Dextran Sulfate Sodium In Rats Research Articles

Chicoric acid enhances the antioxidative defense system and protects against inflammation and apoptosis associated with the colitis model induced by dextran sulfate sodium in rats.

Although several anticolitic drugs are available, their application is associated with numerous side effects. Chicoric acid (CA) is a hydroxycinnamic acid found naturally in chicory (Cichorium intybus), purple coneflower (Echinacea purpurea), and basil with numerous health benefits, such as antioxidative and anti-inflammatory activities. Here, the potential anticolitic efficiency of CA against dextran sulfate sodium (DSS)-induced colitis in rats was examined in rats. Animals were randomly assigned to the following five groups: control, CA (100mg/kg body weight), DSS [(DSS); 4% w/v], CA + DSS (100mg/kg), and the 5-aminosalicylic acid (100mg/kg) + DSS group. The obtained data revealed that CA significantly prevented the shortening of colon length. Meanwhile, the oxidative stress-related enzymes were increased, while malondialdehyde and nitric oxide, were markedly decreased significantly by CA. The results also indicated that CA administration decreased significantly the pro-apoptogenic indices (Bax and caspase-3) and enhanced significantly Bcl-2, the anti-apoptogenic protein. Moreover, DSS caused a significant elevation of pro-inflammatory mediators, including interleukin-1β, tumor necrosis factor-α, myeloperoxidase, cyclooxygenase II, prostaglandin E2, and peroxisome proliferator-activated receptor gamma. Interestingly, these changes were significantly decreased following the CA administration. At the molecular level, CA supplementation has increased significantly the expression level of nuclear factor erythroid 2-related factor-2 (Nrf2) and decreased the expressions of nitric oxide synthase and mitogen-activated protein kinase 14. CA has been determined to significantly lessen DSS-induced colitis by activating Nrf2 and its derived antioxidant molecules and suppressing inflammation and apoptosis cascades associated with the development of colitis; suggesting that CA could be used as an alternative naturally-derived anticolitic agent.

Assessing acute colitis induced by dextran sulfate sodium in rats and its impact on gastrointestinal fluids.

Dextran sulfate sodium (DSS) is commonly used to induce colitis in rats. While the DSS-induced colitis rat model can be used to test new oral drug formulations for the treatment of inflammatory bowel disease, the effect of the DSS treatment on the gastrointestinal tract has not been thoroughly characterized. Additionally, the use of different markers to assess and confirm successful induction of colitis is somewhat inconsistent. This study aimed to investigate the DSS model to improve the preclinical evaluation of new oral drug formulations. The induction of colitis was evaluated based on the disease activity index (DAI) score, colon length, histological tissue evaluation, spleen weight, plasma C-reactive protein, and plasma lipocalin-2. Furthermore, the study investigated how the DSS-induced colitis affected the luminal pH, lipase activity, and concentrations of bile salts, polar lipids, and neutral lipids. For all evaluated parameters, healthy rats were used as a reference. The DAI score, colon length, and histological evaluation of the colon were effective disease indicators in DSS-induced colitis rats, while spleen weight, plasma C-reactive protein, and plasma lipocalin-2 were not. The luminal pH of the colon and bile salt- and neutral lipid concentrations in regions of the small intestine were lower in DSS-induced rats compared to healthy rats. Overall, the colitis model was deemed relevant for investigating ulcerative colitis-specific formulations.

In Vitro Antioxidant, Anti-inflammatory, and In Vivo Anticolitis Effects of Combretin A and Combretin B on Dextran Sodium Sulfate-Induced Ulcerative Colitis in Mice.

Combretum fragrans (Combretaceae) is a Cameroonian medicinal plant containing various secondary metabolites and traditionally used for the treatment of several pathologies. Two cycloartane-type triterpenes, Combretin A and Combretin B, were isolated from this plant. This study was aimed at evaluating the anti-inflammatory, antioxidant, and anticolitis effects of these compounds. In vitro anti-inflammatory properties were evaluated by inhibition of cyclooxygenase, 5-lipoxygenase, and denaturation of the protein; antioxidant properties were assessed by using 1,1-diphenyl-2-picrylhydrazyl (DPPH), (2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid)) ABTS•+, capacity tests ferric reducing antioxidant (FRAP), and trapping nitric oxide. For in vivo analysis, we used the model of ulcerative colitis induced by Dextran Sulfate Sodium (DSS). Studies of the anti-inflammatory activity showed that Combretin A and Combretin B had maximal inhibitory activity on cyclooxygenase (71.92% and 89.59%), 5-lipoxygenase (76.68% and 91.21%), and protein denaturation (63.93% and 87.78%). Antioxidant activity on DPPH, ABTS•+, ferric reducing antioxidant capacity (FRAP), and nitric oxide scavenging showed that Combretin A and Combretin B showed good antioxidant activities. These compounds significantly reduced the signs of DSS-induced colitis in the treated animals by preventing the weight loss of the animals, by significantly reducing the disease activity index, improving the condition of the stool, preventing the reduction of the length of the colon, and preventing the degradation of the colon. This study revealed that Combretin A and Combretin B have anti-inflammatory, antioxidant, and curative properties against colitis experimentally induced by DSS in rats.

