IF1 inactivation attenuates experimental colitis through downregulation of neutrophil infiltration in colon mucosa

Berberine (BER), a natural isoquinoline alkaloid, has been demonstrated to have appreciable anticolitis effects. Nevertheless, the protective mechanism of BER in ulcerative colitis (UC) is barely understood. The present study was aimed at exploring the therapeutic efficacy of BER on UC in experimental colitis rat model. Rats were orally administered with BER for seven days at low and high doses (25 and 50 mg/kg/day) before AcOH intracolonic instillation. BER significantly retrieved colon inflammation and mucosal damage indicated by inhibition of macroscopic score and lessened the levels of inflammatory biomarkers (IL-1β, IL-6, TNF-α, MPO, and PGE2). Notable downregulation of mRNA expression of p38 MAPK and increased protein expression of TGF-β were achieved by BER treatment. The anti-inflammatory potential of BER was supported by the histopathological screening of colon mucosa. In addition, BER restored colonic antioxidant capacity through elevation of GSH level and antioxidant enzymatic activities (SOD, CAT, GPx, and GR) together with reductions of both MDA and NO levels. Marked downregulation of Nos2 mRNA expression is accompanied by increased Nrf2 and Hmox-1 expressions in colon specimens treated by BER. Furthermore, BER exhibited noticeable antiapoptotic activities through decreasing proapoptotic proteins (Bax and caspase-3) and lessening antiapoptotic Bcl-2 protein in the colon mucosa. Based on these findings, BER may improve colitis markedly which may be mediated by its striking antioxidant, anti-inflammatory, and antiapoptotic properties.

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Lactobacillus paracaseiReduces Intestinal Inflammation in Adoptive Transfer Mouse Model of Experimental Colitis

Clinical and Developmental Immunology ◽

10.1155/2011/807483 ◽

2011 ◽

Vol 2011 ◽

pp. 1-13 ◽

Cited By ~ 18

Author(s):

Manuel Oliveira ◽

Nabil Bosco ◽

Genevieve Perruisseau ◽

Jeanne Nicolas ◽

Iris Segura-Roggero ◽

...

Keyword(s):

Mouse Model ◽

Adoptive Transfer ◽

Immune Modulation ◽

Intestinal Inflammation ◽

Experimental Colitis ◽

Neutrophil Infiltration ◽

Lactobacillus Paracasei ◽

Therapeutic Benefits

Studies showed that specific probiotics provide therapeutic benefits in inflammatory bowel disease.In vitroevidence suggested thatLactobacillus paracaseialso called ST11 (CNCM I-2116) is a potent strain with immune modulation properties. However, little is known about its capacity to alleviate inflammatory symptomsin vivoIn this context, the main objective of this study was to investigate the role of ST11 on intestinal inflammation using the adoptive transfer mouse model of experimental colitis. Rag2-/-recipient mice were fed with ST11 (109CFU/day)a month prior toinduce colitis by adoptive transfer of naive T cells. One month later, in clear contrast to nonfed mice, weight loss was significantly reduced by 50% in ST11-fed mice. Further analysis of colon specimens revealed a significant reduction neutrophil infiltration and mucosal expression of IL1β, IL-6, and IL12 proinflammatory cytokines, whereas no consistent differences in expression of antibacterial peptides or tight junction proteins were observed between PBS and ST11-fed mice. All together, our results demonstrate that oral administration of ST11 was safe and had a significant preventive effect on colitis. We conclude that probiotics such asLactobacillus paracaseiharbor worthwhilein vivoimmunomodulatory properties to prevent intestinal inflammation by nutritional approaches.

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Reduced oxidative and nitrosative damage in murine experimental colitis in the absence of inducible nitric oxide synthase

Gut ◽

10.1136/gut.45.2.199 ◽

1999 ◽

Vol 45 (2) ◽

pp. 199-209 ◽

Cited By ~ 83

Author(s):

B Zingarelli ◽

C Szabó ◽

A L Salzman

Keyword(s):

