitis (10 and 20mg/kg), P. purpurea (10 and 25mg/kg) and sulphasalazine (200mg/kg), as a positive control. Treatments started the same day of TNBS colitis induction, and rats were sacrificed one week later. Colonic inflammation was evaluated both histologically and biochemically. The histological (macroscopic and microscopic) analysis of colonic samples revealed that both extracts showed an anti-inflammatory effect, which was confirmed biochemically by a decreased colonic MPO activity, a maker of neutrophil infiltration, an increased colonic glutathione content, which counteracts the oxidative status associated with the inflammatory process, and a down-regulated iNOS expression. However, only the extract of P. purpurea reduced the expression of the proinflammatory cytokines IL-1β and IL-17, the chemokines CINC-1 and MCP-1, as well as the adhesion molecule ICAM-1, ameliorating the altered immune response associated with the colonic inflammation. Furthermore, both P. lychnitis and P. purpurea extracts were able to significantly increase the expression of markers of epithelial integrity such as MUC-2, MUC-3 and villin, thus revealing an improvement in the altered colonic permeability that characterizes colonic inflammation. Both extracts showed intestinal anti-inflammatory activity in the TNBS model of rat colitis, thus confirming their traditional use in digestive inflammatory complaints. In addition to their antioxidant properties, other mechanisms can contribute to this beneficial effect, like an improvement in the intestine epithelial barrier and a downregulation of the immune response.

Active hexose-correlated compound and Bifidobacterium longum BB536 exert symbiotic effects in experimental colitis

Active hexose-correlated compound (AHCC) is a commercial extract obtained from Basidiomycetes under controlled conditions, yielding a 74 % content in oligosaccharides, especially α-glucans. AHCC has a number of therapeutic effects, including intestinal anti-inflammatory activity. Bifidobacterium longum BB536 is a probiotic with potential health-promoting effect at the gut level. The purpose of the present study was to evaluate the possibility of synergism between AHCC, which is believed to act as a prebiotic, and B. longum BB536. We used the trinitrobenzene sulfonic acid model (TNBS) of colitis in rats. AHCC (100 or 500 mg kg(-1)) and B. longum BB536 (5 × 10(6) CFU rat(-1) day(-1)) were administered together or separately for 7 days prior to colitis induction and then for another 7 days and compared with control (noncolitic) and TNBS rats. The results show that both treatments had intestinal anti-inflammatory activity separately, which was enhanced when used in combination, as shown by changes in body weight gain, colonic weight to length ratio, myeloperoxydase activity and iNOS expression. Interestingly, the association of AHCC 100 mg kg(-1) + B. longum BB536 showed the highest anti-inflammatory activity. Our data provide a preclinical experimental basis for the synergistic effect of AHCC and B. longum BB536 on inflammatory bowel disease.

Dietary intervention with narrow-leaved cattail rhizome flour (Typha angustifolia L.) prevents intestinal inflammation in the trinitrobenzenesulphonic acid model of rat colitis

