scholarly journals Amelioration of Colitis in Mouse Model by Exploring Antioxidative Potentials of an Indigenous Probiotic Strain ofLactobacillus fermentumLf1

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Ritu Chauhan ◽  
Aparna Sudhakaran Vasanthakumari ◽  
Harsh Panwar ◽  
Rashmi H. Mallapa ◽  
Raj Kumar Duary ◽  
...  

Based on the preliminary screening of eight indigenous putative probioticLactobacilli,Lactobacillus fermentumLf1 was selected for assessing its antioxidative efficacy in DSS colitis mouse model based on its ability to enhance the expression of “Nrf2” by 6.43-fold and malondialdehyde (MDA) inhibition by 78.1  ±  0.24% in HT-29 cells under H2O2stress. The Disease Activity Index and histological scores of Lf1-treated mice were lower than the control group. However, expression of “Nrf2” was not observed in Lf1-treated mice. A significant increase in the expression of antioxidative enzymes such asSOD2 andTrxR-1 was recorded in both of the groups. The expression ofSOD2 was significantly downregulated in colitis-induced mice by −100.00-fold relative to control group, and the downregulation was considerably reduced to −37.04-fold in colitis Lf1 treatment group. Almost, a similar trend was recorded in case of “thioredoxin” expression, though “CAT” was refractile to expression. The Lf1-treated group had decreased malondialdehyde level as compared to colitis control (37.92  ±  6.31 versus 91.13  ±  5.76 μM/g). These results point towards Lf1-induced activation of the antioxidant enzyme system in the mouse model and its prospects to be explored as a new strategy for IBD management.

Author(s):  
J. Santoantonio ◽  
L. Yazigi ◽  
E. I. Sato

The purpose of this study was to investigate the personality characteristics in adolescents with SLE. The research design is a case-control study by means of the Rorschach Method and the Wechsler Intelligence Scale. Study group: 30 female adolescents with lupus, 12–17 years of age. The SLE Disease Activity Index was administered during the period of psychological evaluation. Control group: 32 nonpatient adolescents were matched for age, sex, and socioeconomic level. In the Wechsler Intelligence Scale the mean IQ of the experimental group was significantly lower than that of the control group (77 and 98, respectively, p < .001). In the Rorschach, the lupus patients showed greater difficulty in interpersonal interactions, although they displayed the resources to process affect and to cope with stressful situations. A positive moderate correlation (p = .069) between the activity index of the disease and the affect constriction proportion of the Rorschach was observed: the higher the SLEDAI score, the lower the capacity to process affect. There is a negative correlation between the activity index of the disease and the IQ (p = .001): with a higher activity index of the disease, less intellectual resources are available.


Lupus ◽  
2020 ◽  
Vol 29 (2) ◽  
pp. 182-190
Author(s):  
W Batista Cicarini ◽  
R C Figueiredo Duarte ◽  
K Silvestre Ferreira ◽  
C de Mello Gomes Loures ◽  
R Vargas Consoli ◽  
...  

We have explored the relationship between possible hemostatic changes and clinical manifestation of the systemic lupus erythematosus (SLE) as a function of greater or lesser disease activity according to Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) criteria. Endothelial injury and hypercoagulability were investigated in patients with SLE by measuring thrombomodulin (TM), D-dimer (DDi) and thrombin generation (TG) potential. A total of 90 participants were distributed into three groups: 1) women with SLE presenting with low disease activity (laSLE) (SLEDAI-2K ≤ 4), 2) women with SLE presenting with moderate to high disease activity (mhaSLE) (SLEDAI-2K > 4), and 3) a control group comprising healthy women. Levels of TM and DDi were higher both in the laSLE and mhaSLE groups compared to controls and in mhaSLE compared to the laSLE group. With respect to TG assay, lagtime and endogen thrombin potential, low concentrations of tissue factor provided the best results for discrimination among groups. Analysis of these data allow us to conclude that TM, DDi and TG are potentially useful markers for discriminating patients with very active from those with lower active disease. Higher SLE activity may cause endothelial injury, resulting in higher TG and consequently a hypercoagulability state underlying the picture of thrombosis common in this inflammatory disease.