Nitric Oxide ◽

Nitrosative Stress ◽

Experimental Colitis ◽

Neutrophil Infiltration ◽

Intercellular Adhesion Molecule ◽

Myeloperoxidase Activity ◽

Wild Type ◽

Oxidative And Nitrosative Stress ◽

Intense Staining ◽

Genetic Ablation

BACKGROUNDOxidative and nitrosative stress have been implicated in the pathogenesis of inflammatory bowel diseases.AIMSTo study the role of nitric oxide (NO) derived from inducible NO synthase (iNOS) in an experimental model of murine enterocolitis.METHODSTrinitrobenzene sulphonic acid (TNBS) was instilled per rectum to induce a lethal colitis in iNOS deficient mice and in wild type controls. The distal colon was evaluated for histological evidence of inflammation, iNOS expression and activity, tyrosine nitration and malondialdehyde formation (as indexes of nitrosative and oxidative stress), myeloperoxidase activity (as index of neutrophil infiltration), and tissue localisation of intercellular adhesion molecule 1 (ICAM-1).RESULTSTNBS administration induced a high mortality and weight loss associated with a severe colonic mucosal erosion and ulceration, increased myeloperoxidase activity, increased concentrations of malondialdehyde, and an intense staining for nitrotyrosine and ICAM-1 in wild type mice. Genetic ablation of iNOS gene conferred to mice a significant resistance to TNBS induced lethality and colonic damage, and notably reduced nitrotyrosine formation and concentrations of malondialdehyde; it did not, however, affect neutrophil infiltration and intestinal ICAM-1 expression in the injured tissue.CONCLUSIONData show that activation of iNOS is required for nitrosative and oxidative damage in experimental colitis.

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A critical role of endothelial cell protein C receptor in the intestinal homeostasis in experimental colitis

Scientific Reports ◽

10.1038/s41598-020-77502-3 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Vijay Kondreddy ◽

Shiva Keshava ◽

Charles T. Esmon ◽

Usha R. Pendurthi ◽

L. Vijaya Mohan Rao

Keyword(s):

Endothelial Cell ◽

Epithelial Cells ◽

Protein C ◽

Factor Viia ◽

Activity Index ◽

Critical Role ◽

Experimental Colitis ◽

Cell Protein ◽

Bodyweight Loss ◽

Colon Mucosa

AbstractCrohn’s disease and ulcerative colitis are the two forms of disorders of the human inflammatory bowel disease with unknown etiologies. Endothelial cell protein C receptor (EPCR) is a multifunctional and multiligand receptor, which is expressed on the endothelium and other cell types, including epithelial cells. Here, we report that EPCR is expressed in the colon epithelial cells, CD11c+, and CD21+/CD35+ myeloid cells surrounding the crypts in the colon mucosa. EPCR expression was markedly decreased in the colon mucosa during colitis. The loss of EPCR appeared to associate with increased disease index of the experimental colitis in mice. EPCR−/− mice were more susceptible to dextran sulfate sodium (DSS)-induced colitis, manifested by increased weight loss, macrophage infiltration, and inflammatory cytokines in the colon tissue. DSS treatment of EPCR−/− mice resulted in increased bleeding, bodyweight loss, anemia, fibrin deposition, and loss of colon epithelial and goblet cells. Administration of coagulant factor VIIa significantly attenuated the DSS-induced colon length shortening, rectal bleeding, bodyweight loss, and disease activity index in the wild-type mice but not EPCR−/− mice. In summary, our data provide direct evidence that EPCR plays a crucial role in regulating the inflammation in the colon during colitis.

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P009 Fluorescence mediated tomography detects and quantifies early intestinal neutrophil infiltration in experimental colitis

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjy222.133 ◽

2019 ◽

Vol 13 (Supplement_1) ◽

pp. S090-S091

Author(s):

T M Nowacki ◽

P Lenz ◽

D Bettenworth ◽

M Brückner ◽

P Tepasse ◽

...

Keyword(s):

Experimental Colitis ◽

Neutrophil Infiltration

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Sa1844 The JAK1-Selective Inhibitor, Filgotinib, Reverses the Disease Signature of Colon Mucosa in Experimental Colitis

Gastroenterology ◽

10.1016/s0016-5085(16)31333-6 ◽

2016 ◽

Vol 150 (4) ◽

pp. S379 ◽

Cited By ~ 1

Author(s):

Mate Ongenaert ◽

Sonia Dupont ◽

Béatrice Vayssière ◽

Reginald Brys ◽

Rene Galien

Keyword(s):

Experimental Colitis ◽

Selective Inhibitor ◽

Colon Mucosa ◽

Disease Signature

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Corticotropin-Releasing Hormone Deficiency Is Associated with Reduced Local Inflammation in a Mouse Model of Experimental Colitis