BackgroundInflammatory bowel disease (IBD) is a chronic inflammation of the intestinal epithelium that is driven by the intestinal immune system, oxidative stress and the loss of tolerance to the luminal microbiota. The use of dietary products containing ingredients such as fibres and carbohydrates and/or antioxidant compounds have been used as a therapeutic strategy for intestinal diseases because these products are considered effective in the modulation of the immune system and colonic microbiota. We investigated the beneficial effects of cattail rhizome flour (Typha angustifolia L.) in the trinitrobenzenesulphonic acid (TNBS) model of rat colitis. In addition, we investigated the effects of cattail rhizome flour on the intestinal anti-inflammatory activity of prednisolone, which is a reference drug that is used for treatment of human IBD.MethodsThe present study included the preparation of flour from rhizomes of cattail (Typha angustifolia L.); an evaluation of the qualitative phytochemical profile of cattail rhizomes; an evaluation of the efficacy of cattail rhizome flour in TNBS-induced rat colitis; an evaluation of the synergistic effects of cattail rhizome flour on the intestinal anti-inflammatory activity of prednisolone; and macroscopic, clinical, biochemical, histopathological and microbiological studies to assess the healing effects of cattail rhizome flour and its synergistic effects in TNBS-induced rat colitis. The data were analysed by ANOVA, Kruskal-Wallis and χ2 tests.ResultsWe tested several concentrations of cattail rhizome flour and found that dietary supplementation with 10% cattail rhizome flour showed the best effects at reducing the extension of the lesion, the colon weight ratio, adherences to adjacent organs and diarrhoea. These effects were related to inhibition of myeloperoxidase (MPO) and alkaline phosphatase (AP) activities and an attenuation of glutathione (GSH) depletion. The 10% cattail rhizome flour was as effective as prednisolone, and no synergistic effects were observed. Saponins, flavonoids and coumarins were detected in the rhizome flour. No changes were observed in the total number of lactic bacteria after dietary supplementation with cattail rhizome flour.ConclusionsDietary supplementation with 10% cattail rhizome flour and its combination with prednisolone prevent TNBS-induced colonic damage in rats, but no synergistic effects were observed. The prevention of TNBS-induced colon damage was associated with an improvement in intestinal oxidative stress, which likely resulted from the antioxidant properties of the active compounds detected in the cattail rhizome. This protective effect was not related to an improvement in lactic bacteria counts.

Dietary intervention with green dwarf banana flour (Musa sp AAA) prevents intestinal inflammation in a trinitrobenzenesulfonic acid model of rat colitis

Dietary products are among the therapeutic approaches used to modify intestinal microflora and to promote protective effects during the intestinal inflammatory process. Because the banana plant is rich in resistant starch, which is used by colonic microbiota for the anaerobic production of the short-chain fatty acids that serve as a major fuel source for colonocytes: first, green dwarf banana flour produces protective effects on the intestinal inflammation acting as a prebiotic and, second, combination of this dietary supplementation with prednisolone presents synergistic effects. For this, we used the trinitrobenzenesulphonic acid (TNBS) model of rat colitis. Our results revealed that the protective effect produced by a combination of 10% green dwarf banana flour with prednisolone was more pronounced than those promoted by a single administration of prednisolone or a diet containing 10% or 20% banana flour. This beneficial effect was associated with an improvement in the colonic oxidative status because the banana flour diet prevented the glutathione depletion and inhibited myeloperoxidase activity and lipid peroxidation. In addition, the intestinal anti-inflammatory activity was associated with an inhibition of alkaline phosphatase activity, a reduction in macroscopic and microscopic scores, and an extension of the lesions. In conclusion, the dietary use of the green dwarf banana flour constitutes an important dietary supplement and complementary medicine product to prevention and treatment of human inflammatory bowel disease.

Differential patterns of histone acetylation in inflammatory bowel diseases

Post-translational modifications of histones, particularly acetylation, are associated with the regulation of inflammatory gene expression. We used two animal models of inflammation of the bowel and biopsy samples from patients with Crohn's disease (CD) to study the expression of acetylated histones (H) 3 and 4 in inflamed mucosa. Acetylation of histone H4 was significantly elevated in the inflamed mucosa in the trinitrobenzene sulfonic acid model of colitis particularly on lysine residues (K) 8 and 12 in contrast to non-inflamed tissue. In addition, acetylated H4 was localised to inflamed tissue and to Peyer's patches (PP) in dextran sulfate sodium (DSS)-treated rat models. Within the PP, H3 acetylation was detected in the mantle zone whereas H4 acetylation was seen in both the periphery and the germinal centre. Finally, acetylation of H4 was significantly upregulated in inflamed biopsies and PP from patients with CD. Enhanced acetylation of H4K5 and K16 was seen in the PP. These results demonstrate that histone acetylation is associated with inflammation and may provide a novel therapeutic target for mucosal inflammation.

