scholarly journals Exposure to the Harmful Algal Bloom (HAB) Toxin Microcystin-LR (MC-LR) Prolongs and Increases Severity of Dextran Sulfate Sodium (DSS)-Induced Colitis

Toxins ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 371 ◽  
Author(s):  
Robin C. Su ◽  
Thomas M. Blomquist ◽  
Andrew L. Kleinhenz ◽  
Fatimah K. Khalaf ◽  
Prabhatchandra Dube ◽  
...  
Keyword(s):  
Weight Loss ◽  
Algal Blooms ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Harmful Algal Bloom ◽  
Tnf Α ◽  
Environmental Toxin ◽  
Genetic And Environmental Factors ◽  
The Impact ◽  
Bloody Stools

Inflammatory Bowel Disease (IBD) represents a collection of gastrointestinal disorders resulting from genetic and environmental factors. Microcystin-leucine arginine (MC-LR) is a toxin produced by cyanobacteria during algal blooms and demonstrates bioaccumulation in the intestinal tract following ingestion. Little is known about the impact of MC-LR ingestion in individuals with IBD. In this study, we sought to investigate MC-LR’s effects in a dextran sulfate sodium (DSS)-induced colitis model. Mice were separated into four groups: (a) water only (control), (b) DSS followed by water (DSS), (c) water followed by MC-LR (MC-LR), and (d) DSS followed by MC-LR (DSS + MC-LR). DSS resulted in weight loss, splenomegaly, and severe colitis marked by transmural acute inflammation, ulceration, shortened colon length, and bloody stools. DSS + MC-LR mice experienced prolonged weight loss and bloody stools, increased ulceration of colonic mucosa, and shorter colon length as compared with DSS mice. DSS + MC-LR also resulted in greater increases in pro-inflammatory transcripts within colonic tissue (TNF-α, IL-1β, CD40, MCP-1) and the pro-fibrotic marker, PAI-1, as compared to DSS-only ingestion. These findings demonstrate that MC-LR exposure not only prolongs, but also worsens the severity of pre-existing colitis, strengthening evidence of MC-LR as an under-recognized environmental toxin in vulnerable populations, such as those with IBD.

scholarly journals CD40 Receptor Knockout Protects against Microcystin-LR (MC-LR) Prolongation and Exacerbation of Dextran Sulfate Sodium (DSS)-Induced Colitis

Biomedicines ◽  
2020 ◽  
Vol 8 (6) ◽  
pp. 149
Author(s):  
Robin C. Su ◽  
Emily A. Warner ◽  
Joshua D. Breidenbach ◽  
Apurva Lad ◽  
Thomas M. Blomquist ◽  
...  
Keyword(s):  
Weight Loss ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Monocyte Chemoattractant Protein 1 ◽  
The World ◽  
Colonic Ulceration ◽  
Bloody Stools ◽  
Pai 1

Inflammatory Bowel Disease (IBD) is one of the most common gastrointestinal (GI) disorders around the world, and includes diagnoses such as Crohn’s disease and ulcerative colitis. The etiology of IBD is influenced by genetic and environmental factors. One environmental perturbagen that is not well studied within the intestines is microcystin-leucine arginine (MC-LR), which is a toxin produced by cyanobacteria in freshwater environments around the world. We recently reported that MC-LR has limited effects within the intestines of healthy mice, yet interestingly has significant toxicity within the intestines of mice with pre-existing colitis induced by dextran sulfate sodium (DSS). MC-LR was found to prolong DSS-induced weight loss, prolong DSS-induced bloody stools, exacerbate DSS-induced colonic shortening, exacerbate DSS-induced colonic ulceration, and exacerbate DSS-induced inflammatory cytokine upregulation. In addition, we previously reported a significant increase in expression of the pro-inflammatory receptor CD40 in the colons of these mice, along with downstream products of CD40 activation, including plasminogen activator inhibitor-1 (PAI-1) and monocyte chemoattractant protein-1 (MCP-1). In the current study, we demonstrate that knocking out CD40 attenuates the effects of MC-LR in mice with pre-existing colitis by decreasing the severity of weight loss, allowing a full recovery in bloody stools, preventing the exacerbation of colonic shortening, preventing the exacerbation of colonic ulceration, and preventing the upregulation of the pro-inflammatory and pro-fibrotic cytokines IL-1β, MCP-1, and PAI-1. We also demonstrate the promising efficacy of a CD40 receptor blocking peptide to ameliorate the effects of MC-LR exposure in a proof-of-concept study. Our findings suggest for the first time that MC-LR acts through a CD40-dependent mechanism to exacerbate colitis.

