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Results for “Intestinal Barrier Function”

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At least 235 records · Page 13Linked to original sources

PubMed1997

Bidirectional small intestinal permeability changes to different-sized molecules after HCl-induced injury in the rat.

A rat model was developed to assess bidirectional passage of macromolecules and low-molecular-weight markers across the intestinal barrier in intact and injured mucosa. Isolated in situ loops of distal small intestine were luminally perfused for 30 min with saline as control or HCI (pH 2.0) to induce an acute injury. The lumen-to-blood passage was followed during perfusion with bovine serum albumin, [14C]mannitol, and sodium fluorescein. Intravenously administered sodium fluorescein and endogenous serum albumin were used as blood-to-lumen markers. Acid exposure resulted in severe injury of the villi tips, with significantly increased lumen-to-blood passage of all markers compared with that of intact mucosa. Moreover, blood-to-lumen passage of rat serum albumin increased after the injury, while that of sodium fluorescein did not. The acid induced injury impaired the intestinal barrier function with an increased marker passage, where the macromolecules were more sensitive markers of the altered barrier function than low-molecular-weight markers.

Acute Disease↗

PubMed2002

Mechanism of action of EPEC type III effector molecules.

Enteropathogenic E. coli (EPEC) is a prototypic member of the family of related 'attaching and effacing (A/E)' pathogens that induce diarrhoeal disease, especially to the young that can be fatal, of a wide range of mammalian species. Disease is correlated with the loss of absorptive gut epithelial microvilli and the reorganisation of host cytoskeletal proteins into pedestal-like structures beneath the adherent bacteria. These phenotypes are dependent on a pathogenicity island (LEE; Locus of Enterocyte Effacement) encoding a type III secretion system, secreted proteins, chaperone molecules, regulatory proteins and the bacterial outer membrane protein intimin. The type III secretion apparatus directs the transfer of specific proteins across the bacterial envelope, with a subset (EPEC secreted proteins - EspA, EspB and EspD) functioning to transfer effector proteins into host cells. These effector molecules subvert cellular processes that undoubtedly benefit the pathogen and contribute to disease. Three LEE-encoded EPEC effector molecules have so far been identified with one, Tir (Translocated intimin receptor), being transferred into host cells where it is modified by host kinases and becomes inserted into the plasma membrane to orchestrate cytoskeletal rearrangements linked to disease. This activity is dependent on its interaction with intimin and on tyrosine phosphorylation, with Tir-intimin interaction essential for virulence. A second effector Map, Mitochondrial-associated protein, is targeted to mitochondria where it has membrane-potential disrupting activity. The third, EspF disrupts intestinal barrier function and can induce host cell death by unknown mechanisms. Recent data relating to the mechanism by which Tir and Map function within host cells is discussed.

Animals↗

PubMed2004

[Effect of mold fungus spore consumption with food on systemic anaphylaxis in rats].

An influence was studied in experiment of intragastrically administrated milk cream contaminated with mould fungi spores on systemic anaphylactic reaction gravity in Wistar albino rats sensitized with egg albumin (EA). During 28 days sensitized rats intragastrically received cream containing 10(3) or 10(6) colony forming units of 5 fungal species in one cm3. After being challenged rats developed mild anaphylactic shock followed by elevation of small intestinal permeability for macromolecular tracer polyethylene glycol 4000. An increase of small intestinal permeability was also noticed in unsensitized rats that were fed with cream contaminated with 10(6) spores per cm3. Unexpectedly these effects were not additive: the intestinal permeability in sensitized rats decreased at maximal level of contamination. This may be explained by strengthening of gastrointestinal motility in these animals. Significant elevation of antibody production against EA was revealed in sensitized rats that received cream contaminated by spores at high level. The data obtained signify that milk products fungal contamination that could not be revealed by sense may nevertheless have negative impact on intestinal barrier function and sensitization.

Anaphylaxis↗

PubMed1980

Intestinal barrier to large particulates in mice.

