Animal Model Of Acute Colitis Research Articles

Oyster Peptides Ameliorate Dextran Sulfate Sodium-Induced Ulcerative Colitis via Modulating the Gut Microbiota and Inhibiting the TLR4/NF-κB Pathway.

Ulcerative colitis (UC) is an inflammatory bowel disease with an increasing prevalence year over year, and the medications used to treat patients with UC clinically have severe side effects. Oyster peptides (OPs) have anti-inflammatory and antioxidant properties as functional foods that can alleviate a wide range of inflammatory conditions. However, the application of oyster peptides in ulcerative colitis is not well studied. In this work, an animal model of acute colitis was established using 3% dextran sulfate sodium (DSS), and the impact of OP therapy on colitis in mice was examined. Supplementing with OPs prevented DSS-induced colitis from worsening, reduced the expression of oxidative stress and inflammatory markers, and restored the intestinal barrier damage caused by DSS-induced colitis in mice. The 16S rDNA results showed that the OP treatment improved the gut microbiota structure of the UC mice, including increasing microbial diversity, increasing beneficial bacteria, and decreasing harmful bacteria. In the UC mice, the OP therapy decreased the relative abundance of Family_XIII_AD3011_group and Prevotella_9 and increased the relative abundance of Alistipes. In conclusion, OP treatment can inhibit the TLR4/NF-κB pathway and improve the intestinal microbiota in UC mice, which in turn alleviates DSS-induced colitis, providing a reference for the treatment of clinical UC patients.

Exploring the synergistic potential of probiotics and vitamin D to ameliorate acute TNBS-induced colitis in mice

Inflammatory Bowel Disease (IBD), either Crohn’s disease or Ulcerative Colitis, are diseases characterized by chronic inflammation of the gastrointestinal tract, disruption of mucosal barrier, gut dysbiosis and vitamin D deficiency. The use of probiotics or vitamin D supplements have been studied individually in different colitis models to determine their beneficial effects by increasing tight junction proteins such as occludin. However, the synergistic effects of combining these treatments to target tight junction expression are still unknown. Therefore, the objective of this research was to demonstrate the effcacy of probiotics and high dietary vitamin D to ameliorate colonic inflammation by increasing mucosal barrier integrity. We hypothesized that co-administration of a probiotic mixture with vitamin D would reduce colitis-induced inflammation by increasing tight junction expression. For the methodology, male and female C57BL/6 mice were divided into four treatment groups: Colitis+Vehicle (n=10), Colitis+Probiotic (n=10), Colitis+Vitamin D (n=11), Colitis+Probiotic+Vitamin D (n=7). Animals received seven days of pretreatment with Vivomixx probiotics in water, high vitamin D (5IU/g) in food, or both. On day 7, animals were anesthetized lightly, and colitis induction was done by intracolonic administration of 0.1mL of 4mg TNBS in 30% ethanol. Water, food, and body weight were monitored daily. Animals were sacrificed on day ten, the colonic tissue was removed and assessed for inflammation then stained for occludin expression by immunofluorescence, and probiotic colonization was confirmed within fecal samples by RT-PCR amplification of S. Thermophilus gene. Results indicate that all animals decreased weight after colitis induction, but only animals receiving probiotic had a slight recovery by day 10. Animals receiving the probiotic mixture had higher S. Thermophilus expression in fecal samples compared to vehicle (p<0.001) indicating appropriate colonization. A significant reduction in macroscopic damage score (3.92 vs. 7.42, p<0.05) and microscopic score (3.42 vs 7.20, p<0.01) was found in animals with Probiotic+Vitamin D compared to vehicle. Although an increase in occludin expression was observed with probiotic administration it did not reach statistical significance. In conclusion, findings indicate a beneficial effect of combining probiotics and vitamin D on colonic tissue damage in an animal model of acute colitis but this did not impact the tight junction protein occludin. This work was supported by RISE (R25GM082406), G-RISE (T32GM144896), PRI MD Summer Program and Porter Physiology Development Fellowship. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A254 CANAGLIFLOZIN EXACERBATES CHEMICALLY INDUCED COLITIS WHEN COMBINED WITH A HIGH SUGAR DIET

