Acetic Acid-induced Colitis In Mice Research Articles

Umbelliprenin attenuates comorbid behavioral disorders in acetic acid-induced colitis in mice: mechanistic insights into hippocampal oxidative stress and neuroinflammation.

Inflammatory bowel disease (IBD) is often accompanied by psychiatric disorders. Emerging evidence suggests that neuroinflammation and oxidative stress contribute to the psychiatric symptoms associated with IBD. Umbelliprenin (UMB) possesses several pharmacological properties, including anti-inflammatory and antioxidant effects. This study aimed to investigate the protective effects of UMB on comorbid behavioral disorders in a mouse model of experimental colitis, focusing on its potential anti-neuroinflammatory and antioxidant activities. After inducing colitis with acetic acid, male NMRI mice were treated for 7 consecutive days with UMB, saline, or dexamethasone. Behavioral assessments included the forced swimming test (FST), splash test, open field test (OFT), and elevated plus maze (EPM). Histopathological changes in the colon were evaluated, and total antioxidant capacity (TAC), malondialdehyde (MDA) levels, and the expression of inflammatory genes (TNFα, IL1β, and TLR4) were measured in the hippocampus. Colitis was associated with increased immobility time in the FST, reduced entries and time spent in the open arms of the EPM, decreased grooming behavior in the splash test, and reduced time spent in the central zone of the OFT. Colitis also resulted in a reduction in TAC and an increase in MDA levels and inflammatory gene expression in the hippocampus. UMB treatment mitigated the behavioral disorders associated with colitis, reduced neuroinflammation and oxidative stress in the hippocampus, and alleviated histopathological alterations in the colon. In conclusion, UMB may reduce behavioral disorders induced by colitis by decreasing oxidative stress and neuroinflammation in the hippocampus.

Neuroimmune response and oxidative stress in the prefrontal cortex mediate seizure susceptibility in experimental colitis in male mice.

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder. Oxidative stress and inflammatory responses have a vital role in the pathophysiology of IBD as well as seizure. IBD is associated with extraintestinal manifestations. This study aimed to explore the relationship between colitis and susceptibility to seizures, with a focus on the roles of neuroinflammation and oxidative stress in acetic acid-induced colitis in mice. Forty male Naval Medical Research Institute mice were divided into four groups: control, colitis, pentylenetetrazole (PTZ), and colitis + PTZ. Colitis was induced by intrarectal administration of acetic acid, and seizures were induced by intravenous injection of PTZ 7 days postcolitis induction. Following the measurement of latency to seizure, the mice were killed, and their colons and prefrontal cortex (PFC) were dissected. Gene expression of inflammatory markers including interleukin-1β, tumor necrosis factor-alpha, NOD-like receptor protein 3, and toll-like receptor 4, as well as total antioxidant capacity (TAC), malondialdehyde (MDA), and nitrite levels were measured in the colon and PFC. Histopathological evaluations were performed on the colon samples. Data were analyzed by t-test or one-way variance analysis. Colitis decreased latency to seizure, increased gene expression of inflammatory markers, and altered levels of MDA, nitrite, and TAC in both the colon and PFC. Simultaneous induction of colitis and seizure exacerbated the neuroimmune response and oxidative stress in the PFC and colon. Results concluded that neuroinflammation and oxidative stress in the PFC at least partially mediate the comorbid decrease in seizure latency in mice with colitis.