Live and heat-killed cells of Lactobacillus plantarum Zhang-LL ease symptoms of chronic ulcerative colitis induced by dextran sulfate sodium in rats

• Chronic UC rats Gavaged with live or heat-killed cells were of 100% survival rate. • Live and heat-killed cells increased intestinal flora diversity of Chronic UC rats. • Live and heat-killed cells reduced intestinal permeability of Chronic UC rats. • Heat-killed cells were more effective against chronic UC in rats than live cells. Controversial results were yielded in some studies on the effects of Lactobacillus on ulcerative colitis (UC). In this work, we evaluated the effect of live or heat-killed Lactobacillus plantarum Zhang-LL cells and cell supernatants on dextran sulfate sodium (DSS)-induced UC in rats. The tested subjects were gavaged to rats for 7 days, and then 5% was used DSS repeatedly to induce chronic UC. The results of a 42-day experiment, indicated consistently and significantly that Both living and heat-killed cells of L. plantarum Zhang-LL could down-regulate content of pro-inflammatory cytokines (TNF-α, INF-γ) in serum, reduce intestinal permeability by increasing the expression of tight junction proteins zo-1, claudin-1 and occludin in colon tissue, and maintain intestinal microbiota stability by increasing intestinal microbiota diversity to alleviate the symptoms of chronic UC in rats with 100% survival rate. Of concern is, the heat-killed cells of L. plantarum Zhang-LL were more effective against DSS-induced chronic UC in rats.

Tripterygium wilfordii polyglycosidium ameliorates pouchitis induced by dextran sulfate sodium in rats

BackgroundThe aim of this study was to investigate the therapeutic effects of Tripterygium wilfordii polyglycosidium (TWP) to rats with dextran sulfate sodium (DSS)-induced pouchitis and its possible mechanism. MethodsSprague-Dawley rats underwent surgery of ileal pouch anal anastomosis (IPAA) and pouchitis was induced by DSS. Rats were randomly divided into no intervention (NI), normal saline (NS) and TWP groups. Rats were lavaged with normal saline (3ml/day in NS group) or TWP (12mg/kg/day in TWP group) for 7days. General conditions of animals and histopathological examinations were evaluated. Interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor (TNF)-α mRNA expression was measured. Levels of occludin and Zo-1 proteins were measured by immunohistochemistry. In addition, ALT and AST were assessed. ResultsTWP significantly attenuated the symptoms of pouchitis characterized by body weight loss, diarrhea, and bloody stool. Furthermore, TWP diminished histological damage compared with other groups. There was a significant reduction in levels of IL-1β, IL-6, and TNF-α, as well as an increase in IL-10 in the TWP group. The expression of tight junction proteins occludin and Zo-1 were increased in the TWP group. There were no statistical differences in serum ALT and AST among the three groups. ConclusionsTWP significantly ameliorated pouchitis and inhibited the production of IL-1β, IL-6, and TNF-α as well as increased the levels of IL-10, occludin, and Zo-1 protein in rats. These findings suggest TWP might be a potential therapeutic agent for patients with pouchitis.

