scholarly journals Fecal Lipocalin-2 as a Sensitive and Noninvasive Biomarker in the TNBS Crohn’s Inflammatory Bowel Disease Model

2016 ◽  
Vol 44 (8) ◽  
pp. 1084-1094 ◽  
Author(s):  
Heidi Hsieh ◽  
Jeffrey Morin ◽  
Cyndi Filliettaz ◽  
Rao Varada ◽  
Shelby LaBarre ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Body Weight ◽  
Bowel Disease ◽  
Saline Water ◽  
Disease Model ◽  
Recovery Phase ◽  
Lipocalin 2 ◽  
Trinitrobenzenesulfonic Acid ◽  
Noninvasive Biomarker ◽  
Inflammatory Bowel

Colitis induced by 2,4,6-Trinitrobenzenesulfonic acid (TNBS) has been used as a model for Crohn’s disease (CD) of inflammatory bowel disease (IBD). Lipocalin-2 (Lcn-2) is an emerging and clinically relevant biomarker of IBD. We investigated the performance of serum and fecal Lcn-2 in the TNBS model of colitis. Female, 7-week-old, BALB/c mice were administered intrarectally phosphate-buffered saline/water or 30% ethanol (vehicle control groups) for 5 days or TNBS for 5 days followed by a 28-day recovery phase. Serum and fecal levels of Lcn-2 were quantified, and effects on body weight, clinical scores, colon weight and length, gross pathology, and histopathology were investigated. Increased serum Lcn-2 levels correlated only with marked to severe inflammation. A clear differentiation in Lcn-2 fecal levels between TNBS-treated and vehicle-treated control mice was most noticeable on days 2 and 3. There was a strong correlation between body weight change, histopathologic scores of inflammation, and/or fecal Lcn-2 levels on days 2 and 5. Both serum and fecal Lcn-2 levels declined over time as the colonic mucosa recovered. Fecal Lcn-2 was found to be a more sensitive biomarker (vs. serum Lcn-2) and was able to discriminate mild, moderate, and severe colonic inflammation.

scholarly journals Predicting disease course in ulcerative colitis using stool proteins identified through an aptamer-based screen

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sanam Soomro ◽  
Suresh Venkateswaran ◽  
Kamala Vanarsa ◽  
Marwa Kharboutli ◽  
Malavika Nidhi ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Fecal Calprotectin ◽  
Disease Monitoring ◽  
Disease Course ◽  
Lipocalin 2 ◽  
Time Points ◽  
Inflammatory Bowel ◽  
Stool Samples

AbstractIn the search for improved stool biomarkers for inflammatory bowel disease (IBD), an aptamer-based screen of 1129 stool proteins was conducted using stool samples from an IBD cohort. Here we report that of the 20 proteins subsequently validated by ELISA, stool Ferritin, Fibrinogen, Haptoglobin, Hemoglobin, Lipocalin-2, MMP-12, MMP-9, Myeloperoxidase, PGRP-S, Properdin, Resistin, Serpin A4, and TIMP-1 are significantly elevated in both ulcerative colitis (UC) and Crohn’s disease (CD) compared to controls. When tested in a longitudinal cohort of 50 UC patients at 4 time-points, fecal Fibrinogen, MMP-8, PGRP-S, and TIMP-2 show the strongest positive correlation with concurrent PUCAI and PGA scores and are superior to fecal calprotectin. Unlike fecal calprotectin, baseline stool Fibrinogen, MMP-12, PGRP-S, TIMP-1, and TIMP-2 can predict clinical remission at Week-4. Here we show that stool proteins identified using the comprehensive aptamer-based screen are superior to fecal calprotectin alone in disease monitoring and prediction in IBD.

Nonhypoalbuminemic Inflammatory Bowel Disease in Dogs as Disease Model

2021 ◽  
Author(s):  
Juan Hernandez ◽  
Elodie Rouillé ◽  
Florian Chocteau ◽  
Marie Allard ◽  
Karine Haurogné ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Immune Responses ◽  
Bowel Disease ◽  
Interindividual Variability ◽  
Expression Patterns ◽  
Disease Model ◽  
Protein Loss ◽  
Tissue Concentrations ◽  
Inflammatory Bowel ◽  
Antibody Levels