Intestinal barrier function in mice was assessed after acute or chronic oral administration of 15.8- and 5.7-micron synthetic spherical particles. The results failed to confirm previous reports that ingested particles rapidly appear in blood. Furthermore, 15.8-micron particles did not accumulate in intestinal Peyer's patches, mesenteric lymph nodes, or other organs of the reticuloendothelial system, even after the maximum dosage of 8 X 10(6) particles per day for 60 d. However, the 5.7-micron particles were demonstrated in Peyer's patches, mesenteric lymph nodes, and lungs after the maximum dosage of 4.5 X 10(8) particles per day for 60 d. At 77 d after the termination of ingestion, 5.7-micron particles were still present in these tissues. The 5.7-micron particles were not found in spleen; retention in liver was equivocal. The site of uptake of particles capable of penetrating the intestinal mucosa appears to be the Peyer's patches. It is suggested that most absorbed particles are sequestered in Peyer's patch macrophages. Particles that escape sequestration are transported by lymph rather than by portal blood. The findings indicate that hazards associated with intestinal uptake of large (> 5 micron) particulates exist, but that the frequency of such penetration is still unclear.

Animals↗

PubMed1999

Intestinal permeability in liver cirrhosis: relationship with severe septic complications.

OBJECTIVES: Patients with liver cirrhosis are at high risk of severe septic complications such as spontaneous bacterial peritonitis (SBP) and bacteraemia. The aims of this study were to assess intestinal permeability in patients with liver cirrhosis and to search for a relationship between an impaired intestinal permeability and the occurrence of severe septic complications. METHODS: Intestinal permeability was assessed in a group of 80 cirrhotic patients (Child A, n = 13; Child B, n = 26; Child C, n = 41) and 28 healthy control subjects. A severe septic complication (bacteraemia and/or SBP) occurred in 16 patients, within 10 days before (n = 8 cases) or after (n = 8 cases) the test was performed. Lactulose (LAC) 10 g was given orally together with mannitol (MAN) 5 g, and urinary excretion rates were determined. RESULTS: Urinary mannitol excretion (MAN%) was lower while the LAC/MAN ratio was higher in patients than in control subjects (P < 0.001); these abnormalities were more marked in Child C patients (Child C patients vs control subjects: MAN%, 8.20 +/- 0.79 vs 14.59 +/- 0.58, P < 0.001; LAC/MAN, 0.066 +/- 0.026 vs 0.017 +/- 0.001, P < 0.02). When compared with non-infected patients, septic patients had a lower MAN% and an increased LAC/ MAN ratio (5.45 +/- 1.12 vs 9.83 +/- 0.87, P < 0.02; 0.130 +/- 0.063 vs 0.029 +/- 0.005, P < 0.02). CONCLUSION: Although the main mechanism involved in the decrease in MAN% is likely a reduction in area of the intestinal absorptive surface, these results argue in favour of an increased intestinal permeability in liver cirrhosis, especially in patients with severe infectious complications. The impairment of intestinal function barrier may contribute to severe septic complications in these patients.

Bacteremia↗

PubMed2001

Zinc supplementation tightens "leaky gut" in Crohn's disease.

OBJECTIVES: Small intestinal permeability is often increased in patients with Crohn's disease and may be pathogenic for clinical relapses. No effective prophylactic treatment is available for these patients. The aim of this study was to ascertain whether zinc supplementation may improve intestinal permeability. METHODS: We studied 12 patients with quiescent Crohn's disease who had been in remission for at least 3 months and had increased intestinal permeability on two separate occasions within the last 2 months. Patients received oral zinc sulfate supplements (110 mg three times a day) for 8 weeks and were followed-up for 12 months thereafter to monitor relapses. RESULTS: We found that the lactulose/mannitol ratio was significantly higher before supplementation than after (0.041 +/- 0.003 versus 0.026 +/- 0.005). During follow-up, 10 patients had normal intestinal permeability and did not relapse; of the remaining two who had increased intestinal permeability, one relapsed. CONCLUSIONS: Our findings show that zinc supplementation can resolve permeability alterations in patients with Crohn's disease in remission. Improving intestinal barrier function may contribute to reduce the risk of relapse in Crohn's disease.

Adult↗

PubMed2001

Hypoxia-inducible factor 1-dependent induction of intestinal trefoil factor protects barrier function during hypoxia.

