Downregulation of CYP3A and P-Glycoprotein in the Secondary Inflammatory Response of Mice With Dextran Sulfate Sodium–Induced Colitis and Its Contribution to Cyclosporine A Blood Concentrations

Lachnum polysaccharide alleviated dextran sulfate sodium induced experimental colitis through inhibiting excessive inflammatory response, inflammasome activation, endoplasmic reticulum stress and oxidative/nitrosative stress.

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Changes in the Pharmacokinetics of Phenytoin in Dextran Sulfate Sodium–Induced Ulcerative Colitis in Mice

International Journal of Toxicology ◽

10.1177/1091581817735987 ◽

2017 ◽

Vol 36 (6) ◽

pp. 485-491 ◽

Cited By ~ 1

Author(s):

Yoshiki Kusunoki ◽

Yurika Kido ◽

Yuichi Naito ◽

Risako Kon ◽

Nanaho Mizukami ◽

...

Keyword(s):

Ulcerative Colitis ◽

Protein Expression ◽

Messenger Rna ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Plasma Concentrations ◽

Control Group ◽

Time Curve ◽

Blood Concentrations ◽

Expression Levels

We previously demonstrated that the expression levels of drug-metabolizing enzymes, cytochrome P450 (CYP) enzymes, in the liver are significantly decreased in a murine model of ulcerative colitis (UC). In this study, we investigated changes in the pharmacokinetics of phenytoin, a CYP2C substrate drug, in the presence of UC. Colitis was induced by feeding male mice 3.5% dextran sulfate sodium (DSS) dissolved in drinking water for 10 days. The messenger RNA (mRNA) expression of CYP2C29 and CYP2C37 and the protein expression of CYP2C in the liver were evaluated via real-time reverse transcription–polymerase chain reaction and Western blotting, respectively. In DSS-treated animals, both mRNA and protein expression levels of CYP2C in the liver were significantly reduced relative to those in control animals (by 20%-40%). Phenytoin (30 mg/kg) was administered orally in a single dose to mice, and plasma concentrations were measured. Plasma concentrations of phenytoin were higher in the DSS-treated group than in the control group at 12, 24, and 36 hours after administration. Animals given DSS also exhibited a higher area under the plasma concentration–time curve extrapolated to infinity (AUCinf, 315 μg·h/mL), a delayed elimination half-life ( T1/2, 8.1 hours), and a decreased body clearance (CL/F, 3.52 mL/h) compared with that of control animals (AUCinf, 215 μg·h/mL; T1/2, 3.6 h; CL/F, 5.58 mL/h). This study indicated that the presence of UC decreases CYP2C expression levels in the liver, thereby delaying the metabolism of CYP2C substrates, including phenytoin, and increasing blood concentrations of these substrates.

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T Cell-Specific Knockout of STAT3 Ameliorates Dextran Sulfate Sodium-Induced Colitis by Reducing the Inflammatory Response

Immune Network ◽

10.4110/in.2018.18.e30 ◽

2018 ◽

Vol 18 (4) ◽

Cited By ~ 3

Author(s):

Sun-Ho Kwon ◽

Eun-Bi Seo ◽

Song-Hee Lee ◽

Chung-Hyun Cho ◽

Sung Joon Kim ◽

...

Keyword(s):

T Cell ◽

Inflammatory Response ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium

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Upregulation of P-glycoprotein by probiotics in intestinal epithelial cells and in the dextran sulfate sodium model of colitis in mice

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00027.2011 ◽

2011 ◽

Vol 300 (6) ◽

pp. G1115-G1123 ◽

Cited By ~ 28

Author(s):

Seema Saksena ◽

Sonia Goyal ◽

Geetu Raheja ◽

Varsha Singh ◽

Maria Akhtar ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Epithelial Cells ◽

Bowel Disease ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Intestinal Epithelial Cells ◽