Development of trans-Chalcone loaded pectin/casein biodegradable microcapsules: Efficacy improvement in the management of experimental colitis

Improved therapies for inflammatory bowel diseases are sorely needed. Novel therapeutic agents and the development of controlled release systems for targeted tissue delivery are interesting approaches to overcome these barriers. We investigated the activity of trans-chalcone (T) in acetic acid-induced colitis in mice and developed, characterized, and determined the therapeutic effect of pectin/casein polymer microcapsules containing T (MT) in a colitis mouse model. In vitro, compound release was achieved in simulated intestinal fluid but not in the simulated gastric fluid. In vivo, since T at the dose of 3 mg/kg but not 0.3 mg/kg ameliorated colitis, we next tested the effects of MT at 0.3 mg/kg (non-effective dose). MT, but not free T at 0.3 mg/kg, significantly improved colitis outcomes such as neutrophil recruitment, antioxidant capacity, cytokine production, and NF-kB activation. This translated into reduced macro and microscopic damage in the colon. T release from the microcapsules is mediated by a pH-dependent and pectinase-regulated mechanism that provide controlled and prolonged release of T. Moreover, MT lowered the required dose for T therapeutic effect, indicating that could be a suitable pharmaceutical approach to colitis treatment. This is the first demonstration that T or MT is effective at reducing the signs of colitis.

THE EFFECT OF SALVIA FRUTICOSA WATER EXTRACT IN ACETIC-ACID-INDUCED COLITIS IN MICE

Inflammatory bowel disease (IBD) including Ulcerative colitis (UC) and Crohn’s disease, is a chronic condition of the intestine characterized by an uncontrolled inflammatory response. Current biologic treatments developed to treat IBD are expensive and associated with significant side effects; thus, alternative approaches are required. Recently, herbal concoctions have emerged as promising intervention. This study investigates the protective effects of Salvia fruticosa (SF) against acetic acid-induced colitis in mice, a model of human inflammatory bowel disease (IBD). Mice were divided into four groups (n=3). IBD was induced with acetic acid (6%). SF was administered by gavage at 1.5ug/kg mimicking folk medicine. SF treatment was given for 2, 4 & 6 days. After treatment, colons were collected for colonic biochemical markers, and histopathological evaluation. SF treatment induced enhancement in the colon’s structure and decreased ulcerations and inflammation. It significantly decreased pro-inflammatory cytokines TNF-α, IL-17 by 2.1-fold and 0.9-fold respectively at day2 and 6 and IL-6 by 2.8-fold at day 2 & 1.7-fold at day 6. Also, pro-inflammatory cytokine INF-γ showed a significant 22-fold decrease at day2 in SF-treated colitic group. Moreover, Myeloperoxidase (MPO) and Malondialdehyde (MDA) levels decreased showing the anti-oxidant property of the extract. Anti-oxidant Glutathione (GSH) level and anti-inflammatory cytokine IL-10, remained at normal levels while an increase by 0.9-fold at day 2 and 0.5-fold at day 6 in anti-inflammatory cytokine TGF-β in healthy SF-treated groups was significant. Hence, Salvia fruticosa exerts an anti-inflammatory and anti-oxidant effects against IBD as well as it help healing colon ulcers and maintain its architecture.

Anethole Ameliorates Acetic Acid-Induced Colitis in Mice: Anti-Inflammatory and Antioxidant Effects.

Anethole has possessed anti-inflammatory and antioxidant responses in numerous studies. Oxidative stress has a pivotal role in the pathophysiology of colitis. The current study is designed to determine the effect of anethole on acetic acid-induced colitis in mice in view of its possible anti-inflammatory and antioxidant properties. In this study, 48 mice were grouped into 6 groups (n = 8), and colitis was induced with 0.2 ml of 7% acetic acid. Mice received intraperitoneally (i.p.) for 7 constant days normal saline and/or anethole at doses of 31.25, 62.5, 125, and 250 mg/kg, respectively. After treatments, the colon was dissected out, and histopathological changes, expression of inflammatory genes (IL-1β, TNF-α, and TLR4), and evaluation of malondialdehyde (MDA) levels and total antioxidant capacity (TAC) were assessed. The results showed that colitis is associated with edema and inflammatory responses in all layers and severe damage to the epithelium of the colon. Colitis causes a decrease in TAC, an increase in MDA levels, and an increase in inflammatory genes in the colon. Findings determined that anethole ameliorated the adverse effects of acetic acid-induced colitis in the colon. It is concluded that anethole, partially at least, possessed protective effects in acetic acid-induced colitis in mice through attenuation of oxidative stress and inflammatory response.