Mucosal organs such as the intestine are supported by a rich and complex underlying vasculature. For this reason, the intestine, and particularly barrier-protective epithelial cells, are susceptible to damage related to diminished blood flow and concomitant tissue hypoxia. We sought to identify compensatory mechanisms that protect epithelial barrier during episodes of intestinal hypoxia. Initial studies examining T84 colonic epithelial cells revealed that barrier function is uniquely resistant to changes elicited by hypoxia. A search for intestinal-specific, barrier-protective factors revealed that the human intestinal trefoil factor (ITF) gene promoter bears a previously unappreciated binding site for hypoxia-inducible factor (HIF)-1. Hypoxia resulted in parallel induction of ITF mRNA and protein. Electrophoretic mobility shift assay analysis using ITF-specific, HIF-1 consensus motifs resulted in a hypoxia-inducible DNA binding activity, and loading cells with antisense oligonucleotides directed against the alpha chain of HIF-1 resulted in a loss of ITF hypoxia inducibility. Moreover, addition of anti-ITF antibody resulted in a loss of barrier function in epithelial cells exposed to hypoxia, and the addition of recombinant human ITF to vascular endothelial cells partially protected endothelial cells from hypoxia-elicited barrier disruption. Extensions of these studies in vivo revealed prominent hypoxia-elicited increases in intestinal permeability in ITF null mice. HIF-1-dependent induction of ITF may provide an adaptive link for maintenance of barrier function during hypoxia.

Animals↗

PubMed1994

Early morphological changes in Crohn's disease. Transmission electron-microscopic findings and their interpretation: an overview.

Recent ultrastructural investigations revealed early epithelial lesions in Crohn's disease, while a specific morphological pattern was not identifiable. An increase in plasma cells, lymphocytes, macrophages, mast cells, eosinophilic and neutrophilic granulocytes, as well as focal edema and inflammation of tissue structures was seen in the lamina propria, submucosa and deeper layers. The results are consistent with the frequent discussion about a pathogenetically significant defect of the mucosal 'barrier function', which consists of mechanical, cellular, humoral, immunological and nonimmunological mechanisms, including different histotopographically defined lines of defense of the epithelium and lamina propria. An intact epithelial layer plays an important role as the first line of defense. It is evident that components of the epithelial barrier (absorptive cells, goblet cells, Paneth cells, M cells) show ultrastructural signs of alteration or injury, while the primary agent or event remains unknown. Another pathomechanism would be a preexisting defect in intestinal 'barrier function'. Such a defect would result in an increased uptake of, or an inadequate immune reaction to, ubiquitously occurring antigens/agents (with genetic predisposition). However, no primary defect of epithelial or inflammatory cells has been definitely identified so far. Direct toxic damage of tissue secondarily introducing the inflammatory changes is also possible. Although the morphological alterations in Crohn's disease are not yet clearly understood and exactly interpreted, transmission electron microscopy has been helpful in defining early lesions and has led to further knowledge about the pathogenesis of this disease.

Crohn Disease↗

PubMed2001

Subchronic mild noise stress increases HRP permeability in rat small intestine in vitro.

Recently we reported an increased trans- and paracellular protein permeability in rat small intestine after acute cold restraint stress. In the present study, we applied randomized 95- or 105-dB white noise pulses during 45 min/h, 12 h/day, duration 8 days, as a milder, but more chronic stressor to male rats. At 8 days before the noise experiments, 50% of the animals were cannulated in the vena cava for blood sampling during the experimental period. The other 50% of the animals were sacrificed at Day 9, segments of ileum were mounted in Ussing chambers and perfused at 37 degrees C. Horseradish peroxidase (HRP) was added mucosally, serosal appearance was detected enzymatically and tissues were fixed for electron microscopy. In the animals exposed to 95-dB noise, plasma corticosterone levels were enhanced twofold compared to controls, and ileal HRP flux was enhanced twofold. Electron micrographs of tissue from stressed or control animals showed no detectable paracellular staining of HRP. Quantification of HRP-containing endosomes in enterocytes revealed a twofold increase in endosome number in the animals exposed to 95-db noise indicating that the increased HRP permeability was primarily due to increased endocytosis. In contrast to the animals exposed to 95-dB noise, rats exposed to 105-dB noise showed no increase in corticosterone levels and ileal HRP fluxes were not significantly different from controls. We conclude that mild subchronic noise stress may cause a decrease in intestinal barrier function by increased transcytosis of luminal antigens.

Animals↗

PubMed1991

Intestinal permeability in patients with yersinia triggered reactive arthritis.

