In vivo Evaluation of Inflammatory Bowel Disease with the Aid of μPET and the Translocator Protein 18 kDa Radioligand [18F]DPA-714

Selenium (Se) as an essential micronutrient that has implications in human diseases, including inflammatory bowel disease (IBD), especially with respect to Se deficiencies. Recently, selenium nanoparticles (SeNPs) have attracted significant...

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Coated chitosan pellets containing rutin intended for the treatment of inflammatory bowel disease: In vitro characteristics and in vivo evaluation

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2011.10.045 ◽

2012 ◽

Vol 422 (1-2) ◽

pp. 151-159 ◽

Cited By ~ 26

Author(s):

Miloslava Rabišková ◽

Tereza Bautzová ◽

Jan Gajdziok ◽

Kateřina Dvořáčková ◽

Alf Lamprecht ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

In Vivo Evaluation ◽

Inflammatory Bowel

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Development and in vivo evaluation of chitosan beads for the colonic delivery of azathioprine for treatment of inflammatory bowel disease

European Journal of Pharmaceutical Sciences ◽

10.1016/j.ejps.2017.08.025 ◽

2017 ◽

Vol 109 ◽

pp. 269-279 ◽

Cited By ~ 8

Author(s):

Abdelrahman M. Helmy ◽

Mahmoud Elsabahy ◽

Ghareb M. Soliman ◽

Mahmoud A. Mahmoud ◽

Elsayed A. Ibrahim

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Colonic Delivery ◽

In Vivo Evaluation ◽

Chitosan Beads ◽

Inflammatory Bowel

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Fabrication, characterization and in vivo evaluation of luteolin loaded microspheres for inflammatory bowel disease

Advance Pharmaceutical Journal ◽

10.31024/apj.2020.5.3.4 ◽

2020 ◽

Vol 5 (3) ◽

pp. 103-112

Author(s):

Anil Kumar Pandey ◽

Alok Pal Jain ◽

Anjana Bhardwaj

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

In Vivo Evaluation ◽

Inflammatory Bowel

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The food additive EDTA aggravates colitis and colon carcinogenesis in mouse models

Scientific Reports ◽

10.1038/s41598-021-84571-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Rayko Evstatiev ◽

Adam Cervenka ◽

Tina Austerlitz ◽

Gunther Deim ◽

Maximilian Baumgartner ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Mouse Models ◽

Bowel Disease ◽

Intestinal Inflammation ◽

Food Additives ◽

Colorectal Carcinogenesis ◽

Testing Procedures ◽

Inflammatory Models ◽

Inflammatory Bowel

AbstractInflammatory bowel disease is a group of conditions with rising incidence caused by genetic and environmental factors including diet. The chelator ethylenediaminetetraacetate (EDTA) is widely used by the food and pharmaceutical industry among numerous other applications, leading to a considerable environmental exposure. Numerous safety studies in healthy animals have revealed no relevant toxicity by EDTA. Here we show that, in the presence of intestinal inflammation, EDTA is surprisingly capable of massively exacerbating inflammation and even inducing colorectal carcinogenesis at doses that are presumed to be safe. This toxicity is evident in two biologically different mouse models of inflammatory bowel disease, the AOM/DSS and the IL10−/− model. The mechanism of this effect may be attributed to disruption of intercellular contacts as demonstrated by in vivo confocal endomicroscopy, electron microscopy and cell culture studies. Our findings add EDTA to the list of food additives that might be detrimental in the presence of intestinal inflammation, but the toxicity of which may have been missed by regulatory safety testing procedures that utilize only healthy models. We conclude that the current use of EDTA especially in food and pharmaceuticals should be reconsidered. Moreover, we suggest that intestinal inflammatory models should be implemented in the testing of food additives to account for the exposure of this primary organ to environmental and dietary stress.

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An objective in vivo diagnostic method for inflammatory bowel disease

Royal Society Open Science ◽

10.1098/rsos.180107 ◽

2018 ◽

Vol 5 (3) ◽

pp. 180107 ◽

Cited By ~ 4

Author(s):

Sophie C. Payne ◽

Robert K. Shepherd ◽

Alicia Sedo ◽

James B. Fallon ◽

John B. Furness

Keyword(s):

Inflammatory Bowel Disease ◽

Real Time ◽

Bowel Disease ◽

Experimental Models ◽

Mucosal Barrier ◽

Trinitrobenzene Sulfonic Acid ◽

Inflammatory Damage ◽

Mucosal Barrier Function ◽

Inflammatory Bowel

Inflammatory damage to the bowel, as occurs in inflammatory bowel disease (IBD), is debilitating to patients. In both patients and animal experimental models, histological analyses of biopsies and endoscopic examinations are used to evaluate the disease state. However, such measurements often have delays and are invasive, while endoscopy is not quantitatively objective. Therefore, a real-time quantitative method to assess compromised mucosal barrier function is advantageous. We investigated the correlation of in vivo changes in electrical transmural impedance with histological measures of inflammation. Four platinum (Pt) ball electrodes were placed in the lumen of the rat small intestine, with a return electrode under the skin. Electrodes placed within the non-inflamed intestine generated stable impedances during the 3 h testing period. Following an intraluminal injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS), an established animal model of IBD, impedances in the inflamed region significantly decreased relative to a region not exposed to TNBS ( p < 0.05). Changes in intestinal transmural impedance were correlated ( p < 0.05) with histologically assessed damage to the mucosa and increases in neutrophil, eosinophil and T-cell populations at 3 h compared with tissue from control regions. This quantitative, real-time assay may have application in the diagnosis and clinical management of IBD.