Dextran Sulfate Sodium Enhances High Fat Diet Induced Insulin Resistance in Rat

High fat diet, obesity, and insulin resistance (IR) have been strongly associated with non-alcoholic fatty liver disease (NAFLD). Increasing evidence has shown that gut-liver axis plays a role in the pathogenesis of NAFLD. Dextran sulfate sodium (DSS) is known to increase intestinal permeability. This study investigates the hepatic effects of DSS in rats. Sprague Dawley rats were divided into 4 groups and fed with 4 different diets: control diet (Con, 15% of fat), high fat diet (HF, 60% of fat), control diet plus DSS (Con+D), and high fat diet plus DSS (HF+D). The food intakes and animal weights were measured twice a week. Fasting glucose and insulin were measured and IR HOMA was calculated. Rat glucose metabolism was also evaluated by intraperitoneal glucose tolerance test (IPGTT). The triglyceride (TG) levels in the livers were assayed after animals were sacrificed. Compared to control group, DSS treatment alone did not affect body weight, hepatic TG levels, IR HOMA, or IPGTT. Compared to the control (body weight = 495g), body weights in both HF (565g) and HF+D (554g) groups were increased while there was no significant difference between HF and HF+D groups. Similar results were obtained for hepatic TG levels. In terms of IR, HF and HF+D induced IR (HF/Con=1.8, p<0.05; HF+D/Con=2.5, p<0.05). Compared to HF alone, HF+D further enhanced IR (HF+D/HF=1.4, p<0.05). Similar results were observed in IPGTT assays. Ongoing studies will test if DSS can enhance steatohepatitis in HF fed rats. DSS enhances HF induced IR although DSS alone had no effects on IR. These results indicated that the intestinal microbes could have profound effects on liver functions.

Tu1637 Transplantaion of Human Fetal Membrane-Derived Mesenchymal Stem Cells Improves Severe Colitis Induced by Dextran Sulfate Sodium in Rats

Tu1637 Transplantaion of Human Fetal Membrane-Derived Mesenchymal Stem Cells Improves Severe Colitis Induced by Dextran Sulfate Sodium in Rats

Marginal Zinc Deficiency Exacerbates Experimental Colitis Induced by Dextran Sulfate Sodium in Rats

AbstractWe investigated the impact of Zn status on the maintenance of mucosal homeostasis. Rats were fed diets containing different amounts of Zn (30, 10, 5, <1 mg Zn/kg diet) for 21 d. Serum Zn concentrations were lower in rats fed marginally Zn-deficient (MZD; 5 mg Zn/kg diet) and severely Zn-deficient (<1 mg/kg) diets but not in those fed the marginally Zn-adequate diet (10 mg/kg) or the Zn-adequate (ZA; 30 mg/kg) group (P< 0.05). However, organ weights, colonic epithelial cell proliferation, and crypt fission did not differ between the MZD and ZA groups. We then evaluated whether MZD modulated dextran sulfate sodium (DSS)-induced colonic inflammation by administering 2% DSS to the MZD and ZA groups for 7 d. Myeloperoxidase activity and TNFa production increased in response to DSS in the MZD group (P <0.03). Colonic permeability in the 2 groups did not differ after DSS administration. In a culture experiment using isolated mesenteric leukocytes, TNFα production was higher (P< 0.05) and TNF receptor type I (TNFR1) expression was detected in culture medium containing 20 and 30μmol/L of Zn compared with culture medium lacking Zn supplementation. These results suggest that MZD exacerbated colitis by modulating the immune response through the impairment of TNFα production andTNFR1expression rather than through the impairment of epithelial barrier function.

Inhibitory Effects of Fermented Brown Rice on Induction of Acute Colitis by Dextran Sulfate Sodium in Rats

Although the pathogenic mechanisms of inflammatory bowel diseases are not fully understood, colonic microbiota may affect the induction of colonic inflammation, and some probiotics and prebiotics have been reported to suppress colitis. The inhibitory effects of brown rice fermented by Aspergillus oryzae (FBRA), a fiber-rich food, on the induction of acute colitis by dextran sulfate sodium (DSS) were examined. Feeding a 5% and 10% FBRA-containing diet significantly decreased the ulcer and erosion area in the rat colon stained with Alcian blue. In another experiment, 10% FBRA feeding decreased the ulcer index (percentage of the total length of ulcers in the full length of the colon) and colitis score, which were determined by macroscopic observation. It also decreased myeloperoxidase activity in the colonic mucosa. Viable cell numbers of Lactobacillus in the feces decreased after DSS administration and was reversely correlated with severity of colitis, while the cell number of Enterobacteriaceae increased after DSS treatment and was positively correlated with colitis severity. These results indicate that FBRA has a suppressive effect on the induction of colitis by DSS and suggest FBRA-mediated modification of colonic microbiota.

