scholarly journals Rosa canina L. Can Restore Endoplasmic Reticulum Alterations, Protein Trafficking and Membrane Integrity in a Dextran Sulfate Sodium-Induced Inflammatory Bowel Disease Phenotype

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 441
Author(s):  
Dalanda Wanes ◽  
Mohamad Toutounji ◽  
Hichem Sebai ◽  
Sandra Rizk ◽  
Hassan Y. Naim
Keyword(s):  
Inflammatory Bowel Disease ◽  
Endoplasmic Reticulum ◽  
Lipid Rafts ◽  
Protein Trafficking ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Membrane Integrity ◽  
Membrane Glycoproteins ◽  
Rosa Canina ◽  
Inflammatory Bowel

Rosa canina L. is a natural polyphenol-rich medicinal plant that exhibits antioxidant and anti-inflammatory activities. Recent in vivo studies have demonstrated that a methanol extract of Rosa canina L. (RCME) has reversed an inflammatory bowel disease (IBD)-like phenotype that has been triggered by dextran sulfate sodium (DSS) in mice. In the current study, we investigated the effects of RCME on perturbations of cellular mechanisms induced by DSS-treatment of intestinal Caco-2 cells, including stress response in the endoplasmic reticulum (ER), protein trafficking and sorting as well as lipid rafts integrity and functional capacities of an intestinal enzyme. 6 days post-confluent cells were treated for 24 h with DSS (3%) or simultaneously with DSS (3%) and RCME (100 µg/mL) or exclusively with RCME (100 µg/mL) or not treated. The results obtained demonstrate the ability of RCME to counteract the substantial increase in the expression levels of several ER stress markers in DSS-treated cells. Concomitantly, the delayed trafficking of intestinal membrane glycoproteins sucrase-isomaltase (SI) and dipeptidyl peptidase 4 (DPP4) induced by DSS between the ER and the Golgi has been compromised by RCME. Furthermore, RCME restored the partially impaired polarized sorting of SI and DPP4 to the brush border membrane. An efficient sorting mechanism of SI and DPP4 is tightly associated with intact lipid rafts structures in the trans-Golgi network (TGN), which have been distorted by DSS and normalized by RCME. Finally, the enzymatic activities of SI are enhanced in the presence of RCME. Altogether, DSS treatment has triggered ER stress, impaired trafficking and function of membrane glycoproteins and distorted lipid rafts, all of which can be compromised by RCME. These findings indicate that the antioxidants in RCME act at two major sites in Caco-2 cells, the ER and the TGN and are thus capable of maintaining the membrane integrity by correcting the sorting of membrane-associated proteins.

Sucralose enhances the susceptibility of dextran sulfate sodium (DSS) induced colitis in mice with changes in gut microbiota

2021 ◽  
Author(s):  
Mengru Guo ◽  
Xinran Liu ◽  
Yiwei Tan ◽  
Fangyuan Kang ◽  
Xinghua Zhu ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Gut Microbiota ◽  
Bowel Disease ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Artificial Sweeteners ◽  
Epidemiological Changes ◽  
Inflammatory Bowel

Sucralose is one of the most widely used artificial sweeteners, free of nutrients and calories. It’s approval and uses correlate many of the worldwide epidemiological changes of inflammatory bowel disease...

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.

scholarly journals Dextran sulfate sodium mouse model of inflammatory bowel disease evaluated for systemic genotoxicity via blood micronucleus and Pig-a gene mutation assays

Mutagenesis ◽  
2020 ◽  
Vol 35 (2) ◽  
pp. 161-167
Author(s):  
Christopher Kirby ◽  
Ayesha Baig ◽  
Svetlana L Avlasevich ◽  
Dorothea K Torous ◽  
Shuchang Tian ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Mouse Model ◽  
Bowel Disease ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
High Dose ◽  
Significant Treatment ◽  
Blood Samples ◽  
Inflammatory Bowel ◽  
Blood Specimens

