Acetic Acid-induced Ulcerative Colitis In Rats Research Articles

Apigenin and Exposure to Low Dose Gamma Radiation Ameliorate Acetic Acid-Induced Ulcerative Colitis in Rats.

Ulcerative colitis (UC) is an inflammatory bowel disease involving chronic and recurring colon inflammation. Current management protocols are limited by adverse effects or short-term symptomatic relief. We aimed to investigate the possible therapeutic prospect of low dose gamma (γ) irradiation or apigenin treatment in acetic acid-induced UC in rats. Induction of UC was carried out by installation of acetic acid intra-rectally. One hour post-induction, rats received a sole dose of γ-radiation (0.5Gray) or were treated with apigenin (3mg/kg/day, peroral) for 7 successive days. Antioxidant and anti-inflammatory effects of both agents were assessed via determination of colon malondialdehyde (MDA), reduced glutathione (GSH), total nitrate/nitrite (NOx), mucosal addressin cell adhesion molecule-1 (MAdCAM-1), and interleukin-1beta (IL-1β) contents as well as myeloperoxidase (MPO) activity. Body weight (BW), colon weight/length (W/L) ratio, disease activity index (DAI), and histopathological changes were evaluated. Gamma irradiation and apigenin significantly ameliorated the acetic acid-induced biochemical and histopathological changes. Both therapeutic approaches significantly restored colon contents of the investigated biomarkers. They modulated BW, colon W/L ratio and DAI. This study proposes low dose γ-irradiation as a new therapeutic candidate for the management of UC. We also concluded that apigenin exhibited therapeutic benefits in UC management.

Dapagliflozin, an SGLT2 inhibitor, ameliorates acetic acid-induced colitis in rats by targeting NFκB/AMPK/NLRP3 axis.

The development of effective treatment strategies has been hindered by the complex pathogenesis of ulcerative colitis (UC). UC patients treated with current therapeutic approaches experienced either treatment failure or suffered excessive adverse reactions. Overactivity of NLRP3 inflammasome enhances inflammation, resulting in aggravation of colonic damage. We were interested in exploring, for the first time, the potential coloprotective effect of dapagliflozin (DPZ) on acetic acid-induced UC in rats in comparison with 5-ASA. DPZ improved histologic and macroscopic features of colon tissues and prolonged survival of UC rats. DPZ also prevented colon shortening and declined disease activity. Additionally, DPZ lessened colon tissue neutrophil content and improved antioxidant defense machinery. Further, DPZ specifically declined the colonic inflammatory marker IL-6 and upregulated the anti-inflammatory cytokine IL-10. The pyroptosis process is constrained in consequence of the repressed caspase-1 activity and caspase-1-dependent release of the bioactive cytokines IL-1β and IL-18. These protective effects might be attributed to that DPZ on the one hand, prevented the priming step (signal 1) of NLRP3 inflammasome activation as revealed by modulating NFκB/AMPK interplay and on the other hand, inhibited the activation step (signal 2) as indicated by interrupting NLRP3/caspase-1 signaling. Since DPZ was found to be safe and well tolerated by healthy volunteers with no evidence of hypoglycemia, it might show promise in the future management of UC. However, further investigations are warranted to confirm the reversal of injury and that the coloprotective effect is substantial.

The Therapeutic Effect of Shark Liver Oil in a Rat Model of Acetic Acid-Induced Ulcerative Colitis.

Ulcerative colitis (UC) is one of the most well-known types of inflammatory bowel disease that manifests as recurrent inflammation of rectum and colon. The goal of this study is to evaluate the protective effects of shark liver oil (SLO) on acetic acid-induced ulcerative colitis in rats. Eighty induced UC rats were randomly divided into ten equal groups and received the following treatments for seven days: 1 ml of normal saline rectally, 1 ml of gel base (carboxymethyl cellulose) rectally, 10 mg/kg of Asacol rectally, 10 mg/kg of mesalazine orally, 5% gel form of SLO rectally, 10% gel form of SLO rectally, 200 mg of SLO orally, and 400 mg of SLO orally. We examined the oxidative stress indices, histopathological features, and body weight changes, as well as the function of the liver and kidneys at the end of treatment. Administration of 10% rectal and 400 mg oral SLO resulted in a significant weight gain. Also, glutathione peroxidase activity was significantly higher in 5% and 10% SLO-treated groups, and elevated superoxide dismutase activity in rats that received 5% SLO was observed compared to negative control and Asacol groups. While no significant changes were observed in most of the kidney and liver function markers, higher levels of aspartate aminotransferase were detected in the group that received 400 mg SLO orally compared to negative control and Asacol groups. Many histopathological signs of improvement were observed in mesalazine, Asacol, and SLO groups. There were no significant changes detected in the mean rank among different groups. Our data indicate that SLO supplementation could improve the amelioration of acetic acid-induced UC in rats due to its antioxidant effects.

Effect of Sodium Cromoglycate on Acetic Acid-induced Ulcerative Colitis in Mice.