Possible role of mucosal mast cells in the recovery process of colitis induced by dextran sulfate sodium in rats

To clarify the role of mucosal mast cells in the lesion sites of colitis induced by dextran sulfate sodium (DSS) in rats, we investigated the histological changes and alterations relevant to mucosal mast cells in the spontaneous recovery process of colitis. Oral administration of 4% DSS solution for 11 days resulted in surface epithelial loss, crypt loss and goblet cell depletion in the rectal mucosa. A marked infiltration of inflammatory cells into the mucosa, which was consistent with a significant increase in myeloperoxidase (MPO) activity, was observed. In addition, mucosal mast cell number and rat mast cell protease (RMCP) I and II levels in the rectum increased at day 0 after DSS treatment, and most of the mucosal mast cells were degranulated. After replacing 4% DSS solution with water, re-epithelialization and restoration of goblet cells were observed at day 5 and day 10, respectively, but crypt damage was hardly recovered even at day 20. The elevated myeloperoxidase activity was significantly decreased from day 5 after DSS treatment. The increased number of mucosal mast cells was further elevated up to about 1.5-fold at day 10 and day 20 after DSS treatment and little degranulation was observed. In the spontaneous recovery process, the increased rat mast cell protease II level in the rectum was maintained for 20 days, while the increased rat mast cell protease I level was gradually decreased and recovered to control level. These results suggest that proliferated mucosal mast cells remained for 20 days, although most of infiltrated inflammatory cells disappeared in spontaneous recovery process of colitis. It may therefore be presumed that proliferated mucosal mast cells play a role in spontaneous recovery process of the colitis induced by DSS.

Involvement of kallikrein-kinin system in development of experimental ulcerative colitis induced by dextran sulfate sodium in rats

Involvement of kallikrein-kinin system in development of experimental ulcerative colitis induced by dextran sulfate sodium in rats

Involvement of kallikrein-kinin system in development of experimental ulcerative colitis induced by dextran sulfate sodium in rats

Involvement of kallikrein-kinin system in development of experimental ulcerative colitis induced by dextran sulfate sodium in rats

Effects of Chondroitin Sulfate on Colitis Induced by Dextran Sulfate Sodium in Rats

Chondroitin sulfate (CS) is currently marketed as a therapeutic drug for neurodynia, lumbago and arthrodynia. Recently, many clinical studies have demonstrated the therapeutic effects of orally administered CS against diseases with inflammation. Furthermore, these reports suggest CS plays an important role in the protection of the base of ulcers and has anti-inflammatory activity. We investigated the effects of CS against dextran sulfate sodium (DSS)-induced rat colitis. Rats were given 3% DSS solution for 10 days ad libitum. CS and 5-aminosalicylic acid (5-ASA) were orally administered daily. The doses of the CS groups were 20 or 100 mg /kg and that for the 5-ASA group was 100 mg /kg. Evaluations were made of bloody stools, areas of erosion and hematological data. CS improved the symptoms of bloody stools, erosion and increase of white blood cells. Especially, CS (100 mg/kg) group showed markedly more improvement than the 5-ASA group. We think that the major mechanism of the therapeutic effects of CS are the prevention of tissue damage by the protection of digestive mucosa and anti-inflammatory effects. Therefore, CS may have therapeutic value for alimentary tract diseases such as inflammatory bowel disease or ulcer.

Anti-neutrophil serum attenuates dextran sulfate sodium-induced colonic damage in the rat.

The role of neutrophils in experimental colonic damage induced by dextran sulfate sodium is uncertain. We test the hypothesis that neutrophils are of pathogenic significance and anti-neutrophil serum will attenuate the colonic damage induced by oral dextran sulfate sodium in rats. Rabbit anti-rat neutrophil serum (anti-neutrophil serum) or control rabbit serum was administered to, and circulating neutrophil count was monitored in, rats before and during feeding of dextran sulfate sodium or regular rat diet for 2 weeks. Histologic features of mucosal damage were evaluated in hematoxylin and eosin-stained proximal and distal colonic sections by a blinded observer. Oral dextran sulfate sodium induces weight loss, diarrhea, peripheral neutrophilia, and colonic damage. Anti-neutrophil serum induced neutropenia and significantly attenuated the weight loss, the neutrophil infiltration in the colon, and the mucosal necrosis and pathologic index in the distal colon. The data showing that anti-neutrophil serum attenuates distal colonic mucosal injury induced by dextran sulfate sodium support the hypothesis that neutrophils play a pathogenic role in this model of colonic mucosal damage.