Myeloperoxidase Activity ◽

Intestinal Epithelial ◽

P Glycoprotein ◽

Inflammatory Bowel

P-glycoprotein (P-gp) mediates efflux of xenobiotics and bacterial toxins from the intestinal mucosa into the lumen. Dysregulation of P-gp has been implicated in inflammatory bowel disease. Certain probiotics have been shown to be effective in treating inflammatory bowel disease. However, direct effects of probiotics on P-gp are not known. Current studies examined the effects of Lactobacilli on P-gp function and expression in intestinal epithelial cells. Caco-2 monolayers and a mouse model of dextran sulfate sodium-induced colitis were utilized. P-gp activity was measured as verapamil-sensitive [3H]digoxin transepithelial flux. Multidrug resistant 1 (MDR1)/P-gp expression was measured by real-time quantitative PCR and immunoblotting. Culture supernatant (CS; 1:10 or 1:50, 24 h) of Lactobacillus acidophilus or Lactobacillus rhamnosus treatment of differentiated Caco-2 monolayers (21 days postplating) increased (∼3-fold) MDR1/P-gp mRNA and protein levels. L. acidophilus or L. rhamnosus CS stimulated P-gp activity (∼2-fold, P < 0.05) via phosphoinositide 3-kinase and ERK1/2 MAPK pathways. In mice, L. acidophilus or L. rhamnosus treatment (3 × 109 colony-forming units) increased mdr1a/P-gp mRNA and protein expression in the ileum and colon (2- to 3-fold). In the dextran sulfate sodium (DSS)-induced colitis model (3% DSS in drinking water for 7 days), the degree of colitis as judged by histological damage and myeloperoxidase activity was reduced by L. acidophilus. L. acidophilus treatment to DSS-treated mice blocked the reduced expression of mdr1a/P-gp mRNA and protein in the distal colon. These findings suggest that Lactobacilli or their soluble factors stimulate P-gp expression and function under normal and inflammatory conditions. These data provide insights into a novel mechanism involving P-gp upregulation in beneficial effects of probiotics in intestinal inflammatory disorders.

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Dietary polysaccharide-rich extract from Eucheuma cottonii modulates the inflammatory response and suppresses colonic injury on dextran sulfate sodium-induced colitis in mice

PLoS ONE ◽

10.1371/journal.pone.0205252 ◽

2018 ◽

Vol 13 (10) ◽

pp. e0205252 ◽

Cited By ~ 13

Author(s):

Sabri Sudirman ◽

Yuan-Hua Hsu ◽

Jia-Ling He ◽

Zwe-Ling Kong

Keyword(s):

Inflammatory Response ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Colonic Injury ◽

Eucheuma Cottonii

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Prevention and Alleviation of Dextran Sulfate Sodium Salt-Induced Inflammatory Bowel Disease in Mice With Bacillus subtilis-Fermented Milk via Inhibition of the Inflammatory Responses and Regulation of the Intestinal Flora

Frontiers in Microbiology ◽

10.3389/fmicb.2020.622354 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xuan Zhang ◽

Yanjun Tong ◽

Xiaomei Lyu ◽

Jing Wang ◽

Yuxue Wang ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bacillus Subtilis ◽

Inflammatory Response ◽

Oral Administration ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Intestinal Flora ◽

Fermented Milk ◽

Mucosal Barrier ◽

Inflammatory Bowel

The pathogenesis of inflammatory bowel disease (IBD) might be related to the local inflammatory damage and the dysbacteriosis of intestinal flora. Probiotics can regulate the intestinal flora and ameliorate IBD. The probiotic Bacillus subtilis strain B. subtilis JNFE0126 was used as the starter of fermented milk. However, the therapeutic effects of B. subtilis-fermented milk on IBD remain to be explored. In this research, the therapeutic effect of B. subtilis-fermented milk on dextran sulfate sodium salt (DSS)-induced IBD mouse model was evaluated. Besides, the expression of pro-inflammatory/anti-inflammatory cytokines, the proliferation of the intestinal stem cells, and the reconstruction of the mucosa barrier were investigated. Finally, alteration of the gut microbiota was investigated by taxonomic analysis. As shown by the results, the disease activity index (DAI) of IBD was significantly decreased through oral administration of B. subtilis (JNFE0126)-fermented milk, and intestinal mucosa injury was attenuated. Moreover, B. subtilis could reduce the inflammatory response of the intestinal mucosa, induce proliferation of the intestinal stem cell, and promote reconstruction of the mucosal barrier. Furthermore, B. subtilis could rebalance the intestinal flora, increasing the abundance of Bacillus, Alistipes, and Lactobacillus while decreasing the abundance of Escherichia and Bacteroides. In conclusion, oral administration of the B. subtilis-fermented milk could alleviate DSS-induced IBD via inhibition of inflammatory response, promotion of the mucosal barrier reconstruction, and regulation of the intestinal flora.

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