Intestinal anti-inflammatory activity of esculetin and 4-methylesculetin in the trinitrobenzenesulphonic acid model of rat colitis

Coumarins comprise a broad class of phenolic compounds that influences the formation and scavenging of reactive oxygen species and the processes involving free radical-mediated injury. In light of the antioxidant and anti-inflammatory properties of esculetin and 4-methylesculetin, the aim of this study was to investigate the effects of these compounds in an experimental model of rat colitis induced by trinitrobenzenesulphonic acid (TNBS). For this purpose, macroscopic (diarrhoea, extension of lesion, colonic weight/length ratio and damage score) and biochemical parameters (myeloperoxidase, alkaline phosphatase and glutathione) were evaluated. Our results reveal that these compounds, particularly 4-methylesculetin, may be effective for the treatment of intestinal inflammatory bowel disease. In the acute colitis model, esculetin promoted a reduction in the extension of the lesion accompanied by a reduction in the incidence of diarrhoea and restoration of the glutathione content. Similar effects were produced by the administration of 4-methylesculetin, which also inhibited the myeloperoxidase and alkaline phosphatase activities in the acute intestinal inflammatory process and in the model of colitis relapse. The effect of the esculetin and 4-methylesculetin on the inflammatory process may be related to their antioxidant and anti-inflammatory properties, as observed in this study. The evidence for better effects of 4-methylesculetin in comparison to those demonstrated by esculetin in both experimental settings could be attributed to the presence of the methyl group at C-4 of 4-methylesculetin.

Induction of IDO-1 by Immunostimulatory DNA Limits Severity of Experimental Colitis

The chronic inflammatory bowel diseases are characterized by aberrant innate and adaptive immune responses to commensal luminal bacteria. In both human inflammatory bowel disease and in experimental models of colitis, there is an increased expression of the enzyme IDO. IDO expression has the capacity to exert antimicrobial effects and dampen adaptive immune responses. In the murine trinitrobenzene sulfonic acid model of colitis, inhibition of this enzyme leads to worsened disease severity, suggesting that IDO acts as a natural break in limiting colitis. In this investigation, we show that induction of IDO-1 by a TLR-9 agonist, immunostimulatory (ISS) DNA, critically contributes to its colitis limiting capacities. ISS DNA induces intestinal expression of IDO-1 but not the recently described paralog enzyme IDO-2. This induction occurred in both epithelial cells and in subsets of CD11c(+) and CD11b(+) cells of the lamina propria, which also increase after ISS-oligodeoxynucleotide. Signaling required for intestinal IDO-1 induction involves IFN-dependent pathways, as IDO-1 was not induced in STAT-1 knockout mice. Using both the trinitrobenzene sulfonic acid and dextran sodium sulfate models of colitis, we show the importance of IDO-1s induction in limiting colitis severity. The clinical parameters and histological correlates of colitis in these models were improved by administration of the TLR-9 agonist; however, when the function of IDO is inhibited, the colitis limiting effects of ISS-oligodeoxynucleotide were abrogated. These findings support the possibility that targeted induction of IDO-1 is an approach deserving further investigation as a therapeutic strategy for diseases of intestinal inflammation.

Effect of grape seeds on the IL-10 and IL-12 in the trinitrobenzenesulfonic acid model of rat colitis

Effect of grape seeds on the IL-10 and IL-12 in the trinitrobenzenesulfonic acid model of rat colitis

Genomic analysis of sulfasalazine effect in experimental colitis is consistent primarily with the modulation of NF-κB but not PPAR-γ signaling