2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Dong Ki Park ◽  
Hye-Jin Park

The effect ofCordyceps militaris(CM) grown on germinated soybeans (GSC) in the inflammatory bowel disease (IBD) model was studied. To demonstrate the preventive effect of GSC extract in a dextran-sodium-sulfate- (DSS-) induced acute colitis mouse model, GSC was administered 2 days before DSS coadministration. GSC significantly suppressed DSS-induced disease activity index (DAI) as well as histopathological scores, compared to control or CM-treated group. To elucidate the anti-IBD activity of GSC, we checked the level of matrix metalloproteinases (MMPs) and inflammatory mediators. GSC extract decreased the level of MMP-3 and -9 mRNAs and p53 proteins. The level and activity of LPS-induced MMP-9 were reduced in GSC-treated RAW264.7 cells. It also attenuated the level of inducible nitric oxide synthase (iNOS) and tumor necrosis factor- (TNF-)αmRNAs both in colon tissue and in macrophage cells. These results suggest that GSC can be applied as a protective agent against IBDs.


Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1684 ◽  
Author(s):  
Larissa Celiberto ◽  
Roseli Pinto ◽  
Elizeu Rossi ◽  
Bruce Vallance ◽  
Daniela Cavallini

Modulation of the gut microbiota through the use of probiotics has been widely used to treat or prevent several intestinal diseases. However, inconsistent results have compromised the efficacy of this approach, especially in severe conditions such as inflammatory bowel disease (IBD). The purpose of our study was to develop a personalized probiotic strategy and assess its efficacy in a murine model of intestinal inflammation. Commensal bacterial strains were isolated from the feces of healthy mice and then administered back to the host as a personalized treatment in dextran sodium sulfate (DSS)-induced colitis. Colonic tissues were collected for histological analysis and to investigate inflammatory markers such as Il-1β, Il-6, TGF-β, and Il-10, and the enzyme myeloperoxidase as a neutrophil marker. The group that received the personalized probiotic showed reduced susceptibility to DSS-colitis as compared to a commercial probiotic. This protection was characterized by a lower disease activity index and reduced histopathological damage in the colon. Moreover, the personalized probiotic was more effective in modulating the host immune response, leading to decreased Il-1β and Il-6 and increased TGF-β and Il-10 expression. In conclusion, our study suggests that personalized probiotics may possess an advantage over commercial probiotics in treating dysbiotic-related conditions, possibly because they are derived directly from the host’s own microbiota.


2020 ◽  
Vol 58 (5) ◽  
pp. 503-511
Author(s):  
O. A. Krichevskaya ◽  
Z. M. Gandaloeva ◽  
S. I. Glukhova ◽  
I. Yu. Skripkina ◽  
A. B. Demina ◽  
...  