Ameliorative effect of Leiurus quinquestriatus venom on acetic acid-induced colitis in mice

Scorpion venom has anti-microbial, anti-cancer, and anti-malarial activities. Also, it has an effective role in the treatment of autoimmune disease and as a pain-relieving agent. Ulcerative colitis (UC) is a chronic deteriorating inflammatory bowel disease. It is urgent to find new and safe products with lesser side effects. This study aimed to use scorpion Leiurus quinquestriatus venom (L.Q venom) for the first time as an anti-inflammatory agent to ameliorate the colon condition after UC induction. Also, to detect the effect of the combinatorial treatment of L.Q venom and Meslazine (Mes) drug. Fifty male albino mice were divided into 5 groups (n = 10); the first group (Gp1) served as a negative control. UC was induced in Gp2, Gp3, Gp4 and Gp5 by 4% acetic acid. Gp2 served as a positive control. After 24 h of UC induction, Gp3 was injected with L.Q venom (3.12 µg/kg) inter peritoneal (i.p), and Gp4 was administered orally by Mes (100 mg/kg). Gp5 was treated with L.Q venom and Mes as in Gp3 and Gp4. All treatments were taken for 7 consecutive days. Disease activity index (DAI), the macroscopic and microscopic investigations, TREM-1, MMP-9, caspase-3, NO, MPO levels were measured. Moreover, COX-2 and IL-22 were investigated in colonic tissue and TLR-9 expression was determined by RT-PCR. The results showed that all previous mentioned parameters were increased in the positive control group (Gp2), however, treatment with L.Q venom (Gp3) decreased these parameters. Interestingly, the combinatorial treatment with L.Q venom/Mes showed an additive effect that was able to ameliorate the physiological, biochemical and histopathological changes that were induced in UC-mice. Collectively, the L.Q venom showed a promising anti-inflammatory effect, which could be used to ameliorate the side effects of UC, either alone or in combination with Mes.

Gelling polysaccharide from Chondrus armatus and its oligosaccharides: The structural peculiarities and anti-inflammatory activity

Structural peculiarities of low molecular weight (LMW) sample obtained by mild acid hydrolysis of κ-carrageenan from Chondrus armatus was investigated by a rapid mass spectrometric method. The selected conditions allowed avoiding excess destruction of 3,6-AnGal residues that was shown by using tandem (MS/MS) mode. Main oligosaccharide fraction with molecular weight 2.3kg/mol, obtained by mild acid hydrolysis was chosen for the analysis. It was shown that fragments with even degree of polymerization (DP) were mostly built of (-G4S-DA-)n repeating unit, n=1–5. Some fragments with odd DP were shown to contain -DA2S- insertions, being the fragments of ι-type blocks, which were randomly distributed along the polysaccharide chain as single insertions. The anti-inflammatory activity (on acetic acid-induced colitis in mice) of the initial polymer and its derivatives was studied. The anti-inflammatory effect of the polymer was observed at a dose of 5mg/kg. Polysaccharide decreased the degree of colon damage more than twice and area of damage in 40%.

Quercetin-Loaded Microcapsules Ameliorate Experimental Colitis in Mice by Anti-inflammatory and Antioxidant Mechanisms