Sulfasalazine (SAZ) is a widely used drug in inflammatory bowel disease patients but its mechanism of action is incompletely understood. The objective of our study was to further characterize SAZ mechanism by studying its effect on the colonic transcriptome in a suitable preclinical model of inflammatory bowel disease. The trinitrobenzenesulfonic acid model of colitis in rats was used. The effect of SAZ on mRNA expression was assessed with Affymetrix Rat Expression 230 2.0 arrays used in triplicate (sextuplicate for controls), validated in separate samples with quantitative reverse-time PCR analysis. Some nongenomic experiments were also carried out. SAZ (500 mg/kg) had a marked anti-inflammatory effect as expected, which was correlated with a dramatic impact on colonic gene expression. In addition to immune/inflammatory genes, SAZ responsive genes were involved in distinct metabolic and signaling pathways. The effect of sulfasalazine was generally of normalization of colitis-modulated genes to control levels, with very few exceptions. Postgenomic validation showed an excellent correlation with microarray data and seemed to be slightly more sensitive. SAZ generally modulated the expression of nuclear factor-kappaB-driven genes. SAZ was also shown to inhibit IkappaB-alpha phosphorylation in rat primary splenocytes and in HT29 and IEC18 cells. In contrast, SAZ had only a modest effect on peroxisome proliferator-activated receptor (PPAR)-gamma-regulated genes and it was confirmed to induce PPAR-gamma in enterocytes but not splenocytes. Mechanistically, our data are consistent primarily with nuclear factor-kappaB inhibition, and there is little evidence of a prominent role of activation of PPAR-gamma receptors or antioxidative actions.

Therapeutic Potential of Two Probiotics in Inflammatory Bowel Disease as observed in the Trinitrobenzene Sulfonic Acid Model of Colitis

The pathogenesis of inflammatory bowel disease is thought to be a multifactorial process. One of the leading hypotheses is that an imbalance in normal gut flora induces an excessive immune response and contributes to inflammation in the gastrointestinal tract. Administration of probiotic bacteria reduces symptoms in patients suffering from inflammatory bowel diseases, probably via both manipulation of the microflora and stimulation of the intestinal immune system. In the current study the therapeutic potential of two different probiotics-Lactobacillus GG and a mixture of Streptococcus thermophilus, Lactobacillus acidophilus, and Bifidobacterium longum (YO-MIX Y 109 FRO 1000)--in a rat model of colitis were evaluated. Male Wistar rats were administered probiotics for three days simultaneously with colitis induction. Colonic damage was evaluated histologically and biochemically and colonic tissues, as well as fecal samples, were used for bacterial studies using 16S rRNA gene primers. Probiotics administration reduced the relative amounts of the pathogenic bacteria Aeromonas and Escherichia coli in the colonic tissue. However, whereas both probiotics affected colon morphology, only Lactobacillus GG administration reduced myeloperoxidase activity. We report the therapeutic rather than preventive potential of two different probiotics in an animal model of colitis.

Intestinal Anti-inflammatory Activity of Coumarin and 4-Hydroxycoumarin in the Trinitrobenzenesulphonic Acid Model of Rat Colitis

Coumarins represent an important class of phenolic compounds with multiple biological activities, including inhibition of lipidic peroxidation and neutrophil-dependent anion superoxide generation, anti-inflammatory and immunosuppressor actions. All of these proprieties are essential for that a drug may be used in the treatment of inflammatory bowel disease. The present study examined intestinal anti-inflammatory activity of coumarin and its derivative, the 4-hydroxycoumarin on experimental ulcerative colitis in rats. This was performed in two different experimental settings, i.e. when the colonic mucosa is intact or when the mucosa is in process of recovery after an initial insult. The results obtained revealed that the coumarin and 4-hydroxycoumarin, at doses of 5 and 25 mg/kg, significantly attenuated the colonic damage induced by trinitrobenzenesulphonic acid (TNBS) in both situations, as evidenced macroscopically, microscopically and biochemically. This effect was related to an improvement in the colonic oxidative status, since coumarin and 4-hydroxycoumarin prevented the glutathione depletion that occurred as a consequence of the colonic inflammation.

The bisphosphonate alendronate improves the damage associated with trinitrobenzenesulfonic acid‐induced colitis in rats