Abstract Background Consumption of high-sugar diets exacerbates inflammation and hinders the healing process in animal models of acute colitis. Canagliflozin (CANA) is a sodium glucose cotransporter-2 (SGLT2) inhibitor primarily used for the management of type 2 diabetes and cardiovascular disease. CANA has demonstrated the ability to suppress human T cell and macrophage effector function and to improve inflammation in rat colitis models. Based on these findings, we hypothesized that CANA would mitigate the deleterious effects of a high sugar diet in a DSS colitis model through its effects on immune effector cells. Aims The aim of this study was to examine the effects of a high sugar diet and CANA administration on colonic inflammation in an animal model of acute colitis. Methods Adult wild-type male and female 129/SvEv mice were placed on standard chow or a high-sugar diet (HSD) containing 50% sucrose (AIN76A) ± CANA (10mg/kg) gavaged daily (n=4-6 for each group). Following three days on the respective diet, mice received 1.8-2% dextran sodium sulfate (DSS) in their drinking water for 5 days, followed by water alone for 4 days. Disease Activity Index (DAI) was computed daily based on changes in animal weight, stool consistency, and blood in stool. Colonic tissues were evaluated for histological changes, weight-to-length ratio, and cytokine levels using the MesoScale discovery platform. Results Mice on the HSD had increased severity of colitis compared with chow fed mice as evidenced by enhanced DAI, increased weight loss, and increased levels of colonic TNFα (pampersand:003C0.02). Response to CANA treatment was both sex and diet dependent. Contrary to our hypothesis, CANA treatment increased severity of colitis in male mice on the HSD as evidenced by increased DAI and delayed healing with increased enterocyte injury and increased levels of lamina propria neutrophils and lymphocytes. CANA treatment did not exacerbate disease severity in females on the HSD but did delay healing as evidenced by increased lamina propria neutrophils and lymphocytes and worse enterocyte injury. These effects were not observed in mice that were fed standard chow diets with CANA. Conclusions A high-sugar diet significantly exacerbates chemically induced colitis and delays healing. This effect is intensified when combined with CANA, especially in male mice. These findings indicate that effects of SGLT2 inhibitors on colonic inflammation can be modulated by both dietary intake and sex. Funding Agencies CCC

Buspirone Ameliorates Colon Inflammation in TNBS-Induced Rat Acute Colitis: The Involvement of TLR4/NF-kB Pathway.

Inflammatory bowel disease (IBD) is an inflammatory situation involving the whole digestive system. This illness includes ulcerative colitis and Crohn's disease. According to scientific research, the immune system plays an essential part in developing this disease. Recently, buspirone has been discovered to have anti-inflammatory properties. As a result, this research aims to see if buspirone provides anti-inflammatory effects in a rat model of TNBS-induced colitis. Control, TNBS, dexamethasone (2 mg/kg), and buspirone (5, 10, and 20 mg/kg) were randomly given to six groups of 36 male Wistar rats. Colitis was induced by intrarectal instillation of TNBS in all research groups except the control group, and rats were meliorated with dexamethasone and buspirone. Macroscopic and microscopic lesions appeared after colitis induction, while therapy with dexamethasone and buspirone significantly improved the lesions. TLR4 and pNF-κB expression were also enhanced during colitis induction. On the other hand, the administration of dexamethasone or buspirone resulted in a considerable reduction in their expression. Tissue TNF-α and MPO activity were enhanced after induction of colitis in terms of biochemical variables; however, administration of dexamethasone or buspirone reduced TNF-α and MPO activity. Eventually, in an animal model of severe colitis, buspirone displayed anti-inflammatory characteristics via lowering the TLR4/NF-ĸB signaling pathway's activity in an animal model of acute colitis.

