Weight loss is a sufficient and economical single outcome measure of murine dextran sulfate sodium colitis

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.

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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

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00400.2009 ◽

2010 ◽

Vol 298 (6) ◽

pp. G878-G883 ◽

Cited By ~ 22

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.

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

The Journal of Nutritional Biochemistry ◽

10.1016/j.jnutbio.2012.09.001 ◽

2013 ◽

Vol 24 (6) ◽

pp. 1159-1165 ◽

Cited By ~ 23

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

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

Journal of Immunology Research ◽

10.1155/2018/2906494 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 3

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.

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

Biomedicines ◽

10.3390/biomedicines8060149 ◽

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.

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Pretreatment and Treatment WithL-Arginine Attenuate Weight Loss and Bacterial Translocation in Dextran Sulfate Sodium Colitis

Journal of Parenteral and Enteral Nutrition ◽

10.1177/0148607115581374 ◽

2016 ◽

Vol 40 (8) ◽

pp. 1131-1139 ◽

Cited By ~ 13

Author(s):

Maria Emília Rabelo Andrade ◽

Rosana das Graças Carvalho dos Santos ◽

Anne Danieli Nascimento Soares ◽

Kátia Anunciação Costa ◽

Simone Odília Antunes Fernandes ◽

...

Keyword(s):

Weight Loss ◽

Bacterial Translocation ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium

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Oldenlandia diffusa Ameliorates Dextran Sulphate Sodium-Induced Colitis Through Inhibition of NF-κB Activation

The American Journal of Chinese Medicine ◽

10.1142/s0192415x11009330 ◽

2011 ◽

Vol 39 (05) ◽

pp. 957-969 ◽

Cited By ~ 8

Author(s):

Su-Jin Kim ◽

Yang-Gui Kim ◽

Dae-Seung Kim ◽

Yong-Deok Jeon ◽

Min-Cheol Kim ◽

...

Keyword(s):

Weight Loss ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Intestinal Inflammation ◽

Clinical Signs ◽

Gastrointestinal Disorder ◽

Nuclear Factor Κb ◽

Activation Of Transcription ◽

Inflammatory Bowel ◽

Oldenlandia Diffusa

Ulcerative colitis (UC) is an inflammatory bowel disease, which is a chronic gastrointestinal disorder. Oldenlandia diffusa (OD) has been used as a traditional oriental medicine for inflammation. However, the regulatory effect and molecular mechanism of OD in intestinal inflammation are not yet understood. This study investigated the protective effect of OD in dextran sulfate sodium (DSS)-induced colitis. Mice treated with DSS showed remarkable clinical signs, including weight loss, and reduced colon length. Administration of OD attenuated these signs and significantly suppressed levels of interleukin (IL)-6, IL-1β and expression of cyclooxygenase-2 in DSS-treated colon tissues. OD also reduced the activation of transcription nuclear factor-κB p65 in DSS-treated colon tissues. Hentriacontane, a constituent of OD, attenuated weight loss, colon shortening, and levels of IL-6 caused by DSS. Taken together, the results provide experimental evidence that OD might be a useful therapeutic medicine for patients with UC.

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