scholarly journals Preventative oral methylthioadenosine is anti-inflammatory and reduces DSS-induced colitis in mice

2012 ◽  
Vol 303 (1) ◽  
pp. G71-G82 ◽  
Author(s):  
Nancy M. Benight ◽  
Barbara Stoll ◽  
Juan C. Marini ◽  
Douglas G. Burrin
Keyword(s):  
Time Course ◽  
Intestinal Inflammation ◽  
Tissue Injury ◽  
Experimental Colitis ◽  
Therapeutic Benefit ◽  
The Body ◽  
Myeloperoxidase Activity ◽  
Matrix Remodeling ◽  
Inflammatory Models ◽  
Anti Inflammatory

Methylthioadenosine (MTA) is a precursor of the methionine salvage pathway and has been shown to have anti-inflammatory properties in various models of acute and chronic inflammation. However, the anti-inflammatory properties of MTA in models of intestinal inflammation are not defined. We hypothesized that orally administered MTA would be bioavailable and reduce morbidity associated with experimental colitis. We examined clinical, histological, and molecular markers of disease in mice provided oral MTA before (preventative) or after (therapy) the induction of colitis with 3% dextran sulfate sodium (DSS). We found a reduction in disease activity, weight loss, myeloperoxidase activity, and histological damage in mice given preventative MTA compared with DSS alone. We also found that equivalent supplementation with methionine could not reproduce the anti-inflammatory effects of MTA, and that MTA had no detectable adverse effects in control or DSS mice. Expression microarray analysis of colonic tissue showed several dominant pathways related to inflammatory cytokines/chemokines and extracellular matrix remodeling were upregulation by DSS and suppressed in MTA-supplemented mice. MTA is rapidly absorbed in the gastrointestinal tract and disseminated throughout the body, based on a time course analysis of an oral bolus of MTA. This effect is transient, with MTA levels falling to near baseline within 90 min in most organs. Moreover, MTA did not lead to increased blood or tissue methionine levels, suggesting that its effects are specific. However, MTA provided limited therapeutic benefit when administered after the onset of colitis. Our results show that oral MTA supplementation is a safe and effective strategy to prevent inflammation and tissue injury associated with DSS colitis in mice. Additional studies in chronic inflammatory models are necessary to determine if MTA is a safe and beneficial option for the maintenance of remission in human inflammatory bowel disease.

scholarly journals Intestinal Anti-Inflammatory Activity of the Aqueous Extract from Ipomoea asarifolia in DNBS-Induced Colitis in Rats

2018 ◽  
Vol 19 (12) ◽  
pp. 4016 ◽  
Author(s):  
Valéria da Silva ◽  
Aurigena de Araújo ◽  
Daline Araújo ◽  
Maíra Lima ◽  
Roseane Vasconcelos ◽  
...  
Keyword(s):  
Protective Effect ◽  
Aqueous Extract ◽  
Intestinal Inflammation ◽  
Activity Index ◽  
Immunohistochemical Analysis ◽  
Histological Evaluation ◽  
Myeloperoxidase Activity ◽  
Down Regulation ◽  
Anti Inflammatory ◽  
Ipomoea Asarifolia

Inflammatory bowel disease is triggered by an uncontrolled immune response associated with genetic, environmental, and intestinal microbiota imbalance. Ipomoea asarifolia (IA), popularly known as “salsa” or “brave salsa”, belongs to the Convolvulaceae family. The aim of this approach was to study the preventive effect of IA aqueous extract in 2,4-dinitrobenzene sulfonic acid (DNBS)-induced colitis in rats. Rats pretreated with IA extract or sulfasalazine (SSZ) received intracolonic instillation of DNBS in 50% ethanol (v/v). IA extract presented a protective effect against intestinal inflammation, with improvement in the disease activity index and macroscopic damage. IA or SSZ significantly reduced myeloperoxidase activity, and also down-regulation of the gene expression of JNK1, NF-κβ-p65, STAT3, and decreased levels of TNFα, IL-1β, and increased IL-10, associated with a significant improvement of oxidative stress, in addition to a reduction in MDA and an increase of glutathione in colonic tissue. The protective effect of the extract was also confirmed in histological evaluation, showing preservation of the colonic cytoarchitecture. Immunohistochemical analysis revealed down-regulation of NF-κβ-p65, iNOS, IL-17, and up-regulation of SOCs-1 and MUC-2. IA extract presents antioxidant and anti-inflammatory intestinal properties, and proved to be a potential application for preventing damage induced by DNBS.