The Keystone commensal bacterium Christensenella minuta DSM 22607 displays anti-inflammatory properties both in vitro and in vivo

Christensenellaceae is a family of subdominant commensal bacteria found in humans. It is thought to play an important role in gut health by maintaining microbial symbiosis. Indeed, these bacteria occur at significantly lower levels or are absent in individuals suffering from inflammatory bowel diseases (IBDs). Here, we explored if type species Christensenella minuta (strain: DSM 22607) could have the potential to help treat IBDs. We assessed key properties displayed by the bacterium using a combination of in vitro and in vivo assays. We found that while C. minuta is a strict anaerobe, it is also oxygen tolerant. Additionally, we observed that the species produces high levels of acetate and moderate levels of butyrate. We performed deep phenotyping using Biolog microarrays. Using human intestinal cell lines, we discovered that C. minuta demonstrated strong anti-inflammatory activity, resulting in reduced levels of proinflammatory IL-8 cytokines via the inhibition of the NF-κB signaling pathway. Furthermore, C. minuta protected intestinal epithelial integrity in vitro. Finally, in two distinct animal models of acute colitis, C. minuta prevented intestinal damage, reduced colonic inflammation, and promoted mucosal healing. Together, these results indicate that C. minuta has potent immunomodulatory properties, underscoring its potential use in innovative microbiome-based IBD biotherapies.

A biorefinery concept for the production of fuel ethanol, probiotic yeast, and whey protein from a by-product of the cheese industry.

Agroindustrial by-products and residues can be transformed into valuable compounds in biorefineries. Here, we present a new concept: production of fuel ethanol, whey protein, and probiotic yeast from cheese whey. An initial screening under industrially relevant conditions, involving thirty Kluyveromyces marxianus strains, was carried out using spot assays to evaluate their capacity to grow on cheese whey or on whey permeate (100 g lactose/L), under aerobic or anaerobic conditions, in the absence or presence of 5% ethanol, at pH 5.8 or pH 2.5. The four best growing K. marxianus strains were selected and further evaluated in a miniaturized industrial fermentation process using reconstituted whey permeate (100 g lactose/L) with cell recycling (involving sulfuric acid treatment). After five consecutive fermentation cycles, the ethanol yield on sugar reached 90% of the theoretical maximum in the best cases, with 90% cell viability. Cells harvested at this point displayed probiotic properties such as the capacity to survive the passage through the gastrointestinal tract and capacity to modulate the innate immune response of intestinal epithelium, both in vitro. Furthermore, the CIDCA 9121 strain was able to protect against histopathological damage in an animal model of acute colitis. Our findings demonstrate that K. marxianus CIDCA 9121 is capable of efficiently fermenting the lactose present in whey permeate to ethanol and that the remaining yeast biomass has probiotic properties, enabling an integrated process for the obtainment of whey protein (WP), fuel ethanol, and probiotics from cheese whey.Key points• K. marxianus-selected strains ferment whey permeate with 90% ethanol yield.• Industrial fermentation conditions do not affect selected yeast probiotic capacity.• Whey permeate, fuel ethanol, and probiotic biomass can be obtained in a biorefinery.

Protective effect of aqueous extract of Oroxylum indicum Linn. (root bark) against DNBS-induced colitis in rats

Objective:Aqueous root extract of Oroxylum indicum was evaluated in rats against dinitrobenzene sulfonic acid (DNBS) induced colitis.Materials and Methods:Rats were pre-treated orally for seven days and continued for four days after the induction of colitis with OIaq (100, 200, and 400 mg/kg) or vehicle. Colitis was induced by intracolonic instillation of 25 mg of DNBS per rat dissolved in 50% alcohol and 4 days later, the colonic mucosal damage was analyzed along with food intake, body weight, colon weight, spleen weight, histological damage, myeloperoxidase (MPO) activity, malondialdehyde (MDA) levels, reduced glutathione (GSH), and nitric oxide levels in colonic tissue homogenate.Results:Significant reduction in gross damage area, weight loss and increase in colonic and spleen weight were evident in test substance-pretreated animals’ dose dependently as compared to vehicle treated control. These effects were confirmed biochemically by a reduction in colonic myeloperoxidase activity, malondialdehyde levels, nitric oxide levels, and increase in reduced glutathione (GSH) levels. Furthermore, microscopic examination revealed diminution of inflammatory cell infiltration and submucosal edema in colon segments of rats treated with OIaq.Conclusion:The results demonstrate the protective effect of OIaq in the animal model of acute colitis possibly through an antioxidant, anti-lipoperoxidative or due to reduction in nitric oxide generation.