Oat β-glucan ameliorates dextran sulfate sodium (DSS)-induced ulcerative colitis in mice

2015 ◽  
Vol 6 (11) ◽  
pp. 3454-3463 ◽  
Author(s):  
Bo Liu ◽  
Qinlu Lin ◽  
Tao Yang ◽  
Linna Zeng ◽  
Limin Shi ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Oral Administration ◽  
Inflammatory Cytokines ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Tnf Α

Oral administration of oat β-glucan ameliorates DSS induced colitis in mice by decreasing the expression of inflammatory cytokines TNF-α, IL-1β, IL-6 and iNOS.

The role of the complement and contact systems in the dextran sulfate sodium-induced colitis model: the effect of C1 inhibitor in inflammatory bowel disease

2010 ◽  
Vol 298 (6) ◽  
pp. G878-G883 ◽  
Author(s):  
Fengxin Lu ◽  
Stacey M. Fernandes ◽  
Alvin E. Davis
Keyword(s):  
Inflammatory Bowel Disease ◽  
Weight Loss ◽  
Bowel Disease ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Activity Index ◽  
Complement C3 ◽  
C1 Inhibitor ◽  
Inflammatory Bowel

The complement and contact systems may be involved in the pathophysiological process of inflammatory bowel disease (IBD). C1 inhibitor (C1INH) is the most important inhibitor of both the complement and contact systems. We evaluated the role of these systems and the effect of both active and inactive forms of C1INH (iC1INH) in dextran sulfate sodium (DSS)-induced colitis mouse model. Three percent DSS was used in drinking water to induce colitis in complement C3-deficient (C3−/−) mice, bradykinin type 2 receptor deficient (Bk2R−/−) mice, and C57BL/6 mice. After ten days DSS exposure, C3−/− mice exhibited markedly less weight loss than wild-type (WT) mice (12 ± 3.3% vs. 30 ± 1.2%, P < 0.05) and developed a milder disease-activity index (DAI), histological score, colon shortening, and myeloperoxidase (MPO) elevation ( P < 0.05, respectively). The Bk2R−/− mice were not protected from the disease. Seven-day treatment with either native C1INH or iC1INH reduced the severity of the disease in WT mice, as indicated by decreased weight loss (15 ± 1.8%, 14 ± 2.1% vs. 30 ± 1.2%, P < 0.05, respectively), DAI, intestinal tissue damage, and MPO elevation compared with untreated WT DSS control mice ( P < 0.05, respectively). These findings suggest that complement plays a role in the development of DSS-induced colitis and that blockade of the complement system might be useful for the acute phase of IBD treatment. C1INH, however, leads to an amelioration of DSS-induced colitis via a mechanism that does not involve the inhibition of complement or contact system activation but does result in significant suppression of leukocyte infiltration.

Westernized high-fat diet accelerates weight loss in dextran sulfate sodium-induced colitis in mice, which is further aggravated by supplementation of heme

2013 ◽  
Vol 24 (6) ◽  
pp. 1159-1165 ◽  
Author(s):  
Elise M.J. van der Logt ◽  
Tjasso Blokzijl ◽  
Roelof van der Meer ◽  
Klaas Nico Faber ◽  
Gerard Dijkstra
Keyword(s):  
Weight Loss ◽  
High Fat Diet ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
High Fat

Xanthoangelol Isolated from Angelica keiskei Roots Prevents Dextran Sulfate Sodium-Treated Colitis in Mice