Objective: Assessment of ankylosing spondylitis activity patterns during pregnancy using BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and ASDAS-CRP (Ankylosing Spondylitis Disease Activity Score — C-Reactive Protein) disease activity indices.Materials and methods. The prospective study included 36 pregnant women with AS (modified New York AS criteria, 1984). Patients’ mean age was 31.6±4.8 years, mean age at AS onset was 21.8±10.9, and disease duration 134.9±89.3 months. The control group included 30 healthy pregnant women with no history of back pain and arthritis, their mean age was 28.2±4.5 years. In the I trimester of pregnancy 10 (33.3%) As patients experienced back pain, while in the III trimester already 15 (50%) had back pain. Throughout pregnancy, the intensity of back pain in the I, II и III trimesters based on numeric scale was on average 1.9±0.9; 2.1±1.1 and 2.1±0.8. BASDAI and ASDAS-CRP were used to measure disease activity on gestational Weeks 10–11, 20–21 and 31–32. The time of conception BASDAI score was assessed retrospectively at the 1st visit.Results and discussion. BASDAI mean values at the time of conception and I, II и III trimesters of pregnancy were: 2.3±1.9; 2.8±1.72 (p<0,05 vs month of conception); 3.2±1.9 and 3.3±2.1 respectively. Mean ASDAS-CRP in the I, II и III trimesters were 1.9±0.7; 2.3±0.9 and 2.2±0,8 respectively. There was a trend to CRP increase in the II and III trimesters vs the I: median CRP values in the I, II and III trimesters were 5.7 [1.6; 6.2], 8.0 [2.1; 9.6] and 7.9 [2.0; 9.2] mg/L, respectively. Percentages of patients with high disease activity based on BASDAI scores in the I, II and III trimesters were 30.6; 34.3 and 34.3%; based on ASDAS-CRP — 36.1; 57.5 and 53%, respectively. Throughout pregnancy, BASDAI scores were lower in the control group than in AS patients (p<0.01). However, no differences were found when comparing BASDAI values of AS patients and healthy women with back pain during pregnancy. The level of fatigue did not differ between pregnant women with AS (median 5[3; 7] and 5[3; 6]) and healthy controls (5[3; 8] and 5[4; 6]) in the I and II trimesters, while in the III trimester, fatigue in healthy pregnant women (6[4; 8]) was more pronounced than in AS patients (5[3; 6], p=0.01). Throughout pregnancy, the intensity of back pain in AS patients and healthy pregnant women with back pain did not differ (p<0.05). Median pain intensity in the I, II and III trimesters was 3[2; 4]; 4[3; 5]; 3[2; 6] and 2,5[1; 4]; 3[2; 7]; 4[2; 6], respectively. A high (rs ≥0,7) correlation of all BASDAI components with the index itself in each trimester of pregnancy, except for joint pain in the month of conception, and in the I and III trimesters was established in the group of pregnant women with AS. The control group had quite high correlation (rs >0.7) of fatigue severity with the BASDAI index in the I and II trimesters of pregnancy and moderate correlation (rs >0.53) in the III trimester; as wells as moderate (rs >0.5-0.69) correlation between back pain and BASDAIConclusion. A trend towards increasing AS activity based on BASDAI and ASDAS-CRP scores and CRP levels was established for the first half of pregnancy. Later in pregnancy these increased values failed to return to normal until the end of gestation. The percentage of AS patients with highto-moderate disease activity throughout pregnancy was lower based on BASDAI score vs based on ASDAS-CRP. Some BASDAI components (fatigue and back pain) reflect not only the activity of AS, but also changes associated with physiological pregnancy. The BASDAI index requires adaptation for use in pregnancy


2014 ◽  
Vol 51 (2) ◽  
pp. 107-112 ◽  
Author(s):  
Luiz Gustavo de OLIVEIRA ◽  
André Luiz da CUNHA ◽  
Amaury Caiafa DUARTE ◽  
Maria Christina Marques Nogueira CASTAÑON ◽  
Júlio Maria Fonseca CHEBLI ◽  
...  

ContextInflammatory bowel disease, including ulcerative colitis and Crohn’s disease, comprising a broad spectrum of diseases those have in common chronic inflammation of the gastrointestinal tract, histological alterations and an increased activity levels of certain enzymes, such as, metalloproteinases.ObjectivesEvaluate a possible correlation of disease activity index with the severity of colonic mucosal damage and increased activity of metalloproteinases in a model of ulcerative colitis induced by dextran sulfate sodium.MethodsColitis was induced by oral administration of 5% dextran sulfate sodium for seven days in this group (n=10), whereas control group (n=16) received water. Effects were analyzed daily by disease activity index. In the seventh day, animals were euthanized and hematological measurements, histological changes (hematoxylin and eosin and Alcian Blue staining), myeloperoxidase and metalloproteinase activities (MMP-2 and MMP-9) were determined.ResultsDextran sulfate sodium group showed elevated disease activity index and reduced hematological parameters. Induction of colitis caused tissue injury with loss of mucin and increased myeloperoxidase (P<0.001) and MMP-9 activities (45 fold) compared to the control group.ConclusionsIn this study, we observed a disease activity index correlation with the degree of histopathological changes after induction of colitis, and this result may be related mainly to the increased activity of MMP-9 and mieloperoxidase.


2009 ◽  
Vol 296 (6) ◽  
pp. G1167-G1179 ◽  
Author(s):  
Ryan Ungaro ◽  
Masayuki Fukata ◽  
David Hsu ◽  
Yasmin Hernandez ◽  
Keith Breglio ◽  
...  