Role of tumor necrosis factor receptors in an animal model of acute colitis

TNF-alpha is known to play an important role in inflammatory bowel disease (IBD); however, the pathophysiological role of its receptors is still under study. Acute colitis was induced in rats by intracolonic administration of trinitrobenzene sulfonic acid (TNBS). Control rats received the ethanol vehicle. Rats were sacrificed 72 h later and samples of tissue and fluids were collected. There was a significant increase in the protein levels of sTNF-alpha, sTNFRI, and sTNFRII in the peritoneal fluid (PF) of experimental rats. TNF-alpha, TNFRI, and TNFRII mRNA expression was increased significantly in the colon of experimental animals compared to controls. TRAF3 and TRAF5 expression was also significantly higher, as was that of the adhesion molecules ICAM-1 and E-selectin. The increased expression of TNF-alpha, TNFRs, and the associated signaling factors in the colon of this rat model of IBD provides further evidence for their involvement in the promotion of inflammation and tissue damage. In addition, increased levels of sTNFRs in the PF of experimental rats—particularly sTNFRII—may be involved in the development of colitis by serving as a reservoir of TNF-alpha, and thus provide a novel therapeutic target for IBD.

Protective effect of Copaifera langsdorffii oleo-resin against acetic acid-induced colitis in rats

The oleo-resin from Copaifera langsdorffii (Leguminosae) was evaluated in rats on acetic acid-induced colitis. Rats were pretreated orally (15 and 2 h) or rectally (2 h) before the induction of colitis with copaiba oleo-resin (200 and 400 mg/kg) or vehicle (1 ml, 2% Tween 80). Colitis was induced by intracolonic instillation of a 2 ml of 4% (v/v) acetic acid solution and 24 h later, the colonic mucosal damage was analyzed for the severity of macroscopic colonic damage, myeloperoxidase (MPO) activity, and malondialdehyde levels. A significant reduction in gross damage score and in wet weight/length ratio of colonic tissue were evident in test substance-pretreated animals as compared to vehicle or oleo-resin alone-treated controls. This effect was confirmed biochemically by a reduction in colonic myeloperoxidase activity, the marker of neutrophilic infiltration, and by a marked decrease in malondialdehyde level, an indicator of lipoperoxidation. Furthermore, microscopical examination revealed the diminution of inflammatory cell infiltration, and submucosal edema in the colon segments of rats treated with copaiba oleo-resin. The data indicate the protective effect of copaiba oleo-resin in the animal model of acute colitis possibly through an antioxidant and or anti-lipoperoxidative mechanism.

Protective effect of Copaifera langsdorffii oleo-resin against acetic acid-induced colitis in rats

The oleo-resin from Copaifera langsdorffii (Leguminosae) was evaluated in rats on acetic acid-induced colitis. Rats were pretreated orally (15 and 2 h) or rectally (2 h) before the induction of colitis with copaiba oleo-resin (200 and 400 mg/kg) or vehicle (1 ml, 2% Tween 80). Colitis was induced by intracolonic instillation of a 2 ml of 4% (v/v) acetic acid solution and 24 h later, the colonic mucosal damage was analyzed for the severity of macroscopic colonic damage, myeloperoxidase (MPO) activity, and malondialdehyde levels. A significant reduction in gross damage score and in wet weight/length ratio of colonic tissue were evident in test substance-pretreated animals as compared to vehicle or oleo-resin alone-treated controls. This effect was confirmed biochemically by a reduction in colonic myeloperoxidase activity, the marker of neutrophilic infiltration, and by a marked decrease in malondialdehyde level, an indicator of lipoperoxidation. Furthermore, microscopical examination revealed the diminution of inflammatory cell infiltration, and submucosal edema in the colon segments of rats treated with copaiba oleo-resin. The data indicate the protective effect of copaiba oleo-resin in the animal model of acute colitis possibly through an antioxidant and or anti-lipoperoxidative mechanism.

