Dietary diosgenin attenuates subacute intestinal inflammation associated with indomethacin in rats

1997 ◽  
Vol 273 (2) ◽  
pp. G355-G364 ◽  
Author(s):  
T. Yamada ◽  
M. Hoshino ◽  
T. Hayakawa ◽  
H. Ohhara ◽  
H. Yamada ◽  
...  
Keyword(s):  
Intestinal Inflammation ◽  
Acid Output ◽  
Blood Chemistry ◽  
Bile Secretion ◽  
Myeloperoxidase Activity ◽  
Hydrophobicity Index ◽  
Subcutaneous Injections ◽  
Elimination Constant ◽  
Hyodeoxycholic Acid ◽  
Inflammatory Action

We investigated the effects of dietary diosgenin (Dio), a plant-derived sapogenin, on indomethacin (Indo)-induced intestinal inflammation and alterations in bile secretion in rats. In anesthetized rats, bile secretion, intestinal inflammation, and blood chemistry were assessed 3 days after two subcutaneous injections of Indo given 24 h apart. Dio (> 80 mg.kg-1.day-1) pretreatment significantly inhibited weight and food intake decreases and intestinal inflammation. This protective effect was confirmed by examination of gross and histological findings and intestinal myeloperoxidase activity. Dio significantly increased biliary cholesterol (Chol) output and prevented the decreases in bile flow, bile acid output, and biliary alpha-muricholic acid and the increases in biliary hyodeoxycholic acid, deoxycholic acid, and hydrophobicity index of bile. Significantly more biliary Chol and phospholipids were present in macromolecules separate from bile acids and Indo in Dio-treated rats. Dio significantly increased the elimination constant of Indo and reduced plasma Indo levels at 3 and 12 h but did not influence biliary secretion of Indo for 3.5 h after injection. Although Dio dose-dependently attenuated subacute intestinal inflammation and normalized bile secretion in this model, it may also compromise the anti-inflammatory action of indo.

Taurochenodeoxycholic acid ameliorates and ursodeoxycholic acid exacerbates small intestinal inflammation

1997 ◽  
Vol 272 (5) ◽  
pp. G1249-G1257 ◽  
Author(s):  
A. Uchida ◽  
T. Yamada ◽  
T. Hayakawa ◽  
M. Hoshino
Keyword(s):  
Bile Acid ◽  
Food Intake ◽  
Ursodeoxycholic Acid ◽  
Bile Acids ◽  
Intestinal Inflammation ◽  
Myeloperoxidase Activity ◽  
Hydrophobicity Index ◽  
Inflammatory Parameters ◽  
Intestinal Length ◽  
Small Intestinal

Intraluminal bacteria, food intake, and bile play important roles in indomethacin-induced small intestinal inflammation in rats. Tauroursodeoxycholic acid (TUDCA) and ursodeoxycholic acid (UDCA) inhibit hydrophobic bile acid-induced damage in various types of cells. We investigated the effects of these bile acids along with the possible influence of other bile acids on this model of inflammation. Clinical and intestinal inflammatory parameters and bile secretion were assessed after 7-day dietary bile acid pretreatments and subsequent indomethacin injections. UDCA significantly enhanced indomethacin-associated reductions in food intake and body weight, increases in gross inflammatory scores and myeloperoxidase activity, and the shortening of small intestinal length. Taurochenodeoxycholic acid (TCDCA) significantly normalized the clinical inflammatory parameters, prevented indomethacin-induced increases in the biliary contents of secondary bile acids and hydrophobicity index, and tended to attenuate the intestinal inflammation. Although elevated biliary levels of muricholic acids and a decreased hydrophobicity index were evident before indomethacin injection in the TCDCA case, these alterations could not explain the TCDCA-mediated protection. Dietary TCDCA attenuates whereas UDCA exacerbates intestinal inflammation in this model. Alterations in the bile composition (increases in UDCA and chenodeoxycholic acid) may explain the observed modification effects.