Expression and secretion of lipocortin 1 in gut inflammation are not regulated by pituitary-adrenal axis

1997 ◽  
Vol 273 (2) ◽  
pp. R623-R629 ◽  
Author(s):  
N. Vergnolle ◽  
C. Comera ◽  
J. More ◽  
M. Alvinerie ◽  
L. Bueno
Keyword(s):  
Culture Medium ◽  
Experimental Colitis ◽  
Myeloperoxidase Activity ◽  
Trinitrobenzenesulfonic Acid ◽  
Gut Inflammation ◽  
Adrenal Axis ◽  
Histological Damage ◽  
Anti Inflammatory ◽  
Pituitary Adrenal Axis

Lipocortin 1 is considered a mediator of the anti-inflammatory actions of glucocorticoids. We have shown that this protein is overexpressed and secreted during an experimental colitis induced by intraluminal injection of trinitrobenzenesulfonic acid (TNBS) in rats. We studied here the in vivo regulation of lipocortin 1 expression and secretion in this model, either by glucocorticoids using adrenalectomized or dexamethasone-treated (3 mg/24 h) animals or by pituitary factors using hypophysectomized animals. Inflammation was evaluated by measuring myeloperoxidase activity and by histological scoring of the damage. Lipocortin 1 was detected by immunoblotting, and its secretion was studied by incubating colonic specimens in-culture medium. In the colon of TNBS-injected animals, cumulative histological damage scores were increased in adrenalectomized and decreased in dexamethasone-treated animals compared with control and hypophysectomized animals. The colons of all TNBS-injected animals (controls, adrenalectomized, dexamethasone treated, hypophysectomized) overexpressed and secreted lipocortin 1. In conclusion, the induction of lipocortin 1 overexpression and secretion during this colitis occurs independently of glucocorticoids or pituitary factors.

scholarly journals Anti-Inflammatory Effects of Rosmarinus officinalis Essential Oil in Mice

2009 ◽  
Vol 78 (1) ◽  
pp. 121-127 ◽  
Author(s):  
Štefan Juhás ◽  
Alexandra Bukovská ◽  
Štefan Čikoš ◽  
Soňa Czikková ◽  
Dušan Fabian ◽  
...  
Keyword(s):  
Body Weight ◽  
Essential Oil ◽  
Weight Ratio ◽  
Rosmarinus Officinalis ◽  
The Body ◽  
Trinitrobenzene Sulfonic Acid ◽  
Myeloperoxidase Activity ◽  
Paw Oedema ◽  
Anti Inflammatory ◽  
Rosemary Essential Oil

Essential oils are plant secondary metabolites possessing various pharmacological properties, primarily anti-oxidative, antimicrobial or immunomodulative, but they can exhibit toxic and allergic effects as well. The aim of this study was to compare the effects of Rosmarinus officinalis essential oil dietary administration in carrageenan paw oedema and trinitrobenzene sulfonic acid (TNBS) colitis. ICR mice received rosemary essential oil at three concentrations (1 250, 2 500 and 5 000 ppm) in the standard laboratory diet starting two weeks before the experiments. The inflammation of paws induced by carrageenan application was evaluated by measurement of paw swelling, paw weight and myeloperoxidase activity. In the TNBS model the mice were killed by cervical dislocation 3 days after colitis induction and the mortality, changes in the body weight of mice, colon weight : body weight ratio, macroscopical scores and myeloperoxidase activity were analysed. Furthermore, IL-1β and IL-6 cytokine levels in colonic tissue were quantified using ELISA assay. Dietary supplementation with 5 000 ppm of rosemary essential oil initially after 2 h increased but after 24 h suppressed the extent of paw oedema. The same dose in the TNBS model exhibited protective effects on colonic mucosa and significantly decreased macroscopic scores for colonic inflammation. On the other hand, in colon samples from mice fed the diet with 1 250 ppm of rosemary essential oil we detected decreased myeloperoxidase activity and significantly lower levels of IL-6 compared to TNBS control animals. Our results indicate that rosemary essential oil is able to influence several variables of murine experimental inflammatory models depending on the concentration used. We conclude that the anti-inflammatory effects of rosemary essential oil should be interpreted carefully due to its timeand dose-related effects.

scholarly journals The Anti-Inflammatory Role of Bilirubin on “Two-Hit” Sepsis Animal Model

2020 ◽  
Vol 21 (22) ◽  
pp. 8650
Author(s):  
Duc Tin Tran ◽  
Yong Yeon Jeong ◽  
Jeong Min Kim ◽  
Hong Bum Bae ◽  
Sung Kuk Son ◽  
...  
Keyword(s):  
Animal Model ◽  
Inflammatory Cytokines ◽  
Tissue Injury ◽  
Antioxidant Properties ◽  
Cecal Ligation ◽  
Suppressor Cells ◽  
Inflammatory Cells ◽  
The Body ◽  
Sepsis Model ◽  
Anti Inflammatory