Lexipafant (BB-882), a platelet activating factor receptor antagonist, ameliorates mucosal inflammation in an animal model of colitis.

To assess the anti-inflammatory action of lexipafant (BB-882), a platelet activating factor antagonist, in an animal model of acute colitis. An animal intervention study. Following the rectal instillation of formalin 0.75% into male New Zealand White (NZW) rabbits, 0.85 ml of aggregated immunoglobulin was administered i.v. Treatment groups (0.8 mg/kg, n = 6; 2.4 mg/kg, n = 13; 3.2 mg/kg, n = 10) were given bolus doses of BB-882 two-hourly i.v. (control group, n = 25). Rectal dialysis was performed before induction of colitis and sacrifice. Dialysate leukotriene B4 (LTB4), prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) levels were determined. Tissue was saved for histology and measurement of myeloperoxidase content. There was a dose-dependent improvement in macroscopic scores (2.4 and 3.2 mg/kg: P < 0.02, P < 0.001) and myeloperoxidase levels (3.2 mg/kg: P < 0.04). Dialysate LTB4 levels fell (2.4 and 3.2 mg/kg: P < 0.03, P < 0.02) as did PGE2 levels. TXB2 concentrations remained unaffected. The PAF receptor antagonist BB-882 shows efficacy in treating inflammation in an animal model of acute colitis as evidenced by a dose-dependent fall in macroscopic mucosal damage, neutrophil infiltration and reduced generation of inflammatory mediators.

5-Lipoxygenase inhibitors for the treatment of inflammatory bowel disease

The unique role of the enzyme 5-lipoxygenase (5-LO) in the production of leukotrienes (LTs) makes it a likely target for biochemical manipulation. The rationale for using 5-LO inhibitors for the treatment of inflammatory bowel disease (IBD) is based on the increased generation of LTs in the inflamed mucosa, LTB4 being the most potent chemotactic and chemokinetic metabolite of arachidonic acid. Furthermore, conventional drugs, such as corticosteroids, sulphasalazine, and 5-aminosalicylic acid, inhibit LT production and specific 5-LO inhibition accelerates healing in animal models of acute colitis. The compounds identified as 5-LO inhibitors can be divided into antioxidants, substrate-analogous, and a large miscellaneous group of inhibitors, where hydroxamic acids are potent and more selective inhibitors of 5-LO. The benzothiophene hydroxyurea, zileuton, is the first selective 5-LO inhibitor evaluated for the treatment of patients with IBD. An 800-mg oral dose of zileuton was shown to reduce LTB4, but not prostaglandin E2, concentrations by 75-85% in rectal dialysates from patients with active ulcerative colitis. The clinical efficacy of zileuton 800 mg b.i.d. has also been tested in a randomized, double-blind, placebo-controlled trial in similar patients. Zileuton significantly improved the symptom scores and the histology score, but not the sigmoidoscopy score, compared to pretreatment conditions and with response to placebo, the beneficial effects being most pronounced in patients not receiving concomitant sulphasalazine treatment. The mean inhibition of LTB4 in the target tissue of inflammation was 70%. The proof that any putative 5-LO inhibitor is blocking LT production is an important stage in assessing any such drug. The main disadvantage of existing new LT inhibitors relates to the high potency of LTs, and unless a higher level of inhibition can be achieved, endogenous LTs may still be present in sufficient amounts to produce their effects.