Bile secretion in rats with indomethacin-induced intestinal inflammation

1996 ◽  
Vol 270 (5) ◽  
pp. G804-G812 ◽  
Author(s):  
T. Yamada ◽  
M. Hoshino ◽  
T. Hayakawa ◽  
Y. Kamiya ◽  
H. Ohhara ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Salt ◽  
Bile Flow ◽  
Intestinal Inflammation ◽  
Acid Output ◽  
Bile Secretion ◽  
Pool Size ◽  
Secretory Function ◽  
Indomethacin Treatment

The objective of this study was to characterize the bile secretion, including the composition of biliary bile acids, bile salt pool size, and transcytotic vesicle transport, in a rat model of subacute intestinal inflammation induced by indomethacin. Indomethacin treatment significantly decreased bile acid-independent bile flow and biliary secretion of bile acid and cholesterol, while increasing biliary phospholipid output in vivo. Although indomethacin treatment did not change the bile salt pool size in vivo, alpha- and beta-muricholic acids were significantly deceased and hyodeoxycholic and deoxycholic acids were increased in bile. Bile flow and the transport maximum of taurocholate did not decrease, and biliary horseradish peroxidase output was significantly enhanced in isolated perfused livers from indomethacin-treated rats. Endotoxin in the portal blood was significantly increased in rats treated with indomethacin. Clindamycin slightly reduced intestinal inflammation but significantly prevented decreases in bile flow, bile acid output, and transport maximum of taurocholate. We conclude that, although biliary secretory function was apparently decreased in vivo, that of hepatocyte function was maintained in this model.

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.

scholarly journals Chronic colitis-induced visceral pain is associated with increased anxiety during quiescent phase

2019 ◽  
Vol 316 (6) ◽  
pp. G692-G700 ◽  
Author(s):  
Emmeline Salameh ◽  
Mathieu Meleine ◽  
Guillaume Gourcerol ◽  
Jean-Claude do Rego ◽  
Jean-Luc do Rego ◽  
...  
Keyword(s):  
Intestinal Inflammation ◽  
Visceral Pain ◽  
Myeloperoxidase Activity ◽  
Therapeutic Approaches ◽  
Chronic Colitis ◽  
Functional Symptoms ◽  
Tnf Α ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Novel Therapeutic

Inflammatory bowel diseases (IBD) are characterized by repetition of flares and remission periods leading to chronic postinflammatory sequelae. Among postinflammatory sequelae, one-third of patients with IBD are suffering from functional symptoms or psychological comorbidities that persist during remission. The aim of our study was to assess functional and behavioral sequelae of chronic colitis in rats with quiescent intestinal inflammation. Chronic colitis was induced by a weekly intrarectal injection of increasing concentrations of trinitrobenzene sulfonic acid (TNBS) for 3 wk (15–45 mg of TNBS) in 30 rats, whereas the control rats ( n = 24) received the vehicle. At 50 days post-TNBS, visceral sensitivity was assessed by visceromotor response to colorectal distension, and transient receptor potential vanilloid type 1 (TRPV1) expression was also quantified in the colon and dorsal root ganglia. Barrier function and inflammatory response were assessed by studying intestinal permeability, tight junction protein, myeloperoxidase activity, histological score, and cytokine production (IL-6, IL-10, and TNF-α). Anxiety behavioral tests were performed from 50 to 64 days after the last TNBS injection. Chronic TNBS induced 1) a visceral hypersensitivity ( P = 0.03), 2) an increased colon weight-to-length ratio ( P = 0.01), 3) higher inflammatory and fibrosis scores ( P = 0.0390 and P = 0.0016, respectively), and 4) a higher colonic IL-6 and IL-10 production ( P = 0.008 and P = 0.005, respectively) compared with control rats. Intestinal permeability, colonic production of TNF-α, myeloperoxidase activity, and TRPV1 expression did not differ among groups. Chronic TNBS increased anxiety-related behavior in the open-field test and in the acoustic stress test. In conclusion, chronic colitis induced functional sequelae such as visceral hypersensitivity and increased anxiety with a low-grade intestinal inflammation. Development of a representative animal model will allow defining novel therapeutic approaches to achieve a better management of IBD-related sequelae.NEW & NOTEWORTHY Patients with inflammatory bowel diseases have impaired quality of life. Therapeutic progress to control mucosal inflammation provides us an opportunity to develop novel approaches to understand mechanisms behind postinflammatory sequelae. We used a chronic colitis model to study long-term sequelae on visceral pain, gut barrier function, and psychological impact. Chronic colitis induced functional symptoms and increased anxiety in the remission period. It might define novel therapeutic approaches to achieve a better inflammatory bowel disease-related sequelae management.