Endocrinology ◽

10.1210/en.2007-1703 ◽

2008 ◽

Vol 149 (7) ◽

pp. 3403-3409 ◽

Cited By ~ 28

Author(s):

Jérôme Gay ◽

Efi Kokkotou ◽

Michael O’Brien ◽

Charalabos Pothoulakis ◽

Katia P. Karalis

Keyword(s):

Mouse Model ◽

Inflammatory Responses ◽

Inflammatory Diseases ◽

Experimental Colitis ◽

Neutrophil Infiltration ◽

Hormone Deficiency ◽

Trinitrobenzene Sulfonic Acid ◽

Inflammatory Bowel ◽

Proinflammatory Role ◽

Deficient Mice

CRH, the hypothalamic component of the hypothalamic-pituitary adrenal axis, attenuates inflammation through stimulation of glucocorticoid release, whereas peripherally expressed CRH acts as a proinflammatory mediator. CRH is expressed in the intestine and up-regulated in patients with ulcerative colitis. However, its pathophysiological significance in intestinal inflammatory diseases has just started to emerge. In a mouse model of acute, trinitrobenzene sulfonic acid-induced experimental colitis, we demonstrate that, despite low glucocorticoid levels, CRH-deficient mice develop substantially reduced local inflammatory responses. These effects were shown by histological scoring of tissue damage and neutrophil infiltration. At the same time, CRH deficiency was found to be associated with higher serum leptin and IL-6 levels along with sustained anorexia and weight loss, although central CRH has been reported to be a strong appetite suppressor. Taken together, our results support an important proinflammatory role for CRH during mouse experimental colitis and possibly in inflammatory bowel disease in humans. Moreover, the results suggest that CRH is involved in homeostatic pathways that link inflammation and metabolism.

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Lansoprazole a Proton Pump Inhibitor Prevents IBD by Reduction of Oxidative Stress and NO Levels in the Rat

Drug Research ◽

10.1055/a-1389-5499 ◽

2021 ◽

Author(s):

Tejal Gandhi ◽

Anish Sharma ◽

Navdha Vyas ◽

Parth Gupta ◽

Mihir Parikh ◽

...

Keyword(s):

Body Weight ◽

Proton Pump ◽

Damage Index ◽

Experimental Colitis ◽

Neutrophil Infiltration ◽

Sprague Dawley ◽

Colon Tissue ◽

Nitric Oxide Level ◽

Ameliorative Effect ◽

Anti Inflammatory

AbstractThe inflammatory disease’s increased prevalence leads to a major concern around the world. Still, there is a lack of effective and successful therapy in the reversal of Inflammatory Bowel Disease (IBD) symptoms. Whereas, reactive oxygen species (ROS) production and muddled defense capacity of antioxidants in IBD subjects reported several times. Many proton pump inhibitors have been reported previously for their anti-inflammatory effect. The present study is aimed to assess the ameliorative effect of lansoprazole in experimentally induced IBD in rats. Thirty-six female Sprague Dawley rats were divided equally into six groups based on their body weight. Lansoprazole (1, 5, and 10 mg/kg, p.o.) and 5-aminosalicylate (5-ASA, 100 mg/kg, p.o.) served as standard control respectively, given for 18 days once a day. On the 11th day of the study, colitis was induced by intrarectal instillation of 2, 4-Dinitrobenzene sulfonic acid (DNBS), and treatment was continued for the next 7 days. Administration of lansoprazole (at 5 and 10 mg/kg) significantly reduced DAI (Disease Activation Index) and CMDI (Colon Macroscopic Damage Index); which further justifies a reduction in colon inflammation grades, as well as histopathological changes, and reflected by the stalling of body weight. The anti-inflammatory effects were indicated by lowered MPO (myeloperoxidase) and SOD (superoxide dismutase) in colon tissue as well as restores colonic NO (nitric oxide) level. The study shows lansoprazole improved DAI and CMDI scores, reduction of neutrophil infiltration, and an improved antioxidant status indicating an anti-ulcerative effect in DNBS-induced experimental colitis that is comparable with 5-ASA treatment.