Abstract Inflammatory bowel disease (IBD) is an important risk factor for gastrointestinal cancers. Inflammation and other carcinogenesis-related effects at distal, tissue-specific sites require further study. In order to better understand if systemic genotoxicity is associated with IBD, we exposed mice to dextran sulfate sodium salt (DSS) and measured the incidence of micronucleated cells (MN) and Pig-a mutant phenotype cells in blood erythrocyte populations. In one study, 8-week-old male CD-1 mice were exposed to 0, 1, 2, 3 or 4% w/v DSS in drinking water. The 4-week in-life period was divided into four 1-week intervals—alternately on then off DSS treatment. Low volume blood samples were collected for MN analysis at the end of each week, and cardiac blood samples were collected at the end of the 4-week period for Pig-a analyses. The two highest doses of DSS were observed to induce significant increases in reticulocyte frequencies. Even so, no statistically significant treatment-related effects on the genotoxicity biomarkers were evident. While one high-dose mouse showed modestly elevated MN frequencies during the DSS treatment cycles, it also exhibited exceptionally high reticulocyte frequencies (e.g. 18.7% at the end of the second DSS cycle). In a second study, mice were treated with 0 or 4% DSS for 9–18 consecutive days. Exposure was continued until rectal bleeding or morbidity was evident, at which point the treatment was terminated and blood was collected for MN analysis. The Pig-a assay was conducted on samples collected 29 days after the start of treatment. The initial blood specimens showed highly elevated reticulocyte frequencies in DSS-exposed mice (mean ± SEM = 1.75 ± 0.10% vs. 13.04 ± 3.66% for 0 vs. 4% mice, respectively). Statistical analyses showed no treatment-related effect on MN or Pig-a mutant frequencies. Even so, the incidence of MN versus reticulocytes in the DSS-exposed mice were positively correlated (linear fit R2 = 0.657, P = 0.0044). Collectively, these results suggest that in the case of the DSS CD-1 mouse model, systemic effects include stress erythropoiesis but not remarkable genotoxicity. To the extent MN may have been slightly elevated in a minority of individual mice, these effects appear to be secondary, likely attributable to stimulated erythropoiesis.

scholarly journals 89Zr-pro-MMP-9 F(ab′)2 detects colitis induced intestinal and kidney fibrosis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Nicole Dmochowska ◽  
William Tieu ◽  
Marianne D. Keller ◽  
Courtney A. Hollis ◽  
Melissa A. Campaniello ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Ex Vivo ◽  
Antibody Fragments ◽  
Matrix Metalloproteases ◽  
Common Complication ◽  
Kidney Fibrosis ◽  
Intestinal Fibrosis ◽  
Inflammatory Bowel

AbstractIntestinal fibrosis is a common complication of inflammatory bowel disease but remains difficult to detect. Matrix metalloproteases (MMPs) have key roles in fibrosis and are therefore potential targets for fibrosis detection. We determined whether immunoPET of F(ab′)2 antibody fragments targeting MMPs detects colitis induced colonic fibrosis. Mice were administered 2% dextran sulfate sodium treated water for 1 cycle (inflamed) or 3 cycles (fibrotic), or were untreated (control). Colonic and kidney collagen, innate cytokine, MMPs and fecal MPO concentrations were analyzed by multiplex/ELISA. α-pro-MMP-9 F(ab′)2 fragments were engineered and conjugated to 89Zr for PET imaging, ex-vivo Cherenkov analysis and bio-distribution. Colonic innate cytokine concentrations and fecal myeloperoxidase were increased in inflamed mice but not fibrotic mice, while collagen concentrations were increased in fibrotic mice. MMPs were increased in inflamed mice, but only pro-MMP-9 remained increased in fibrotic mice. 89Zr-pro-MMP-9 F(ab′)2 uptake was increased in the intestine but also in the kidney of fibrotic mice, where collagen and pro-MMP-9 concentrations were increased. 89Zr-pro-MMP-9 F(ab′)2 detects colitis induced intestinal fibrosis and associated kidney fibrosis.

scholarly journals The anti-inflammatory effect and potential mechanism of cardamonin in DSS-induced colitis

