Monocolonization of Germ-Free Mice withBacteroides fragilisProtects against Dextran Sulfate Sodium-Induced Acute Colitis

Ulcerative colitis is inflammatory conditions of the colon caused by interplay of genetic and environmental factors. Previous studies indicated that the gut microflora may be involved in the colonic inflammation.Bacteroides fragilis(BF) is a Gram-negative anaerobe belonging to the colonic symbiotic. We aimed to investigate the protective role ofBFin a colitis model induced in germ-free (GF) mice by dextran sulfate sodium (DSS). GF C57BL/6JNarl mice were colonized withBFfor 28 days before acute colitis was induced by DSS.BFcolonization significantly increased animal survival by 40%, with less reduction in colon length, and decreased infiltration of inflammatory cells (macrophages and neutrophils) in colon mucosa following challenge with DSS. In addition,BFcould enhance the mRNA expression of anti-inflammatory-related cytokine such as interleukin 10 (IL-10) with polymorphism cytokineIL-17and diminish that of proinflammatory-related tumor necrosis factorαwith inducible nitric oxide synthase in the ulcerated colon. Myeloperoxidase activity was also decreased inBF-DSS mice. Taking these together, theBFcolonization significantly ameliorated DSS-induced colitis by suppressing the activity of inflammatory-related molecules and inducing the production of anti-inflammatory cytokines.BFmay play an important role in maintaining intestinal immune system homeostasis and regulate inflammatory responses.

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Treatment of Dextran Sulfate Sodium-Induced Colitis with Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Inhibitor MI-2 Is Associated with Restoration of Gut Immune Function and the Microbiota

Infection and Immunity ◽

10.1128/iai.00091-18 ◽

2018 ◽

Vol 86 (12) ◽

Cited By ~ 7

Author(s):

Kyung Won Lee ◽

Minseok Kim ◽

Chang Hoon Lee

Keyword(s):

Ulcerative Colitis ◽

Lymphoid Tissue ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Inflammatory Responses ◽

Fecal Microbiota ◽

Intestinal Microbiome ◽

Diverse Populations ◽

Necrosis Factor Alpha ◽

Intestinal Immune System

ABSTRACT Disruption of the healthy intestinal microbiome and homeostasis of the intestinal immune system, which are closely interactive, are two key factors for ulcerative colitis. Here, we show that MI-2, a selective inhibitor of mucosa-associated lymphoid tissue lymphoma translocation-1 (MALT1), alleviated excessive inflammatory responses and was associated with restoration of healthy intestinal microbiome in mice suffering from dextran sulfate sodium (DSS)-induced colitis. We found that the diversity of intestinal microbiome of mice with DSS-induced colitis was significantly lower than that of healthy mice. However, MI-2 treatment in mice with DSS-induced colitis resulted in restored microbially diverse populations. To understand the possibility of the beneficial effect of the restored microbially diverse populations of MI-2-treated mice with DSS-induced colitis, we showed that inserting fecal microbiota from MI-2-treated mice with DSS-induced colitis and healthy control mice into mice with DSS-induced colitis could alleviate symptoms of colitis. The possibility of MI-2 treatment in DSS-induced colitis, associated with restoration of healthy microbially diverse populations in addition to reshaping host immune modulating capacity by reducing inflammatory cytokines (tumor necrosis factor alpha, interleukin-1β [IL-1β], IL-17α, and IL-22), may be considered therapeutic for ulcerative colitis.

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Galectin-1 exhibits a protective effect against hepatotoxicity induced by dextran sulfate sodium in mice

Human & Experimental Toxicology ◽

10.1177/0960327119891224 ◽

2019 ◽

Vol 39 (4) ◽

pp. 423-432

Author(s):

P Arda-Pirincci ◽

O Sacan ◽

C Ozal-Coskun ◽

G Aykol-Celik ◽

O Karabulut-Bulan ◽

...

Keyword(s):

Cell Proliferation ◽

Antioxidant System ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Liver Toxicity ◽

Interleukin 10 ◽

Control Group ◽

Protective Agent ◽

Necrosis Factor Alpha ◽

Anti Inflammatory

Galectin-1 is an important mediator that regulates the T-cell-mediated immune response. It has many other biological functions such as cell growth, immunomodulation, and wound healing. The aim of this study was to reveal the role of galectin-1 on liver morphology, cell proliferation, apoptosis, inflammatory and anti-inflammatory mediators, oxidative stress, and antioxidant system in colitis-mediated hepatotoxicity induced by dextran sulfate sodium (DSS). In the present study, adult mice were divided into four groups: The control group intraperitoneally injected with phosphate buffer saline (I), the group which was orally administered with DSS (II), the control group which was injected with galectin-1 (III), and the group which was given DSS and galectin-1 (IV). DSS administration caused degenerative changes and diffuse necrotic damage, an increase in caspase-3 and cyclooxygenase-2 expression, the levels of lipid peroxidation and tumor necrosis factor-alpha, lactate dehydrogenase, and myeloperoxidase activities, and a decrease in cell proliferation, interleukin-10 levels, and antioxidant system parameters in liver tissues. Treatment of DSS group with galectin-1 reversed these effects and prevented liver damage. This study showed that galectin-1 has proliferative, antiapoptotic, anti-inflammatory, and antioxidant effects against DSS-induced liver injury in mice. It is expected considering all results of this study that galectin-1 may be useful as a protective agent against liver toxicity.