Introduction: Bilirubin is a product of the heme catabolism pathway, and it is excreted in bile and removed from the body through the urine. Bilirubin has potent antioxidant properties but also plays a role in anti-inflammation by protecting the body against endotoxin-induced lung inflammation, down-regulating the expression of adhesion molecules, and inhibiting the infiltration of inflammatory cells. Thus, bilirubin is a promising agent that could use in inflammation disease treatment. The application of bilirubin on the “two-hit” sepsis animal model has been, to date, unknown. Methods: we used lipopolysaccharide to induce initial insults in C57BL/6 mice. After 24 h, mice underwent cecal ligation and puncture to induce the “two-hit” sepsis model. Next, mice were administered 30 mg/kg bilirubin and we observed an improvement. Results: We observed that bilirubin inhibited the expression of pro-inflammatory cytokines, while the levels of anti-inflammatory cytokines were significantly augmented in the lung. Bilirubin improved the survival rate in the sepsis model. Furthermore, we suggest that bilirubin can modulate the accumulation of T-regulatory cells and myeloid-derived suppressor cells. Notably, bilirubin suppressed the activation and functions of T-cells. Conclusions: These results clarified that bilirubin might improve tissue injury in sepsis through anti-inflammatory mechanisms.

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

2009 ◽  
Vol 4 (2) ◽  
pp. 204-213 ◽  
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.

Rosmarinus officinalis L. extract ameliorates intestinal inflammation through MAPKs/NF-κB signaling in a murine model of acute experimental colitis

2016 ◽  
Vol 7 (7) ◽  
pp. 3233-3243 ◽  
Author(s):  
Kanakaraju Medicherla ◽  
Avanee Ketkar ◽  
Bidya Dhar Sahu ◽  
Godi Sudhakar ◽  
Ramakrishna Sistla
Keyword(s):  
Murine Model ◽  
Intestinal Inflammation ◽  
Experimental Colitis ◽  
Rosmarinus Officinalis ◽  
Anti Inflammatory ◽  
Rosmarinus Officinalis L

Anti-inflammatory and anti-colitis effects of Rosmarinus officinalis L. extract (RE).

scholarly journals Probiotic lactobacilli as a promising strategy to ameliorate disorders associated with intestinal inflammation induced by a non-steroidal anti-inflammatory drug

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
María José Martínez Monteros ◽  
Carolina Maldonado Galdeano ◽  
María Florencia Balcells ◽  
Ricardo Weill ◽  
Juan Andrés De Paula ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Small Intestine ◽  
Intestinal Inflammation ◽  
Body Weight Loss ◽  
The Body ◽  
Probiotic Supplementation ◽  
Severe Condition ◽  
Conventional Diet ◽  
Anti Inflammatory ◽  
Probiotic Lactobacilli

AbstractDamage to the small intestine caused by non-steroidal anti-inflammatory drugs (NSAIDs) occurs more frequently than in the upper gastrointestinal tract, is more difficult to diagnose and no effective treatments exist. Hence, we investigated whether probiotics can control the onset of this severe condition in a murine model of intestinal inflammation induced by the NSAID, indomethacin. Probiotic supplementation to mice reduce the body weight loss, anemia, shortening of the small intestine, cell infiltration into the intestinal tissue and the loss of Paneth and Goblet cells associated with intestinal inflammation. Furthermore, a high antimicrobial activity in the intestinal fluids of mice fed with probiotics compared to animals on a conventional diet was elicited against several pathogens. Interestingly, probiotics dampened the oxidative stress and several local and systemic markers of an inflammatory process, as well as increased the secretion of IL-10 by regulatory T cells. Even more importantly, probiotics induced important changes in the large intestine microbiota characterized by an increase in anaerobes and lactobacilli, and a significant decrease in total enterobacteria. We conclude that oral probiotic supplementation in NSAID-induced inflammation increases intestinal antimicrobial activity and reinforces the intestinal epithelial barrier in order to avoid pathogens and commensal invasion and maintain intestinal homeostasis.

scholarly journals Peroxisome Proliferator-Activated Receptor Alpha Mediates the Beneficial Effects of Atorvastatin in Experimental Colitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Paulo José Basso ◽  
Helioswilton Sales-Campos ◽  
Viviani Nardini ◽  
Murillo Duarte-Silva ◽  
Vanessa Beatriz Freitas Alves ◽  
...  
Keyword(s):  
Intestinal Inflammation ◽  
Experimental Colitis ◽  
Predictive Biomarker ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
Beneficial Effects ◽  
Anti Inflammatory