scholarly journals Deletion of neutral endopeptidase exacerbates intestinal inflammation induced by Clostridium difficiletoxin A

2001 ◽  
Vol 281 (2) ◽  
pp. G544-G551 ◽  
Author(s):  
Kimberly S. Kirkwood ◽  
Nigel W. Bunnett ◽  
John Maa ◽  
Ignazio Castagliolo ◽  
Bao Liu ◽  
...  
Keyword(s):  
Acute Inflammation ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Fluid Secretion ◽  
Neutral Endopeptidase ◽  
Myeloperoxidase Activity ◽  
Wild Type ◽  
Neutrophil Accumulation ◽  
Genetic Deletion ◽  
Neurokinin 1

Toxin A (TxA) of Clostridium difficile induces acute inflammation of the intestine initiated by release of substance P (SP) and activation of the neurokinin-1 receptor. However, the mechanisms that terminate this response are unknown. We determined whether the SP-degrading enzyme neutral endopeptidase (NEP, EC 3.4.24.11 ) terminates TxA-induced enteritis. We used both genetic deletion and pharmacological inhibition of NEP to test this hypothesis. In wild-type mice, instillation of TxA (0.5–5 μg) into ileal loops for 3 h dose dependently increased ileal fluid secretion, stimulated granulocyte transmigration determined by myeloperoxidase activity, and caused histological damage characterized by depletion of enterocytes, edema, and neutrophil accumulation. Deletion of NEP reduced the threshold secretory and inflammatory dose of TxA and exacerbated the inflammatory responses by more than twofold. This exacerbated inflammation was prevented by pretreatment with recombinant NEP. Conversely, pretreatment of wild-type mice with the NEP inhibitor phosphoramidon exacerbated enteritis. Thus NEP terminates enteritis induced by C. difficile TxA, underlying the importance of SP degradation in limiting neurogenic inflammation.

scholarly journals Comparative studies on bile flow and biliary lipid excretion after bile-acid loading in normal and partially hepatectomized rats

1995 ◽  
Vol 305 (2) ◽  
pp. 367-371 ◽  
Author(s):  
M Hoshino ◽  
A Hirano ◽  
T Hayakawa ◽  
Y Kamiya ◽  
T Ohiwa ◽  
...  
Keyword(s):  
Bile Acid ◽  
Rat Liver ◽  
Bile Flow ◽  
Acid Output ◽  
Bile Secretion ◽  
Biliary Lipid ◽  
Isolated Perfusion ◽  
Acid Loading ◽  
Second Peak

This study was performed to investigate sequential changes in bile secretion and biliary lipids after taurocholic acid (TCA) loading of regenerating rat liver. TCA was administered intravenously at stepwise-increasing doses to groups of non-operated control and partially hepatectomized rats, 24, 72 and 168 h after surgery. Bile flow, bile-acid output (BAO) and phospholipid output (PLO) (expressed per gram of liver) in partially hepatectomized rats increased more than in the controls. Using an isolated perfusion rat-liver system, TCA infusion was also carried out on groups of non-operated control and hepatectomized rats 72 h after operation. Again bile flow, BAO and PLO (expressed per gram of liver) were significantly higher in the partial hepatectomy case, mirroring the results obtained in vivo. When horseradish peroxidase (HRP) was pulse-loaded in isolated perfusion preparations, the second peak of biliary HRP secretion in hepatectomized rats was significantly higher than in controls. We conclude that increased bile-acid flow in partially hepatectomized rats is dependent upon acceleration of vesicular transport accompanying or following proliferation in regenerating livers.