The passive intestinal permeability of patients with yersinia triggered reactive arthritis was studied using different sized polyethylene glycols (PEGs) contained in a mixture of PEG 400 and PEG 1000. The investigation was carried out at least one year after the onset of yersinia infection, and patients had neither acute gastrointestinal nor joint symptoms. The control groups included patients with uncomplicated yersiniosis as well as healthy subjects who were either HLA-B27 positive or negative. An altered intestinal barrier function to PEG molecules was detected in patients with a history of yersinia infection compared with healthy controls. No significant differences in the permeability were found between patients with or without reactive arthritis, nor was there any association of increased permeability with HLA-B27. The passive permeability of the intestinal mucosa to the larger molecules was increased for an unexpectedly long time after the acute yersinia infection, probably contributing to the perpetuation of joint symptoms in subjects susceptible to a chronic joint disease.

Adult↗

PubMedDate not supplied

Interrelation of intracellular proteases with total parenteral nutrition-induced gut mucosal atrophy and increase of mucosal macromolecular transmission in rats.

Total parenteral nutrition (TPN) is known to induce mucosal atrophy and to increase macromolecular transmission of the small intestine. The potential participation of various proteases in that process was investigated. Male Wistar rats were randomly divided into two groups: the TPN group (n = 11) received a standard TPN (250 kcal/kg per day, 1.78 g nitrogen/kg per day) and the FED group (n = 10) received a standard rat food for 1 week. This was followed by an examination of gut macromolecular transmission of fluorescein isothiocyanate dextran 70,000 (FITC-dextran) after intragastric injection and of the activities of gut mucosal cathepsins B, H, and L and of proteasome. Mucosal wet weight and protein content decreased significantly by TPN for 1 week. In both groups, the activities of all proteases in the ileum were significantly greater than in the jejunum. In the TPN group, cathepsin L and H activities in the ileum, and cathepsin B activity in both the jejunum and the ileum, were greater than those in the FED group. The portal concentration of FITC-dextran was higher than arterial and venous concentrations in the both groups. In the TPN group, the portal FITC-dextran concentration increased significantly compared with the FED group. In conclusion, active proteolysis is not associated with TPN-induced mucosal atrophy. Cathepsins activities in the ileum increase as a result of TPN. Interrelationship is implicated between increase of lysosomal protease activity and the deterioration of the intestinal barrier function, which permits macromolecular transmission.

Animals↗

PubMed1996

Trauma, shock, and gut translocation.

This article reviews the scientific and clinical evidence that supports trauma and shock as potential etiologies for translocation of intestinal microorganisms and their by-products. The potential for loss of intestinal barrier function to cause the eventual septic deaths observed in such patients, as well as possible mechanisms for preventing and treating this entity is also discussed.

Animals↗

PubMed2004

Pretreatment with high-fat enteral nutrition reduces endotoxin and tumor necrosis factor-alpha and preserves gut barrier function early after hemorrhagic shock.

Gram-negative sepsis is a potentially fatal clinical syndrome characterized by a proinflammatory response (tumor necrosis factor-alpha) to bacterial (endo)toxins and gut barrier function loss. Recently, we found that high-fat enteral nutrition protects against late bacterial translocation in a model of hemorrhagic shock in rats. However, the basis for this protection is unknown. We hypothesized that the observed protection is the result of an early inhibition of endotoxin and the subsequent inflammatory response resulting in a preserved gut barrier function. Sprague-Dawley rats were divided into a group that was starved overnight (HS-S), fed with a low-fat enteral diet (HS-LF) or fed wih a high-fat enteral diet (HS-HF), and subsequently subjected to a nonlethal hemorrhagic shock. Ninety minutes after hemorrhage, arterial endotoxin significantly decreased in HS-HF rats (4.0 +/- 0.6 pg/mL) compared with HS-LF rats (10.7 +/- 0.9 pg/mL, P = 0.002) and HS-S rats (15.2 +/- 2.2 pg/mL P = 0.001). Interestingly, arterial tumor necrosis factor-alpha was also decreased in HS-HF rats (17.9 +/- 10.4 pg/mL) compared with HS-LF (83.5 +/- 16.7 pg/mL, P < 0.01) and HS-S rats (180.9 +/- 67.9 pg/mL, P < 0.02). Loss of tight junction structure (ZO-1) observed in ileum and colon of control hemorrhagic shock rats was prevented in HS-HF rats. In parallel, intestinal barrier function was preserved in HS-HF rats, evidenced by a reduced permeability to horseradish peroxidase (P < 0.05), less bacterial invasion, and a 10-fold reduction of bacterial translocation early after hemorrhagic shock. This report describes a new strategy to nutritionally prevent endotoxemia, the subsequent inflammatory response and gut barrier failure following hemorrhagic shock. High-fat enteral nutrition requires further evaluation as an intervention to prevent a potentially fatal systemic inflammatory response in patients at risk for sepsis.