The nitrogen-containing bisphosphonates are drugs used successfully in the treatment of osteoporosis. They act inhibiting farnesyl diphosphate synthase. This mechanism may also produce anti-inflammatory effects. The therapeutic activity of alendronate was tested in vivo using a model of inflammatory bowel disease. The trinitrobenzenesulfonic acid model of colitis in the rat was used. Rats were treated orally with alendronate and its efficacy compared with that of oral sulphasalazine or vehicle, starting 2 h after colitis induction. The status of the animals was assessed 5 days later. Alendronate treatment (25 or 75 mg kg(-1) day(-1)) resulted in a decrease in the colonic damage score and loss of body weight (at 25 mg kg(-1) day(-1) only). This was associated to a dramatic reduction in the mRNA levels of interleukin 1 beta (IL-1 beta), monocyte chemoattractant protein 1 (MCP-1) and interleukin 1 receptor antagonist (IL-1 ra). The magnitude of the beneficial effect was comparable to that of sulphasalazine (at a 6-20 fold higher dose). Thus sulphasalazine post-treatment reduced the mRNA levels of IL-1 beta/IL-1 ra and MCP-1 to the same extent as alendronate and additionally lowered colonic alkaline phosphatase activity, but failed to affect body weight loss or colonic damage score. Alendronate failed to exert beneficial effects when administered intraperitoneally. Oral but not intraperitoneal alendronate significantly protected the colon in experimental rat colitis. Inflammatory bowel disease patients might benefit from exposure to oral alendronate.

A comparative study of the preventative effects exerted by two probiotics,Lactobacillus reuteriandLactobacillus fermentum, in the trinitrobenzenesulfonic acid model of rat colitis

The intestinal anti-inflammatory effects of two probiotics isolated from breast milk, Lactobacillus reuteri and L. fermentum, were evaluated and compared in the trinitrobenzenesulfonic acid (TNBS) model of rat colitis. Colitis was induced in rats by intracolonic administration of 10 mg TNBS dissolved in 50% ethanol (0.25 ml). Either L. reuteri or L. fermentum was daily administered orally (5 x 10(8) colony-forming units suspended in 0.5 ml skimmed milk) to each group of rats (n 10) for 3 weeks, starting 2 weeks before colitis induction. Colonic damage was evaluated histologically and biochemically, and the colonic luminal contents were used for bacterial studies and for SCFA production. Both probiotics showed intestinal anti-inflammatory effects in this model of experimental colitis, as evidenced histologically and by a significant reduction of colonic myeloperoxidase activity (P<0.05). L. fermentum significantly counteracted the colonic glutathione depletion induced by the inflammatory process. In addition, both probiotics lowered colonic TNFalpha levels (P<0.01) and inducible NO synthase expression when compared with non-treated rats; however, the decrease in colonic cyclo-oxygenase-2 expression was only achieved with L.fermentum administration. Finally, the two probiotics induced the growth of Lactobacilli species in comparison with control colitic rats, but the production of SCFA in colonic contents was only increased when L. fermentum was given. In conclusion, L. fermentum can exert beneficial immunomodulatory properties in inflammatory bowel disease, being more effective than L. reuteri, a probiotic with reputed efficacy in promoting beneficial effects on human health.

Inulin and oligofructose: impact on intestinal diseases and disorders

A large and diverse variety of bacteria have evolved and adapted to live in the human intestinal habitat in a symbiotic arrangement that influences both physiology and pathology in the host. Symbiosis between host and flora can be optimised by prebiotics. Inulin-type fructans have been shown to improve the metabolic functions of the commensal flora. Clinical and experimental data suggest that they also improve the gut mucosal barrier. Furthermore, modulation of the trophic functions of the flora by these prebiotics could help in the prevention of inflammatory bowel diseases. The anti-inflammatory effects of inulin or oligofructose have been assessed in the rat model of distal colitis induced by dextran sodium sulphate, which histologically resembles human ulcerative colitis, and in the trinitrobenzene sulphonic acid model that resembles human Crohn's disease. Both inulin and oligofructose stimulate colonic production of SCFA and favour the growth of indigenous lactobacilli and/or bifidobacteria. These effects are associated with reduced mucosal inflammation and decreased mucosal lesion scores. Inulin has also been tested in a placebo-controlled clinical trial in patients with relapsing pouchitis. Treatment reduced endoscopic and histological parameters of inflammation of the pouch mucosa. Inulin and oligofructose may offer an opportunity to prevent chronic inflammatory intestinal disorders, and this potential should be tested in further clinical studies.