The current therapeutic options for Inflammatory Bowel Diseases (IBD) are limited. Even using common anti-inflammatory, immunosuppressive or biological therapies, many patients become unresponsive to the treatments, immunosuppressed or unable to restrain secondary infections. Statins are cholesterol-lowering drugs with non-canonical anti-inflammatory properties, whose underlying mechanisms of action still remain poorly understood. Here, we described that in vitro atorvastatin (ATO) treatment was not toxic to splenocytes, constrained cell proliferation and modulated IL-6 and IL-10 production in a dose-dependent manner. Mice exposed to dextran sulfate sodium (DSS) for colitis induction and treated with ATO shifted their immune response from Th17 towards Th2, improved the clinical and histological aspects of intestinal inflammation and reduced the number of circulating leukocytes. Both experimental and in silico analyses revealed that PPAR-α expression is reduced in experimental colitis, which was reversed by ATO treatment. While IBD patients also downregulate PPAR-α expression, the responsiveness to biological therapy relied on the restoration of PPAR-α levels. Indeed, the in vitro and in vivo effects induced by ATO treatment were abrogated in Ppara-/- mice or leukocytes. In conclusion, the beneficial effects of ATO in colitis are dependent on PPAR-α, which could also be a potential predictive biomarker of therapy responsiveness in IBD.

scholarly journals Purinergic P2X7 receptor antagonist ameliorates intestinal inflammation in postoperative ileus

2021 ◽  
Author(s):  
Hitomi Kimura ◽  
Takako Yamazaki ◽  
Taiki Mihara ◽  
Noriyuki Kaji ◽  
Masatoshi Hori
Keyword(s):  
P2x7 Receptor ◽  
Postoperative Ileus ◽  
Intestinal Inflammation ◽  
Tissue Injury ◽  
Inflammatory Cells ◽  
Neutrophil Infiltration ◽  
Muscle Layer ◽  
Chemically Induced ◽  
Purinergic P2x7 Receptor ◽  
Anti Inflammatory

Abstract Postoperative ileus (POI) is gastrointestinal motility dysfunction after abdominal surgery caused by mechanical stress to intestine. It occurs nausea and vomiting, and lead to lower QOL during hospitalization for patients. It is regarded as a problem because it costs medical expenses due to long hospitalization. The intestinal inflammation caused by macrophage and neutrophil is thought to be important of the mechanism of POI. In tissue injury or inflammation, adenosine triphosphate (ATP) is released from injured cell. Purinergic P2X7 receptor (P2X7R) is expressed on inflammatory cells and ATP induces the secretion of inflammatory mediators through P2X7R. P2X7R antagonist is thought to be important in the first step of inflammation, and it is confirmed that P2X7R antagonist showed anti-inflammatory effects in chemically-induced colitis models. Therefore, we hypothesized that P2X7R has important function in POI and examined the effect of P2X7R antagonist in mouse POI model. As a result, P2X7R antagonist A438079 ameliorated macrophage and neutrophil infiltration in POI. The impairment of intestinal transit was improved by P2X7R antagonist. It tended to ameliorate the increase of IL-6, IL-1β and TNF-α mRNA expression in intestinal muscularis caused by POI. P2X7R expressed on both infiltrated and resident macrophages in the inflamed ileal muscle layer. In conclusion, P2X7R antagonist showed the anti-inflammatory effect through P2X7R on macrophages, and it may be the target to treat POI.

scholarly journals Cell-extrinsic autophagy in mature adipocytes regulates anti-inflammatory response to intestinal tissue injury through lipid mobilization

2021 ◽  
Author(s):  
Felix Clemens Richter ◽  
Matthias Friedrich ◽  
Mathilde Pohin ◽  
Ghada Alsaleh ◽  
Irina Guschina ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Tissue Injury ◽  
Inflammatory Diseases ◽  
Protective Effects ◽  
Adipose Tissue Macrophages ◽  
Anti Inflammatory ◽  
Major Nutrients

Autophagy is a critical cellular recycling pathway which is genetically linked to the development of intestinal inflammation in humans. Inflammation drives adipose tissue breakdown and provision of major nutrients such as free fatty acids (FFA). However, the effect of autophagy-mediated FFA release by adipocytes in immune-mediated inflammatory diseases remains unexplored. In a mouse model of intestinal inflammation, we found that visceral adipocytes upregulate autophagy at peak inflammation. Adipocyte-specific loss of the key autophagy gene Atg7 (Atg7Ad) resulted in the exacerbation of intestinal inflammation. TNFα-induced lipolysis was impaired in Atg7-deficient adipocytes leading to the reduced availability of several FFA species, and decreased expression of the FFA transporter CD36 on adipose tissue macrophages (ATMs). Visceral adipose tissues from Atg7Ad mice released less IL-10 resulting in lower levels of circulating IL-10 in colitis. ATMs present the main source of adipose tissue-derived IL-10 during colitis. In vitro assays confirmed that FFA restriction from macrophages reduced CD36 expression and diminished IL-10 production. Taken together, our study demonstrates that autophagy-mediated FFA release from adipocytes directs anti-inflammatory responses in ATMs, which in turn conveys protective effects for distant intestinal inflammation.

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