2020 ◽  
Vol 10 (5) ◽  
pp. 655-663
Author(s):  
Yoshiyuki Kimura ◽  
Kimye Baba
Keyword(s):  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Activity Index ◽  
Gastrointestinal Diseases ◽  
Gastric Ulcers ◽  
Eosinophil Infiltration ◽  
Full Blood Count ◽  
Therapeutic Effects ◽  
Tnf Α ◽  
Angelica Keiskei

Background: The therapeutic effects of a number of natural products on Inflammatory Bowel Disease (IBD) have recently been examined in detail. The whole herb and roots of Angelica keiskei (Umblliferae) have traditionally been used as a diuretic, to treat gastrointestinal diseases such as gastric ulcers and diarrhea in Japan. Objectives: The present study was performed to investigate the effects of xanthoangelol, a major chalcone of Angelica keiskei roots, on diarrhea and inflammation in the large intestine of IBD model mice. Methods: Xanthoangelol (10 & 25 mg/kg) was orally administered to mice with 3% Dextran Sulfate Sodium (DSS)-induced colitis. Blood samples were collected during the experimental period, subjected to a full blood count test, and colonic cytokine and chemokine levels were measured. Results: Xanthoangelol (25 mg/kg) reduced the Disease Activity Index (DAI) of colitis. It also attenuated DSS-induced reductions in red blood cell and platelet counts as well as Hb and Ht levels. A histological examination of the colon using direct fast scarlet staining showed that xanthoangelol prevented DSS-induced mucosal ulceration and eosinophil infiltration. Xanthoangelol also reduced DSS-induced increases in colonic MCP-1, IL-1β, and TNF-α levels. Conclusions: Xanthoangelol reduced DSS-induced increases in colonic IL-1β, TNF-α, and MCP-1 levels and prevented eosinophil infiltration, which supports its potential as a treatment for IBD.

scholarly journals Suppression of Th17 Cell Response in the Alleviation of Dextran Sulfate Sodium-Induced Colitis by Ganoderma lucidum Polysaccharides

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Bing Wei ◽  
Ran Zhang ◽  
Jingbo Zhai ◽  
Junfeng Zhu ◽  
Fangli Yang ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Ganoderma Lucidum ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Therapeutic Potential ◽  
Activity Index ◽  
Survival Rates ◽  
Body Weight Loss ◽  
Disease Activity Index

Background. Ganoderma lucidum polysaccharides (GLP) has anti-inflammatory and immunomodulatory effects. Dysregulated immune responses are involved in the pathogenesis of dextran sulfate sodium (DSS)-induced colitis. The aim of this study was to assess the therapeutic potential of GLP to alleviate DSS-induced colitis. Methods. The mice were administered with GLP by intragastric gavage daily for two weeks prior to the DSS treatment. Mice were orally administered with 2.5% DSS dissolved in drinking water with GLP or water treatment for 6 days. The mice were killed on day 7 after induction of colitis. Survival rates, body weight loss, colon lengths, histological changes, and disease activity index scores (DAI) were evaluated. Results. GLP significantly improved survival rates, colon length shortening, body weight loss, histopathological score, and DAI scores in mice with DSS-induced colitis. GLP markedly suppressed the secretions of TNF-α, IL-1β, IL-6, IL-17A, and IL-4 and significantly affected populations of Th17 cells, B cells, NK cells, and NKT cells in the lamina propria lymphocytes. Conclusions. GLP prevented inflammation, maintained intestinal homeostasis, and regulated the intestinal immunological barrier functions in mice with DSS-induced colitis.

scholarly journals Mitigation of Colonic Inflammation in Dextran Sulfate Sodium-treated Mice by Dietary Supplementation with Soybean Fiber (P06-079-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Joshua Lambert ◽  
Vijaya Indukuri ◽  
Weslie Khoo ◽  
Jose Urena ◽  
Benjamin Chrisfield
Keyword(s):  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Dietary Supplementation ◽  
Pcr Analysis ◽  
Spleen Weight ◽  
Protective Effects ◽  
Colonic Inflammation ◽  
Markers Of Inflammation ◽  
Gut Barrier Function ◽  
The Impact