Animal Feed↗

PubMed2006

The effect of insulin-like growth factor-I on hepatocyte apoptosis after bile duct ligation in rat.

Obstructive jaundice may promote bacterial overgrowth and altered intestinal barrier function, with resultant increased translocation of endotoxin to the liver, amd thus may potentiate the phenomenon of hepatocyte apoptosis. Exogenous administration of insulin-like growth factor-I (IGF-I) has been shown to enhance mucosal adaptation after small bowel resection in rats and also to accelerate repair of small intestinal mucosa after damage by the chemotherapy drug methotrexate. The aim of the current study was to determine the effect of exogenous IGF-I administration on hepatocyte apoptosis after bile duct ligation in rat. Male Sprague-Dawley rats weighing 250-300 g were randomized to three groups (n=6 in each group). Group 1 (control; C) underwent sham operation and was simultaneously treated with the same amount of normal saline. Group 2 (obstructive jaundice; OB) underwent common bile duct ligation without other manipulation. Group 3 (obstructive jaundice with IGF-I; OBIGF-I) underwent common bile duct ligation and simultaneous treatment with recombinant human IGF-I (a total dose of 1 mg in each rat, divided into six administrations; about 1 mg/kg/day). After 3 days, liver tissue was harvested and immediately snap-frozen in liquid nitrogen for histopathologic analysis and apoptosis measurements. Compared with the sham operation group (C), increased hepatocyte apoptosis (P < 0.001) and ductular proliferation (P < 0.001) occurred after common bile duct ligation (OB). After administration of IGF-I (OBIFG-I), the increased hepatocyte apoptosis and ductular proliferation after common bile duct ligation (OB) were significantly diminished (P < 0.001 and P < 0.001, respectively). There was no significant difference in hepatocyte apoptosis (P=0.925) or ductular proliferation (P=0.385) between the sham control group (C) and the OBIGF-I group. Increased hepatocyte apoptosis (P < 0.001) and ductular proliferation (P < 0.001) occurred after common bile duct ligation (OB). After administration of IGF-I (OBIFG-I), the increased hepatocyte apoptosis and ductular proliferation after common bile duct ligation (OB) were significantly diminished (P < 0.001 and P < 0.001, respectively).

Animals↗

PubMed1999

A tungsten supplemented diet attenuates bacterial translocation in chronic portal hypertensive and cholestatic rats: role of xanthine dehydrogenase and xanthine oxidase.

BACKGROUND: Bacterial translocation (BT) plays a major role in the pathophysiological process of spontaneous infections in portal hypertension (PH) and cholestatic jaundice. The major mechanisms promoting BT in experimental animal models are the disruption of the intestinal ecological equilibrium and disruption of the intestinal mucosal barrier. The enzymes xanthine dehydrogenase (XD) and xanthine oxidase (XO) are often implicated as a significant source of oxidants which have a major impact on the impairment of intestinal barrier function. AIM: To investigate the incidence of BT in rats with PH and obstructive jaundice, and to evaluate the impact of XD and XO. METHODS: Animals were subjected to sham laparotomy (SL), PH by calibrated stenosis of the portal vein, and common bile duct ligation (CBDL). They were fed either a standard pellet diet or a tungsten supplemented molybdenum-free diet. Four weeks after the operative procedure, intestinal colonisation and BT to portal vein, vena cava, mesenteric lymph nodes, liver, and spleen were determined. Intestinal XD and XO activity were measured enzymatically and histochemically. RESULTS: Significant (p<0.01) intestinal bacterial overgrowth was present in all PH and CBDL groups compared with the SL group. In normally fed animals after SL, BT occurred in 12%. In PH and after CBDL, the rate of BT increased significantly (p<0.05) to 28% and 54% respectively. In the jejunum of normally fed animals subjected to PH or CBDL, a significant increase in XO was observed (p<0.01). Animals fed a tungsten supplemented diet showed a significant attenuation of BT to 14% in PH and 22% after CBDL (p<0. 05). Tungsten treatment completely suppressed jejunal XD and XO activities. CONCLUSIONS: Significant intestinal bacterial overgrowth, BT, and XD to XO conversion occurred in PH and after CBDL. XD and XO inactivation by a tungsten supplemented molybdenum-free diet significantly reduced the incidence of BT without affecting intestinal bacterial overgrowth. These data strongly support the hypothesis that increased XD to XO conversion may contribute to intestinal barrier failure in PH and after CBDL.