Abstract Background The incidence of inflammatory bowel disease (IBD) is increasing worldwide, emphasizing the need of relevant models, as dogs spontaneously affected by IBD may be, for better knowledge of the disease’s physiopathology. Methods We studied 22 client-owned dogs suffering from IBD without protein loss and 14 control dogs. Biopsies were obtained from the duodenum, ileum, and colon. Inflammatory grade was assessed by histopathology, immunohistochemistry, and chemokine analysis. The expression of Toll-like receptors (TLR) in mucosa was immunohistochemically evaluated. Antibody levels against bacterial ligands (lipopolysaccharide [LPS] and flagellin) were measured in sera using enzyme-linked immunoassay. Results Dogs with IBD showed low to severe clinical disease. Histopathologically, the gut of dogs with IBD did not exhibit significant alterations compared with controls except in the colon. The number of CD3+ T lymphocytes was decreased in the ileum and colon of dogs with IBD compared with controls, whereas the numbers of Foxp3+, CD20+, and CD204+ cells were similar in the 2 groups. Three chemokines, but no cytokines, were detected at the protein level in the mucosa, and the disease poorly affected their tissue concentrations. Dogs with IBD exhibited higher serum reactivity against LPS and flagellin than controls but similar immunoreactivity against the receptors TLR4 and TLR5. In addition, TLR2 and TLR9 showed similar expression patterns in both groups of dogs. Conclusions Our data described dysregulated immune responses in dogs affected by IBD without protein loss. Despite fairly homogeneous dog cohorts, we were still faced with interindividual variability, and new studies with larger cohorts are needed to validate the dog as a model.

scholarly journals Therapeutic Effects of Beclomethasone Dipropionate Enemas on Colon Damage of Inflammatory Bowel Disease Model Rats

1998 ◽  
Vol 118 (6) ◽  
pp. 216-225 ◽  
Author(s):  
Shuji SHIMADA ◽  
Takao AOYAMA ◽  
Fuminori SHIBUYA ◽  
Katsuyoshi NAKAJIMA ◽  
Hajime KOTAKI ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Beclomethasone Dipropionate ◽  
Disease Model ◽  
Therapeutic Effects ◽  
Inflammatory Bowel

HEALING THROUGH CYTOKINE REGULATION IN DNBS INDUCED INFLAMMATORY BOWEL DISEASE IN RATS BY HOLARRHENA ANTIDYSENTERICA

INDIAN DRUGS ◽  
2016 ◽  
Vol 53 (08) ◽  
pp. 57-64
Author(s):  
S. Johari ◽  
◽  
C. Joshi ◽  
T. Gandhi
Keyword(s):  
Gene Expression ◽  
Inflammatory Bowel Disease ◽  
Body Weight ◽  
Bowel Disease ◽  
Stool Consistency ◽  
Cytokine Gene ◽  
Group Iii ◽  
Group I ◽  
Holarrhena Antidysenterica ◽  
Inflammatory Bowel

The objective of the study was to ascertain antioxidant, anti-inflammatory and cytokine gene regulation activity of Holarrhena antidysenterica (HA) in dinitrobenzene sulfonic acid (DNBS) induced inflammatory bowel disease (IBD) in rats. Sprague Dawley rats were divided into 6 groups, Group I (normal), Group II (50% ethanol intracolonically on 11th day), Group III (Model). Group IV to VI were given standard drug 5-amino salicylic acid (5-ASA) (100mg/kg) and hydromethanolic extract of Holarrhena antidysenterica (MEHA) 450 mg/kg and MEHA 600 mg/kg respectively for 18 days once p.o. Colitis was induced with DNBS (180mg/kg in 50% ethanol) intracolonically in animals of Group III-VI on 11th day. Body weight, food & water intake and stool consistency of each group was noted. On 18th day, blood was collected for cortisol estimation. Colon length and weight was measured. Cytokine gene expression studies of colon in group I, II, III, IV and VI was done using Real Time RT-PCR. Colon histopathology, Disease Activity Index (DAI) and Colon Mucosal Disease index (CMDI) parameters were studied. Nitric oxide (NO), malondialdehyde (MDA), myeloperoxidase (MPO) and superoxide dismutase (SOD) were estimated in colon homogenate. DNBS model control showed significant reduction in body weight, water and food intake, SOD, colon length and significant increase in stool consistency, colon weight, MDA, MPO, NO, CMDI, DAI, cortisol, IL-4, IL-6, IL-12 and IFN-gamma cytokines gene expression. Pretreatment with 5-ASA (100mg/kg) and MEHA (450 and 600 mg/kg) significantly reversed the above. MEHA reduced severity of IBD induced by DNBS through its anti-inflammatory, antioxidant and gene modulatory activity.

scholarly journals Lipocalin 2 links inflammation and ankylosis in the clinical overlap of inflammatory bowel disease (IBD) and ankylosing spondylitis (AS)

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Aifeng Lin ◽  
Robert D. Inman ◽  
Catherine J. Streutker ◽  
Zhenbo Zhang ◽  
Kenneth P. H. Pritzker ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Ankylosing Spondylitis ◽  
Bowel Disease ◽  
Lipocalin 2 ◽  
Inflammatory Bowel

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

2019 ◽  
Vol 8 (10) ◽  
pp. 1574 ◽  
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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