Dysregulated innate immune responses to commensal bacteria contribute to the development of inflammatory bowel disease (IBD). TLR4 is overexpressed in the intestinal mucosa of IBD patients and may contribute to uncontrolled inflammation. However, TLR4 is also an important mediator of intestinal repair. The aim of this study is to examine the effect of a TLR4 antagonist on inflammation and intestinal repair in two murine models of IBD. Colitis was induced in C57BL/6J mice with dextran sodium sulfate (DSS) or by transferring CD45Rbhi T cells into RAG1−/− mice. An antibody (Ab) against the TLR4/MD-2 complex or isotype control Ab was administered intraperitoneally during DSS treatment, recovery from DSS colitis, or induction of colitis in RAG1−/− mice. Colitis severity was assessed by disease activity index (DAI) and histology. The effect of the Ab on the inflammatory infiltrate was determined by cell isolation and immunohistochemistry. Mucosal expression of inflammatory mediators was analyzed by real-time PCR and ELISA. Blocking TLR4 at the beginning of DSS administration delayed the development of colitis with significantly lower DAI scores. Anti-TLR4 Ab treatment decreased macrophage and dendritic cell infiltrate and reduced mucosal expression of CCL2, CCL20, TNF-α, and IL-6. Anti-TLR4 Ab treatment during recovery from DSS colitis resulted in defective mucosal healing with lower expression of COX-2, PGE2, and amphiregulin. In contrast, TLR4 blockade had minimal efficacy in ameliorating inflammation in the adoptive transfer model of chronic colitis. Our findings suggest that anti-TLR4 therapy may decrease inflammation in IBD but may also interfere with colonic mucosal healing.


2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S6-S6
Author(s):  
Diane Peters ◽  
Lauren Norris ◽  
Barbara Slusher

Abstract Background Glutamate carboxypeptidase II (GCPII) is highly upregulated in human IBD and is a therapeutic target under active investigation by our laboratory. We recently published that a spontaneously occurring loss-of-function mutation in dedicator of cytokinesis 2 (Dock2Hsd) that was present in commercially-purchased “wild-type” C57Bl6/NHsd mice increased their sensitivity to DSS-colitis and caused them to closely resemble human IBD with respect to GCPII. The DSS-exposed Dock2Hsd mice had significantly elevated colon GCPII activities and were sensitive to treatment with the GCPII inhibitor, 2-PMPA. We hypothesized that if colitis of the same severity were to be induced in Dock2WT mice, that they would also exhibit heightened colon GCPII activity and would be equally sensitive to 2-PMPA treatment. Methods DSS-colitis was induced in weight-, age- and gender-matched C57Bl/6NHsd mice (Dock2Hsd and Dock2WT). Increasing concentrations of DSS were utilized (2.5%-4.0%) and disease activity index was monitored daily. Mice received once daily treatment with vehicle or GCPII inhibitor 2-PMPA (IP). Results With increased DSS concentrations (4%), a severe colitis could be established in the Dock2WT mice which closely resembled the disease seen in Dock2Hsd mice induced with 2.5% DSS. Interestingly, despite similarity in DAI scores and disease progression, the GCPII activity in colons of Dock2WT mice (4% DSS) remained significantly lower than that of Dock2Hsd mice (2.5% DSS) (p&lt;0.001, t-test). Further, while 2-PMPA was effective in both groups, higher systemic doses were required in the IBD-resistant Dock2WT mice. Conclusions Following identification that the spontaneously occurring mutation Dock2Hsd influences murine DSS-colitis sensitivity and alters the activity of our therapeutic target protein, GCPII, in the colon, we sought to re-establish our DSS model using Dock2WT mice. While we were successfully able to recapitulate disease severity in the Dock2WT mice by increasing the DSS concentration from 2.5% to 4%, the underlying disease biology was not conserved. Despite having comparable DAI scores at study termination, Dock2WT mice had decreased GCPII activity in their colons relative to Dock2Hsd mice and were less sensitive to inhibition with the GCPII inhibitor, 2-PMPA. These data caution that target protein expression must be verified even with subtle changes to experimental method when utilizing the DSS-colitis model.