Abstract Objectives Soybean fiber (SBF) is an insoluble, but highly fermentable dietary fiber. Previous in vitro fermentation studies with human feces have shown that SBF produces 1.5–8 times more acetate, propionate, and butyrate than oat bran, corn bran, or wheat bran fiber. Short chain fatty acids (SCFA) have been reported to play a key role in maintaining colon health and reducing inflammation. The impact of dietary SBF on colonic inflammation has not previously been examined. Our objective was to determine the anti-inflammatory efficacy of dietary supplementation with SBF in a mouse model of acute colonic inflammation. Methods Male C57BL/6 J mice (5 weeks old) were randomized to AIN93G diet (CTL) or diet where 40% of the fiber was replaced with SBF (SBF-Hi). After 2 weeks of pretreatment, mice were given 2% dextran sulfate sodium (DSS) as the sole source of drinking fluid for 1 week to induce colonic inflammation. During DSS treatment, mice were maintained on their diet treatments. After DSS treatment, mice were euthanized and colonic inflammation was assessed. Results DSS-treated mice had significantly larger spleens and shorter colons than mice treated with water. SBF-Hi mitigated DSS-induced increases in spleen weight (20% lower) and colon shortening (15% longer). Quantitative, reverse transcriptase PCR analysis showed that DSS-treatment increased colonic mRNA expression of interleukin-6 (Il6) and tumor necrosis factor-a (Tnfa) by 3-fold compared to water-treated mice. Dietary supplementation with SBF blunted these increases in Il6 and Tnfa by 87% and 71%, respectively. Conclusions Our results suggest that dietary supplementation with SBF may be a useful approach to mitigate colonic inflammation. On-going studies are focused on determining fecal levels of SCFA and measuring protein markers of inflammation and gut barrier function. Future studies are needed to evaluate whether the protective effects observed in this study are maintained in situations of more chronic colonic inflammation. Funding Sources This work was funded by a grant from the Pennsylvania Soybean Board and by USDA National Institute of Food and Agriculture Appropriations under Project PEN04565.

scholarly journals TSG-6 in extracellular vesicles from canine mesenchymal stem/stromal is a major factor in relieving DSS-induced colitis

2019 ◽  
Author(s):  
Ju-Hyun An ◽  
Woo-Jin Song ◽  
Qiang Li ◽  
Min-Ok Ryu ◽  
A-Ryung Nam ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Qrt Pcr ◽  
Tnf Α ◽  
Key Factor ◽  
Ifn Γ ◽  
Underlying Mechanisms ◽  
Factor Α ◽  
Necrosis Factor

AbstractMesenchymal stem/stromal cell (MSC)-derived extracellular vesicles (EV) have been reported to be beneficial against dextran sulfate sodium (DSS)-induced colitis in mice. However, the underlying mechanisms have not been fully elucidated. We hypothesize that the tumor necrosis factor-α-stimulated gene/protein 6 (TSG-6) in EVs is a key factor influencing the alleviation of colitis symptoms. DSS-induced colitis mice (C57BL/6, male, n = 6-8/group) were intraperitoneally administered EVs (100 ug/mice) on day 1, 3, and 5; colon tissues were collected on day 10 for histopathological, qRT-PCR, western blot, and immunofluorescence analyses. In mice injected with EV, inflammation was alleviated. Indeed, EVs regulated the levels of pro- and anti-inflammatory cytokines, such as TNF-α, IL-1β, IFN-γ, IL-6, and IL-10 in inflamed colons. However, when injected with TSG-6 depleted EV, the degree of inflammatory relief was reduced. Furthermore, TSG-6 in EVs plays a key role in increasing regulatory T cells (Tregs) in the colon. In conclusion, this study shows that TSG-6 in EVs is a major factor in the relief of DSS-induced colitis, by increasing the number of Tregs in the colon.

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