Ulcerative colitis (UC) is a type of inflammatory bowel disease that mainly involves the colon. Thus far, glucocorticoids and amino-salicylate have been the main treatment. To assess drugs with fewer side effects, this study evaluated the effects of sodium cromoglycate (SCG) on acetic acid-induced UC in rats. The treatment groups included SCG receivers (50 and 100 mg/kg, intra-orally) and sulfasalazine (SSZ) receivers (100 mg/kg, intra-orally). The colonic mucosal injury was assessed by clinical, macroscopic, and histopathological examinations. In the treatment groups with 50 and 100 mg/kg of SCG, the clinical activity score decreased to 2.67±0.18 and 1.73±0.21 (p<0.05), respectively, compared to the UC control group (3.21±0.31), and were higher than that of the group given the standard treatment of 100 mg/kg SSZ (1.10±0.09). The treatment groups with 50 and 100 mg/kg of SCG showed a lower clinical gross lesion score than the UC control group (2.91±0.28 and 2.10±0.43, vs. 4.49±0.61, p<0.05) and were higher than the standard group (0.95±0.18). Treatment with SCG (100 mg/kg) decreased the macroscopic scores significantly compared to the UC control group (p<0.05) on the 8th day. SCG (100mg/kg) decreased significantly the clinical activity score, gross lesion, and percentage-affected area compared to the UC controls on the 8th day.

Protective and Therapeutic Effects of Aloe Vera Gel on Ulcerative Colitis Induced by Acetic Acid in Rats.

Ulcerative colitis (UC) is a chronic intestinal inflammation. Common clinical symptoms are weight loss, diarrhea, ulcers, and inflammation. Aloe vera (AV) has several medicinal properties including antioxidant, anti-inflammatory analgesic, and improvement of gastric and skin ulcers. This study aimed to investigate the protective and therapeutic effects of AV gel on acetic acid-induced UC in rats. UC was induced in 48 rats by injection of 4% acetic acid into the rectum. Protective and treatment groups received treatments 7 days before and after the induction of colitis, respectively. The negative control group, the positive control group, and AV groups received distilled water, sulfasalazine, and 50 and 300 mg/kg of gel extract, respectively. Water and food intake and body weight changes were recorded. The extent of the mucosal ulcers, colon tissue thickening, and mucosal bleeding were scored by the Gerald classification system score (microscopy observations). Slides of tissues were prepared for pathologic assay using the modified Wallace method (macroscopic observations). The results of the macroscopic and microscopic examination showed protective and therapeutic effects of 50 mg/kg dose of AV on acetic acid-induced colitis in rats which reduces the inflammation, ulcers and tissue damage compared with negative control (p < 0.05). There were no significant changes in the amount of water and food intake, body weight changes, and colon weight in protective and treatment groups. Based on the results, AV gel could be used to improve the symptoms of UC, as well as prevent people who are susceptible to the UC.

Protective effect of Ferulago angulata (Schltdl.) Boiss. hydroalcoholic extract against acetic acid-induced colitis in rat: Role of pro-inflammatory cytokines

Background: Ulcerative colitis (UC) is a chronic recurrent inflammatory disease with unknown etiology. Ferulago angulata (Schltdl.) Boiss. has been proposed as an efficacious treatment for gastrointestinal ulcers and UC in the traditional Persian medicine. Objective: In the present study, we investigated the possible protective effect of F. angulata (Schltdl.) Boiss. hydroalcoholic extract (FAE) against acetic acid-induced UC in rats. Materials and Methods: The aerial parts of FAE (50, 100, and 200 mg/kg) were administered orally after acetic acid induced-inflammatory bowel disease. On the 3rd day, animals were euthanized by an overdose of ether inhalation and the abdomen was rapidly dissected for macroscopic, histological, and biochemical (tumor necrosis factor [TNF]-α, interleukin-1β [IL-1β]) analyses. Results: All doses of F. angulata (Schltdl.) Boiss. extract ameliorated acetic acid-induced macroscopic and microscopic scores, except for 50 mg/kg. Furthermore, our observations were accompanied by a significant (P Abbreviations Used: IBD: Inflammatory bowel disease; UC: Ulcerative colitis; CD: Crohn's disease; TNF-α: Tumor necrosis factor-α; IL-1β: Interleukin-1β; PMN: Polymorphonuclear; NO: Nitric oxide; FAE: Ferulago angulata (Schltdl.) Boiss. hydroalcoholic extract; COX: Cyclooxygenase.

Modulation of PPARγ and TNFα by emu oil and glycyrrhizin in ulcerative colitis.

Ulcerative Colitis (UC) is an inflammatory bowel disorder that affects colon and rectum. Treatments in many UC patients remain variably effective and are associated with considerable adverse effects. So the present study was undertaken to explore the antiinflammatory effects of emu oil, glycyrrhizin, and combination of emu oil and glycyrrhizin in acetic acid-induced UC in rats. UC was induced by intracolonic instillation of 5% acetic acid in rats. Emu oil and glycyrrhizin were orally administered to test groups. Severity of colitis was scored macroscopically and microscopically. The levels of myeloperoxidase and antioxidant enzymes namely catalase, superoxide dismutase and glutathione peroxidase were assessed spectrophotometrically. Expressions of PPARγ and TNFα were studied by real-time PCR. Acetic acid caused severe damage to colon and rectum. Emu oil and glycyrrhizin were found to significantly reduce macroscopic and microscopic lesions and decrease levels of myeloperoxidase. There was a significant improvement of antioxidant levels in treatment groups compared to acetic acid group. Combination of emu oil and glycyrrhizin showed a markedly greater modulation of PPARγ and TNFα expression than emu oil and glycyrrhizin when administered alone. Combination of emu oil and glycyrrhizin might have had synergistic effects in regulating PPARγ and TNFα. Further studies on mechanism of action of emu oil and glycyrrhizin combination would pave the way to define possibility of this combination as effective in the management of UC.