2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S137-S137
Author(s):  
F WEIß ◽  
I F M Lee ◽  
A Fromm ◽  
J C E Hu ◽  
T Breiderhoff ◽  
...  

Abstract Background In Inflammatory bowel disease, intestinal homeostasis cannot be sustained due to an overreaction of the immune system and a disturbed epithelial barrier due to an impaired tight junction (TJ). At tricellular TJs (tTJs), which are formed where three cells meet, the TJ network is basolaterally expanded and forms a central tube which would be potentially large enough to allow for a paracellular passage of macromolecules. Under normal conditions, the tTJ protein tricellulin (Tric) seals the central tube against luminal uptake. However, in ulcerative colitis (UC), Tric is downregulated, resulting in increased uptake of macromolecules including antigens which may further support the inflammatory processes. Thus, we aimed to identify whether or not overexpression of Tric has a protective effect against inflammation. Methods We generated intestinal epithelial cell-specific overexpression of Tric in mice (B6.C-Tg(Vil-cre) Rosa26tgGFP-Tric). In Tric-overexpressing (Tric-OE) and in wild-type (wt) mice experimental colitis was induced by 3% dextran sodium sulphate (DSS) for 6 days. The effect was assessed by determining the disease activity index (DAI: weight loss, stool consistency, and stool bleeding) and the colon dimensions. Using chamber experiments were performed to determine permeabilities for ions and macromolecules of different sizes (4 and 10 kDa). Results No difference in weight loss was observed between wt and Tric-OE mice upon DSS treatment. However, Tric-OE mice suffered less from diarrhoea and had less bloody stools compared with wt mice resulting in a lower DAI. In addition, DSS caused a reduced colon length which was less prominent in Tric-OE mice than in wt mice. Functional analysis revealed higher permeabilities for Na+ and Cl− after DSS treatment with no significant differences between Tric-OE and wt mice. In contrast, permeabilities for macromolecules of both sizes were unchanged after DSS treatment in Tric-OE mice but elevated in wt-mice. Conclusion Tric-overexpression prevents the epithelial barrier from elevated paracellular uptake of macromolecules during DSS colitis without affecting ion permeability. This protects against DSS colitis as indicated by less affected clinical and structural outcome parameters, most likely via a reduction in a load of immunologically active macromolecules in the subepithelium.


2020 ◽  
Vol 21 (22) ◽  
pp. 8551
Author(s):  
Evelyn L. Kerber ◽  
Claudia Padberg ◽  
Nora Koll ◽  
Vera Schuetzhold ◽  
Joachim Fandrey ◽  
...  

(1) Background: Hypoxia is a common feature of inflammation when hypoxia inducible factors (HIFs) adapt cells to conditions of low oxygen tension and inflammation. We studied the role of HIF-1 and HIF-2 in cells of the myeloid lineage in a mouse model of acute colitis. (2) Methods: Mice with and without a conditional knockout for either Hif-1a or Hif-2a or Hif-1a and Hif-2a in cells of the myeloid lineage were treated with 2.5% dextran sodium sulfate (DSS) for 6 days to induce an acute colitis. We analyzed the course of inflammation with respect to macroscopic (disease activity index) and microscopic (histology score and immunohistochemical staining of immune cells) parameters and quantified the mRNA expression of cytokines and chemokines in the colon and the mesenteric lymph nodes. (3) Results: A conditional knockout of myeloid Hif-1a ameliorated whereas the knockout of Hif-2a aggravated murine DSS colitis by increased recruitment of neutrophils to deeper layers of the colon. This led to higher expression of Il6, Ifng, Cd11c, Cd4, and Cd8 in the colon but also induced anti-inflammatory mediators such as Foxp3 and Il10. A conditional knockout of Hif-1a and Hif-2a did not show any differences compared to wildtype mice. (4) Conclusions: Myeloid HIF-1α and HIF-2α play opposing roles in acute DSS colitis. Thus, not only a cell type specific, but also the isoform specific modulation of HIFs needs to be addressed in attempts to modify HIF for therapeutic purposes.


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