Animals↗

PubMed2000

Polyunsaturated fatty acids reduce non-receptor-mediated transcellular permeation of protein across a model of intestinal epithelium in vitro.

BACKGROUND: Dietary polyunsaturated fatty acids influence the natural history of intestinal inflammatory diseases. Varying the types of long-chain fatty acids that are exposed to cells alters the physicochemical properties of cell membranes. This study aimed to determine whether such variations alter transcellular and paracellular permeability in intestinal epithelium. METHODS: Monolayers of Caco-2 cells, allowed to differentiate by culturing for 7 days following confluence, were used as the model for intestinal epithelium. Paracellular permeability was assessed by measurement of transepithelial resistance, while transcellular permeability was assessed by the transepithelial flux of horseradish peroxidase. RESULTS: Exposure of the cells to 100 micromol/L of palmitic acid, oleic acid, eicosapentaenoic acid, or linoleic acid, was not toxic to cells (measured by leakage of lactate dehydrogenase), and altered cell membrane fatty acid composition (as measured by gas chromatography). Flux of horseradish peroxidase was significantly affected by 24 h fatty acid exposure (P= 0.038, ANOVA), being decreased by 23 +/- 6% (mean +/- SEM) by eicosapentaenoic acid and 25 +/- 3% by linoleic acid. Oleic acid, palmitic acid and butyrate, had no effect. Transepithelial resistance also varied significantly across the treatment groups (P< 0.001) due to a 28 +/- 5% increase induced by butyrate. The long-chain fatty acids had no effect. CONCLUSIONS: Both omega-3 and omega-6 polyunsaturated fatty acids reduce transcellular, non-receptor-mediated permeation of proteins across differentiated Caco2 cell monolayers, without altering paracellular permeability. Alteration of intestinal barrier function should be considered as a possible mechanism of action of dietary polyunsaturated fatty acids.

Butyrates↗

PubMed2005

Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabetic-prone rats.

Increased intestinal permeability has been observed in numerous human autoimmune diseases, including type-1 diabetes (T1D) and its' animal model, the BB-wor diabetic prone rat. We have recently described zonulin, a protein that regulates intercellular tight junctions. The objective of this study was to establish whether zonulin-dependent increased intestinal permeability plays a role in the pathogenesis of T1D. In the BB diabetic-prone rat model of T1D, intestinal intraluminal zonulin levels were elevated 35-fold compared to control BB diabetic-resistant rats. Zonulin up-regulation was coincident with decreased small intestinal transepithelial electrical resistance, and was followed by the production of autoantibodies against pancreatic beta cells, which preceded the onset of clinically evident T1D by approximately 25 days. In those diabetic prone rats that did not progress to diabetes, both intraluminal zonulin and transepithelial electrical resistance were similar to those detected in diabetic-resistant animal controls. Blockade of the zonulin receptor reduced the cumulative incidence of T1D by 70%, despite the persistence of intraluminal zonulin up-regulation. Moreover, treatment responders did not seroconvert to islet cell antibodies. Combined together, these findings suggest that the zonulin-induced loss in small intestinal barrier function is involved in the pathogenesis of T1D in the BB diabetic-prone animal model.

Animals↗

PubMed1986

Effect of non-steroidal anti-inflammatory drugs and prostaglandins on the permeability of the human small intestine.

Intestinal permeability was estimated in healthy subjects after ingestion of aspirin (1.2+1.2 g), ibuprofen (400+400 mg) and indomethacin (75+50 mg) at midnight and an hour before starting a 51chromium labelled ethylenediaminetetraacetate absorption test. Intestinal permeability increased significantly from control levels following each drug and the effect was related to drug potency to inhibit cyclooxygenase. Intestinal permeability increased to a similar extent after oral and rectal administration of indomethacin showing that the effect is systemically mediated. Prostaglandin E2 decreased intestinal permeability significantly but failed to prevent the indomethacin induced increased intestinal permeability. These studies show that non-steroidal anti-inflammatory drugs disrupt the intestinal barrier function in man and suggest that the morphological correlates of the damage may reside at the level of the intercellular junctions.

Adult↗