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Standardized Fraction of Turbinaria ornata Alleviates Dextran Sulfate Sodium-Induced Chronic Colitis in C57BL/6 Mice via Upregulation of FOXP3+ Regulatory T Cells

Biomolecules ◽

10.3390/biom10101463 ◽

2020 ◽

Vol 10 (10) ◽

pp. 1463

Author(s):

Na-Hyun Kim ◽

Seon Min Lee ◽

Yun Na Kim ◽

You-Jin Jeon ◽

Jeong-Doo Heo ◽

...

Keyword(s):

T Cell ◽

Inflammatory Cytokine ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

T Cell Subsets ◽

Myeloperoxidase Activity ◽

Chronic Colitis ◽

Turbinaria Ornata ◽

Tnf Α ◽

Anti Inflammatory

Turbinaria ornata is a tropical brown algae (seaweed) known to have anti-inflammatory properties. In this study, we analyzed T. ornata extract (TOE) using liquid chromatography quadrupole time of flight mass spectrometry (LC-QTOF-MS) and nuclear magnetic resonance (NMR) and evaluated the in vivo efficacy of TOE against dextran sulfate sodium-induced chronic colitis in C57BL/6 mice. The bioactive fraction of TOE was administered orally daily for 6 weeks to mice under different treatments normal, colitis, and colitis + conventional drug (5-aminosalicylic acid, 5-ASA). Regarding clinical manifestation, the disease activity index and colon length of the colitis + TOE group were significantly reduced compared to those of the colitis group. The results of myeloperoxidase activity and histopathological examination showed similar results. Western blot analysis of colon tissues revealed that cyclooxygenase-2, tumor necrosis factor alpha (TNF-α), and phosphorylated signal transducer and activator of transcription-3 (p-STAT3) were significantly decreased in the colitis + 5-ASA group, whereas forkhead box P3 (FOXP3) was increased. qPCR results showed changes in T cell subsets; the administration of TOE upregulated regulatory T cell (Treg) expression, although T helper 17 cell (Th17) expression did not change significantly. Interestingly, the colitis + TOE group showed high levels of both Th1 and Th2 transcription factors, but the secreted cytokine interferon (IFN)-γ and interleukin (IL)-4 remained unchanged and somewhat reduced. Additionally, TNF-α gene expression was significantly reduced in the colitis + TOE group. IL-6 mRNA levels were also decreased, although not significantly. Four compounds were structurally elucidated using 1D- and 2D-NMR spectroscopy, and five compounds were fully identified or tentatively characterized using LC-QTOF-MS. In conclusion, TOE could alleviate chronic colitis via upregulation of Foxp3+ Treg cells and production of the anti-inflammatory cytokine IL-10, which directly inhibits macrophages and pro-inflammatory cytokine synthesis, leading to reduced colitis.

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Japanese rice wine (Sake)-derived pyroglutamyl peptides have anti-inflammatory effect on dextran sulfate sodium (DSS)-induced acute colitis in mice

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2018.04.465 ◽

2018 ◽

Vol 120 ◽

pp. S141

Author(s):

Sayori Wada ◽

Tamami Kiyono ◽

Shoko Fukunaga ◽

Wataru Aoi ◽

Yuji Naito ◽

...

Keyword(s):

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Rice Wine ◽

Acute Colitis ◽

Anti Inflammatory ◽

Inflammatory Effect

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Oxyresveratrol Ameliorates Dextran Sulfate Sodium-Induced Colitis in Rats by Suppressing Inflammation

Molecules ◽

10.3390/molecules26092630 ◽

2021 ◽

Vol 26 (9) ◽

pp. 2630

Author(s):

Jiah Yeom ◽

Seongho Ma ◽

Jeong-Keun Kim ◽

Young-Hee Lim

Keyword(s):

Inflammatory Cytokine ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Intestinal Inflammation ◽