Quercetin (1) is an anti-inflammatory and antioxidant flavonoid. However, the oral administration of 1 did not lead to beneficial effects in experimental animal colitis models, which involve cytokines and oxidative stress. A possible explanation is that the absorption profile of 1 prevents its activity. Therefore, it was reasoned that the controlled release of 1 would improve its therapeutic effect. Thus, the therapeutic effect and mechanisms of 1-loaded microcapsules in acetic acid-induced colitis in mice were evaluated. Microcapsules were prepared using pectin/casein polymer and 1. The oral administration of 1-loaded microcapsules decreased neutrophil recruitment, attenuated histological alterations, and reduced macroscopical damage, edema, and IL-1β and IL-33 production in the colon samples. Microcapsules loaded with 1 also prevented the reduction of anti-inflammatory cytokine IL-10 and the antioxidant capacity of the colon. These preclinical data indicate that pectin/casein polymer microcapsules loaded with 1 improved the anti-inflammatory and antioxidant effects of 1 compared to the nonencapsulated drug. Therefore, quercetin seems to be a promising active molecule in inflammatory bowel disease if provided with adequate controlled release.

Protective Effect of Comaruman, a Pectin of Cinquefoil Comarum palustre L., on Acetic Acid-Induced Colitis in Mice

The efficacy of comaruman CP, a pectin of marsh cinquefoil Comarum palustre L., was investigated using a model of acetic acid-induced colitis in mice. Mice were administered comaruman CP orally 2 days prior to rectal injection of 5% acetic acid and examined for colonic damage 24 hr later. Colonic inflammation was characterized by macroscopical injury, higher levels of myeloperoxidase activity, enhanced vascular permeability, and diminution of colonic mucus. Oral administration of comaruman CP was found to prevent progression of colitis. Colonic macroscopic scores and the total square of damage were significantly reduced in mice treated with CP compared with the vehicle-treated colitis group. Peroral pretreatment of mice with comaruman CP was shown to decrease tissue myeloperoxidase activity in colons compared with the colitis group. Comaruman CP was found to stimulate production of mucus by colons of normal and colitis mice. Comaruman CP decreased the inflammatory status of normal mice as elicited by reduction of vascular permeability and adhesion of peritoneal neutrophils and macrophages. Thus, a preventive effect of comaruman on acetic acid-induced colitis in mice was detected. Reduction of neutrophil infiltration and enhancement of colon-bound mucus may be implicated in the protective effect of comaruman.

Preventive effect of a pectic polysaccharide of the common cranberryVaccinium oxycoccosL. on acetic acid-induced colitis in mice

To study isolation and chemical characterization of pectin derived from the common cranberry Vaccinium oxycoccos L. (oxycoccusan OP) and the testing of its preventive effect on experimental colitis. Mice were administrated orally with OP two days prior to a rectal injection of 5% acetic acid and examined for colonic damage 24 h later. Colonic inflammation was characterized by macroscopical injury and enhanced levels of myeloperoxidase activity measured spectrophotometrically with o-phenylene diamine as the substrate. The mucus contents of the colon were determined by the Alcian blue dye binding method. Vascular permeability was estimated using 4% Evans blue passage after i.p. injection of 0.05 mol/L acetic acid. In the mice treated with OP, colonic macroscopic scores (1.1+/-0.4 vs 2.7, P<0.01) and the total square area of damage (10+/-2 vs 21+/-7, P<0.01) were significantly reduced when compared with the vehicle-treated colitis group. OP was shown to decrease the tissue myeloperoxidase activity in colons (42+/-11 vs 112+/-40, P<0.01) and enhance the amount of mucus of colitis mice (0.9+/-0.1 vs 0.4+/-0.1, P<0.01). The level of colonic malondialdehyde was noted to decrease in OP-pretreated mice (3.6+/-0.7 vs 5.1+/-0.8, P<0.01). OP was found to decrease the inflammatory status of mice as was determined by reduction of vascular permeability (161+/-34 vs 241+/-21, P<0.01). Adhesion of peritoneal neutrophils and macrophages was also shown to decrease after administration of OP (141+/-50 vs 235+/-37, P<0.05). Thus, a preventive effect of pectin from the common cranberry, namely oxycoccusan OP, on acetic acid-induced colitis in mice was detected. A reduction of neutrophil infiltration and antioxidant action may be implicated in the protective effect of oxycoccusan.

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.

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

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