Functional alterations in jejunal myenteric neurons during inflammation in nematode-infected guinea pigs

1998 ◽  
Vol 275 (5) ◽  
pp. G922-G935 ◽  
Author(s):  
Jeffrey M. Palmer ◽  
Margaret Wong-Riley ◽  
Keith A. Sharkey
Keyword(s):  
Metabolic Activity ◽  
Guinea Pigs ◽  
Intestinal Inflammation ◽  
Ganglion Cells ◽  
Trichinella Spiralis ◽  
Input Resistance ◽  
Excitatory Postsynaptic Potential ◽  
Myeloperoxidase Activity ◽  
Double Labeling ◽  
Myenteric Neurons

Intracellular recordings of jejunal myenteric neurons with an afterspike hyperpolarization (AH) from Trichinella spiralis-infected animals showed enhanced excitability on days 3, 6, and 10postinfection (PI) compared with uninfected animals. Lower membrane potential, increased membrane input resistance, decreased threshold for action potential discharge, decreased AH amplitude and duration, and increased fast excitatory postsynaptic potential amplitude and duration were characteristic of neuronal recordings from infected animals. Concurrent with electrophysiological changes during T. spiralis infection, increased cytochrome oxidase activity, a marker of neuronal metabolic activity, and the expression of nuclear c-Fos immunoreactivity, an indicator of transcriptional-translational activity, were also observed in myenteric ganglion cells. Double-labeling for calbindin-immunoreactive myenteric neurons revealed that ∼50% of these neurons also expressed increased c-Fos immunoreactivity during T. spiralis infection. Myeloperoxidase activity was significantly higher in the jejunum of T. spiralis-infected guinea pigs on days 3, 6, and 10 PI vs. uninfected counterparts. The expression of c-Fos in calbindin-immunoreactive neurons together with enhanced neuronal electrical and metabolic activity during nematode-induced intestinal inflammation suggests the onset of excitation-transcription coupled changes in enteric neural microcircuits.

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 Vaccination Against Poly-N-Acetylglucosamine Decreases Neutrophil Activation and Gvhd While Maintaining Microbial Diversity

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3209-3209
Author(s):  
Eileen Haring ◽  
Jan Hülsdünker ◽  
Oliver Thomas ◽  
Susanne Unger ◽  
Nicolás Núñez ◽  
...  
Keyword(s):  
Microbial Diversity ◽  
Intestinal Inflammation ◽  
Passive Immunization ◽  
Neutrophil Activation ◽  
Neutrophil Granulocytes ◽  
Myeloperoxidase Activity ◽  
Sequencing Analysis ◽  
Antibody Treatment ◽  
Microbial Invasion ◽  
Equity Ownership

Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative therapy for different malignant and non-malignant hematologic diseases. Major life-threatening complications after allo-HCT are acute graft-versus-host disease (aGVHD) and severe infections. The incidence of GVHD after allo-HCT remains high, despite prophylactic immunosuppressive medication. According to the CIBMTR database, 60% of patients undergoing allo-HCT develop at least grade II-IV aGVHD. Microbial invasion into the intestinal mucosa after allo-HCT triggers the activation of neutrophil granulocytes (neutrophils) and requires antibiotic treatment to prevent sepsis. However, antibiotics lead to a loss of microbial diversity, which is connected to a higher incidence of aGVHD. Anti-microbial therapies which eliminate invading bacteria and diminish neutrophil-mediated damage without reducing the diversity of the microbiota are therefore highly desirable. A potential solution for this could be the use of anti-microbial antibodies that target and mark invading pathogens resulting in their elimination by innate immune cells. Therefore we investigated the potency of both active and passive immunization against the conserved microbial surface polysaccharide Poly-N-acetylglucosamine (PNAG) which is expressed on various pathogens in a murine aGVHD model. We could detect reduced aGVHD related mortality in mice which underwent treatment with an antibody against PNAG (anti-PNAG) or were actively immunized against PNAG. Sequencing analysis of the microbiota before and after allo-HCT showed that anti-PNAG treatment did not have any effect luminal microbial diversity. Mechanistically, we could show that anti-PNAG antibody treatment caused more abundant neutrophil recruitment to the intestinal submucosa. This supports the concept that neutrophils are able to effectively eliminate any opsonized bacteria in this tissue, leading to reduced local inflammation. In agreement with this we observed lower intestinal inflammation and reduced myeloperoxidase activity as well as proliferation of neutrophils in the small intestine of mice treated with anti-PNAG antibody. We demonstrate the potency of targeting PNAG as a novel antimicrobial treatment option in aGVHD by reducing uncontrolled neutrophil activation and thereby interfering with aGVHD without affecting commensal intestinal microbial diversity. Anti-PNAG-antibodies enhance anti-microbial immunity, while reducing the activation of neutrophil-mediated downstream immunopathology which is a novel approach to reduce the severity of GVHD. This could be translated into a clinical application given the modest toxicity profile of vaccination and the availability of fully human anti-PNAG antibodies, both of which have been tested in phase 1 trials in humans (ClinicalTrials.gov Identifier: NCT02853617). Disclosures Cywes-Bentley: OneBiopharma, Inc.: Honoraria. Koenecke:Novartis: Other: none. Pier:OneBiopharma, Inc.: Equity Ownership, Honoraria; Alopexx Vaccine, LLC: Equity Ownership, Honoraria.

scholarly journals NITRIC OXIDE INTERFERES WITH HYPOXIA SIGNALING DURING COLONIC INFLAMMATION

2014 ◽  
Vol 51 (4) ◽  
pp. 302-308 ◽  
Author(s):  
Cintia Rabelo e Paiva CARIA ◽  
Camila Henrique MOSCATO ◽  
Renata Bortolin Guerra TOMÉ ◽  
José PEDRAZZOLI Jr ◽  
Marcelo Lima RIBEIRO ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Intestinal Inflammation ◽  
Repeated Administration ◽  
Myeloperoxidase Activity ◽  
Ester Hydrochloride ◽  
Methyl Ester Hydrochloride ◽  
Colonic Inflammation ◽  
Endothelial Growth Factor ◽  
Hypoxia Signaling

Context Intestinal inflammation can induce a local reduction in oxygen levels that triggers an adaptive response centered on the expression of hypoxia-inducible factors (HIFs). Nitric oxide, a well-described inflammatory mediator, may interfere with hypoxia signaling. Objectives We aimed to evaluate the role of nitric oxide in hypoxia signaling during colonic inflammation. Methods Colitis was induced by single (acute) or repeated (reactivated colitis) trinitrobenzenosulfonic acid administration in rats. In addition, one group of rats with reactivated colitis was also treated with Nw-Nitro-L-arginine methyl ester hydrochloride to block nitric oxide synthase. Colitis was assessed by macroscopic score and myeloperoxidase activity in the colon samples. Hypoxia was determined using the oxygen-dependent probe, pimonidazole. The expression of HIF-1α and HIF-induced factors (vascular endothelial growth factor - VEGF and apelin) was assessed using Western blotting. Results The single or repeated administration of trinitrobenzenosulfonic acid to rats induced colitis which was characterized by a high macroscopic score and myeloperoxidase activity. Hypoxia was observed with both protocols. During acute colitis, HIF-1α expression was not increased, but VEGF and apelin were increased. HIF-1α expression was inhibited during reactivated colitis, and VEGF and apelin were not increased. Nw-Nitro-L-arginine methyl ester hydrochloride blockade during reactivated colitis restored HIF-1α, VEGF and apelin expression. Conclusions Nitric oxide could interfere with hypoxia signaling during reactivated colitis inflammation modifying the expression of proteins regulated by HIF-1α.

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