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Preclinical Study in Vivo for New Pharmacological Approaches in Inflammatory Bowel Disease: A Systematic Review of Chronic Model of TNBS-Induced Colitis

Journal of Clinical Medicine ◽

10.3390/jcm8101574 ◽

2019 ◽

Vol 8 (10) ◽

pp. 1574 ◽

Cited By ~ 4

Author(s):

Silva ◽

Pinto ◽

Mateus

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Histological Evaluation ◽

Therapeutic Drug ◽

Average Dose ◽

Preclinical Studies ◽

Trinitrobenzenesulfonic Acid ◽

Chronic Model ◽

Inflammatory Bowel

The preclinical studies in vivo provide means of characterizing physiologic interactions when our understanding of such processes is insufficient to allow replacement with in vitro systems and play a pivotal role in the development of a novel therapeutic drug cure. Chemically induced colitis models are relatively easy and rapid to develop. The 2,4,6-trinitrobenzenesulfonic acid (TNBS) colitis model is one of the main models in the experimental studies of inflammatory bowel disease (IBD) since inflammation induced by TNBS mimics several features of Crohn’s disease. This review aims to summarize the existing literature and discuss different protocols for the induction of chronic model of TNBS-induced colitis. We searched MEDLINE via Pubmed platform for studies published through December 2018, using MeSH terms (Crohn Disease.kw) OR (Inflammatory Bowel Diseases.kw) OR (Colitis, Ulcerative.kw) AND (trinitrobenzenesulfonic acid.kw) AND (disease models, animal.kw) AND (mice.all). The inclusion criteria were original articles, preclinical studies in vivo using mice, chronic model of colitis, and TNBS as the inducer of colitis and articles published in English. Chronic TNBS-induced colitis is made with multiple TNBS intrarectal administrations in an average dose of 1.2 mg using a volume lower than 150 μL in 50% ethanol. The strains mostly used are Balb/c and C57BL/6 with 5–6 weeks. To characterize the preclinical model the parameters more used include body weight, stool consistency and morbidity, inflammatory biomarkers like interferon (IFN)-γ, myeloperoxidase (MPO), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10, presence of ulcers, thickness or hyperemia in the colon, and histological evaluation of the inflammation. Experimental chronic colitis is induced by multiple rectal instillations of TNBS increasing doses in ethanol using Balb/c and C57BL/6 mice.

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Deficiency in the anti-apoptotic protein DJ-1 promotes intestinal epithelial cell apoptosis and aggravates inflammatory bowel disease via p53

Journal of Biological Chemistry ◽

10.1074/jbc.ra119.010143 ◽

2020 ◽

Vol 295 (13) ◽

pp. 4237-4251 ◽

Cited By ~ 1

Author(s):

Jie Zhang ◽

Min Xu ◽

Weihua Zhou ◽

Dejian Li ◽

Hong Zhang ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Epithelial Cell ◽

Bowel Disease ◽

Intestinal Epithelial Cell ◽

Intestinal Inflammation ◽

Intestinal Epithelial ◽

P53 Expression ◽

Inflammatory Bowel

Parkinson disease autosomal recessive, early onset 7 (PARK7 or DJ-1) is involved in multiple physiological processes and exerts anti-apoptotic effects on multiple cell types. Increased intestinal epithelial cell (IEC) apoptosis and excessive activation of the p53 signaling pathway is a hallmark of inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD). However, whether DJ-1 plays a role in colitis is unclear. To determine whether DJ-1 deficiency is involved in the p53 activation that results in IEC apoptosis in colitis, here we performed immunostaining, real-time PCR, and immunoblotting analyses to assess DJ-1 expression in human UC and CD samples. In the inflamed intestines of individuals with IBD, DJ-1 expression was decreased and negatively correlated with p53 expression. DJ-1 deficiency significantly aggravated colitis, evidenced by increased intestinal inflammation and exacerbated IEC apoptosis. Moreover, DJ-1 directly interacted with p53, and reduced DJ-1 levels increased p53 levels both in vivo and in vitro and were associated with decreased p53 degradation via the lysosomal pathway. We also induced experimental colitis with dextran sulfate sodium in mice and found that compared with DJ-1−/− mice, DJ-1−/−p53−/− mice have reduced apoptosis and inflammation and increased epithelial barrier integrity. Furthermore, pharmacological inhibition of p53 relieved inflammation in the DJ-1−/− mice. In conclusion, reduced DJ-1 expression promotes inflammation and IEC apoptosis via p53 in colitis, suggesting that the modulation of DJ-1 expression may be a potential therapeutic strategy for managing colitis.

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