2015 ◽  
Vol 309 (7) ◽  
pp. G517-G527 ◽  
Author(s):  
Gaiyan Ren ◽  
Aning Sun ◽  
Chao Deng ◽  
Jingjing Zhang ◽  
Xiaojun Wu ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Protein Kinase ◽  
Bowel Disease ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Mitogen Activated Protein Kinase ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Mitogen Activated Protein ◽  
Inflammatory Bowel

Cardamonin is a naturally occurring chalcone with strong anti-inflammatory activity. However, the direct effect of cardamonin on intestinal inflammation remains elusive. In the present study, we found that cardamonin markedly ameliorated dextran sulfate sodium-induced mouse body weight loss, diarrhea, colon shortening, spleen swelling, and histological damage, which correlated with a decline in the activity of myeloperoxidase and the production of nitric oxide, tumor necrosis factor-α and interleukin-6 in the colon. The upregulation of toll-like receptor 4 after dextran sulfate sodium treatment was associated with an increase in the activation of myeloid differentiation factor 88, interleukin-1 receptor-associated kinase-1, nuclear factor-κB (NF-κB) p65, inhibitor κBα, and inhibitor κB kinase-α/β, as well as the mitogen-activated protein kinase molecules of extracellular signal-regulated kinase and c-Jun NH2-terminal kinase, and this upregulation was reversed by cardamonin administration. Moreover, cardamonin blocked the nuclear translocation of NF-κB p65, inhibited NF-κB-luciferase activity, and downregulated NF-κB target genes expression. The present study clearly demonstrates a beneficial effect of cardamonin on experimental inflammatory bowel disease via a mechanism associated with suppression of toll-like receptor 4 expression and inactivation of NF-κB and mitogen-activated protein kinase pathways. This study may give insight into the further evaluation of the therapeutic potential of cardamonin or its derivatives for human inflammatory bowel disease.

scholarly journals Metabolic profiling of liver in C57BL/6 mice with DSS-induced inflammatory bowel disease by untargeted metabolomics analysis

2019 ◽  
Author(s):  
Zhongquan Xin ◽  
Zhenya Zhai ◽  
Hongrong Long ◽  
Fan Zhang ◽  
Xiaojun Ni ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Metabolic Pathways ◽  
Dextran Sulfate ◽  
Acid Metabolism ◽  
Dextran Sulfate Sodium ◽  
Liver Disorder ◽  
Cecropin A ◽  
Inflammatory Bowel ◽  
Metabolomics Analysis

Abstract Background: Inflammatory bowel disease (IBD) is a systemic disease that frequently causes liver damage. However, the metabolic mechanism of liver disorder induced by IBD is still unclear. This study aimed to revile metabolic profiles of liver in mice which induced inflammatory bowel disease by dextran sulfate sodium (DSS) and treated by cecropin A and gentamicin . Methods: In this study, IBD mold mice were established, C57BL/6 mice were given water containing 2.5% dextran sulfate sodium (DSS) for 5 days. Subsequently, the mice were treated via intraperitoneally injected with saline, 15 mg/kg cecropin A, 5 mg/kg gentamicin for 3 days, respectively. The liver in IBD mold mice or treated by cecropin A and gentamicin, were performed metabolomics analysis through UPLC–Orbitrap–MS/MS. Database integration analysis software was used to identify metabolites of liver. Multivariate analysis, including principal component analysis (PCA), hierarchical cluster analysis (HCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA). Furthermore, metabolic pathway analysis was performed using MetaboAnalyst 4.0. Results: A total of 133 metabolites were identified in liver of mice and 20 key metabolites were considered as potential biomarkers were identified between the control and IBD group. There are 4 key metabolic pathways include bile acid metabolism, arachidonic acid metabolism, amino acid and protein metabolism, and steroid hormone biosynthesis in liver was disturbed by IBD, and we also found that those pathways were reversed when mice were treated by cecropin A and gentamicin. Conclusion: The results indicated that those differential metabolites and metabolic pathways changed in liver were likely to be caused by IBD. The further study shall be carried out to explore the mechanism of liver disorder induced by IBD.

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