Mucus Layer ◽

Beneficial Effects ◽

Intestinal Mucus ◽

Anti Inflammatory ◽

Apoptotic Effects ◽

Intestinal Mucus Layer

Colitis causes destruction of the intestinal mucus layer and increases intestinal inflammation. The use of antioxidants and anti-inflammatory agents derived from natural sources has been recently highlighted as a new approach for the treatment of colitis. Oxyresveratrol (OXY) is an antioxidant known to have various beneficial effects on human health, such as anti-inflammatory, antibacterial activity, and antiviral activity. The aim of this study was to investigate the therapeutic effect of OXY in rats with dextran sulfate sodium (DSS)-induced acute colitis. OXY ameliorated DSS-induced colitis and repaired damaged intestinal mucosa. OXY downregulated the expression of pro-inflammatory cytokine genes (TNF-α, IL-6, and IL-1β) and chemokine gene MCP-1, while promoting the production of anti-inflammatory cytokine IL-10. OXY treatment also suppressed inflammation via inhibiting cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression in the colon, as well as the activity of myeloperoxidase (MPO). OXY exhibited anti-apoptotic effects, shifting the Bax/Bcl-2 balance. In conclusion, OXY might improve DSS-induced colitis by restoring the intestinal mucus layer and reducing inflammation within the intestine.

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Anti-Inflammatory Effect of Phytoncide in an Animal Model of Gastrointestinal Inflammation

Molecules ◽

10.3390/molecules26071895 ◽

2021 ◽

Vol 26 (7) ◽

pp. 1895

Author(s):

Azra Memon ◽

Bae Yong Kim ◽

Se-eun Kim ◽

Yuliya Pyao ◽

Yeong-Geun Lee ◽

...

Keyword(s):

Nitric Oxide ◽

Animal Model ◽

Gastric Ulcer ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Inos Expression ◽

Gastrointestinal Inflammation ◽

Anti Inflammatory ◽

Oxide Synthase ◽

Inflammatory Effect

Background: Phytoncide is known to have antimicrobial and anti-inflammatory properties. Purpose: This study was carried out to confirm the anti-inflammatory activity of two types of phytoncide extracts from pinecone waste. Methods: We made two types of animal models to evaluate the efficacy, an indomethacin-induced gastroenteritis rat model and a dextran sulfate sodium-induced colitis mouse model. Result: In the gastroenteritis experiment, the expression of induced-nitric oxide synthase (iNOS), a marker for inflammation, decreased in the phytoncide-supplemented groups, and gastric ulcer development was significantly inhibited (p < 0.05). In the colitis experiment, the shortening of the colon length and the iNOS expression were significantly suppressed in the phytoncide-supplemented group (p < 0.05). Conclusions: Through this study, we confirmed that phytoncide can directly inhibit inflammation in digestive organs. Although further research is needed, we conclude that phytoncide has potential anti-inflammatory properties in the digestive tract and can be developed as a functional agent.

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Inflammatory responses of C57BL/6NKorl mice to dextran sulfate sodium-induced colitis: comparison between three C57BL/6 N sub-strains

Laboratory Animal Research ◽

10.1186/s42826-021-00084-2 ◽

2021 ◽

Vol 37 (1) ◽

Author(s):

Sou Hyun Kim ◽

Doyoung Kwon ◽

Seung Won Son ◽

Tae Bin Jeong ◽

Seunghyun Lee ◽

...

Keyword(s):

Animal Model ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Inflammatory Responses ◽

Inbred Mouse ◽

Clinical Signs ◽

Safety Evaluation ◽

Inbred Mouse Strain ◽

Drug Safety Evaluation ◽

Factor Α

Abstract Background Inflammatory bowel disease (IBD), including both Crohn’s disease and ulcerative colitis, are chronic human diseases that are challenging to cure and are often unable to be resolved. The inbred mouse strain C57BL/6 N has been used in investigations of IBD as an experimental animal model. The purpose of the current study was to compare the inflammatory responsiveness of C57BL/6NKorl mice, a sub-strain recently established by the National Institute of Food and Drug Safety Evaluation (NIFDS), with those of C57BL/6 N mice from two different sources using a dextran sulfate sodium (DSS)-induced colitis model. Results Male mice (8 weeks old) were administered DSS (0, 1, 2, or 3%) in drinking water for 7 days. DSS significantly decreased body weight and colon length and increased the colon weight-to-length ratio. Moreover, severe colitis-related clinical signs including diarrhea and rectal bleeding were observed beginning on day 4 in mice administered DSS at a concentration of 3%. DSS led to edema, epithelial layer disruption, inflammatory cell infiltration, and cytokine induction (tumor necrosis factor-α, interleukin-6, and interleukin-1β) in the colon tissues. However, no significant differences in DSS-promoted abnormal symptoms or their severity were found between the three sub-strains. Conclusions These results indicate that C57BL/6NKorl mice responded to DSS-induced colitis similar to the generally used C57BL6/N mice, thus this newly developed mouse sub-strain provides a useful animal model of IBD.

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