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Preventive effect of the microalgaChlamydomonas debaryanaon the acute phase of experimental colitis in rats

British Journal Of Nutrition ◽

10.1017/s0007114514001895 ◽

2014 ◽

Vol 112 (7) ◽

pp. 1055-1064 ◽

Cited By ~ 8

Author(s):

Javier Ávila-Román ◽

Elena Talero ◽

Antonio Alcaide ◽

Carolina de los Reyes ◽

Eva Zubía ◽

...

Keyword(s):

Body Weight Loss ◽

Experimental Colitis ◽

Active Phase ◽

Neutrophil Infiltration ◽

Oral Route ◽

Trinitrobenzenesulfonic Acid ◽

Subsequent Increase ◽

Mucus Production ◽

Microalgal Biomass ◽

Bowel Diseases

Inflammatory bowel diseases (IBD) are characterised by chronic uncontrolled inflammation of intestinal mucosa. Diet and nutritional factors have emerged as possible interventions for IBD. Microalgae are rich sources ofn-3 PUFA and derived oxylipins. Oxylipins are lipid mediators involved in the resolution of many inflammatory disorders. The aim of the present study was to investigate the effects of the oxylipin-containing biomass of the microalgaChlamydomonas debaryanaand its major oxylipin constituent, (9Z,11E,13S,15Z)-13-hydroxyoctadeca-9,11,15-trienoic acid ((13S)-HOTE), on acute 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. Lyophilised microalgal biomass and (13S)-HOTE were administered by oral route 48, 24 and 1 h before the induction of colitis and 24 h later, and the rats were killed after 48 h. The treatment with the lyophilised microalga and (13S)-HOTE improved body-weight loss and colon shortening, as well as attenuated the extent of colonic damage and increased mucus production. Cellular neutrophil infiltration, with the subsequent increase in myeloperoxidase levels induced by TNBS, were also reduced after the administration of the lyophilised microalga or (13S)-HOTE. The anti-inflammatory effects of these treatments were confirmed by the inhibition of colonic TNF-α production. Moreover, lyophilised microalga or (13S)-HOTE down-regulated cyclo-oxygenase-2 and inducible nitric oxide synthase expression. The present study was the first to show the prophylactic effects of a lyophilised biomass sample of the microalgaC. debaryanaand the oxylipin (13S)-HOTE on TNBS-induced acute colitis in rats. Our findings suggest that the microalgaC. debaryanaor derived oxylipins could be used as nutraceuticals in the treatment of the active phase of IBD.

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On the benefits of silymarin in murine colitis by improving balance of destructive cytokines and reduction of toxic stress in the bowel cells

Open Life Sciences ◽

10.2478/s11535-008-0053-2 ◽

2009 ◽

Vol 4 (2) ◽

pp. 204-213 ◽

Cited By ~ 10

Author(s):

Hadi Esmaily ◽

Azadeh Hosseini-Tabatabaei ◽

Reza Rahimian ◽

Reza Khorasani ◽

Maryam Baeeri ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Experimental Colitis ◽

Neutrophil Infiltration ◽

Distal Colon ◽

Male Rats ◽

Unknown Etiology ◽

Albino Rats ◽

Myeloperoxidase Activity ◽

Positive Treatment ◽

Anti Inflammatory

AbstractInflammatory bowel disease (IBD) is a multifactorial disease with an unknown etiology characterized by oxidative stress, leucocyte infiltration and a rise in inflammatory cytokines. In this study, we have investigated the effects of silymarin, a mixture of several flavonolignans with established antioxidant and anti-inflammatory properties, on trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. Experimental colitis was induced in male Wistar-albino rats by delivering TNBS to the distal colon. All the medicines were administered by gavage for seven days. Thirty-six male rats were divided into six groups containing six rats in each one. Control rats received only TNBS. In the treated groups, animals were given different doses of silymarin (40, 80, and 160 mg/kg). Dexamethasone (1 mg/kg) was used as the positive treatment. Colonic status was investigated seven days post induction of colitis through macroscopic, histological, and biochemical analyses. Amelioration of the morphological signs including macroscopic damage, necrotic area, and histology were seen subsequent to treating animals with silymarin. These observations were accompanied by a significant reduction in the degree of both neutrophil infiltration, indicated by decreased myeloperoxidase activity, and lipid peroxidation, as measured by a decline in malodialdehyde content in inflamed colon as well as a decrease in levels of inflammatory cytokines (TNF-α and IL-1β). The results of the present study reveal that the beneficial effect of silymarin in bowel cells is mediated through its anti-oxidant and anti-inflammatory potentials.

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