Changes In Mucosal Permeability Research Articles

Dysbiosis and obesity: implications of the gut microbiota

Introduction: Obesity has been considered a public health crisis, contributing as a risk factor for several important chronic diseases and even death. Considering this fact, it is noteworthy that there is a fundamental relationship between the intestine and health, and this organ is considered by modern medicine as our second brain in the concept of intestinal permeability. Within the evaluation of the food process, effective nutritional absorption can be altered due to imbalances, such as malabsorption, drug-nutrient interaction, changes in mucosal permeability, and, consequently, an imbalance in the gut microbiota. Dysbiosis is characterized by these negative changes that occur in the intestine. In this sense, the present systematic review study sought to answer: What influences can the microbiota composition have on the metabolic syndrome and obesity process? Objective: To elucidate the relationship between the presence of intestinal dysbiosis in the pathogenesis of obesity. Methods: This is a bibliographic review work where the MEDLINE, PubMed, and SciELO databases were consulted using the following descriptors: Human gut microbiota, obesity, dysbiosis. Results and Conclusion: Based on the literature that supports this theme, it was possible to observe that in the obese population there is an increase in bacteria of the genus Firmicutes and a decrease in the genus Bacteriodetes, with the blocking of factors and proteins that regulate the homeostasis of the absorption of lipids and fatty acids being observed thus being able to alter the energy metabolism leading to a greater accumulation of adipose tissue.

Effect of bowel preparation on intestinal permeability and inflammatory response during postoperative ileus in mice

BackgroundPostoperative ileus entails pathophysiological changes in mucosal permeability and an intestinal inflammatory immune response. We hypothesized that preoperative selective decontamination of the digestive tract combined with preoperative mechanical bowel preparation might be advantageous to prevent or reduce permeability changes and immune response in postoperative ileus. MethodsPostoperative ileus was induced in mice by standardized small bowel manipulation. Intervention groups received selective decontamination and/or intestinal lavage with normal saline simulating mechanical bowel preparation before postoperative ileus induction. At 1, 3, and 9 hours after surgery, ileum samples were harvested for measurements of fluorescein (332 Da) permeability, quantification of tumor necrosis factor α-mRNA level, and leukocyte infiltration of the intestinal wall. ResultsMucosal fluorescein permeability increased at 1 hour (8.6 ± 1.1 vs 5.9 ± 0.9 10–6 cm/s; P < .01) and 3 hours (8.5 ± 0.6 vs 6.5 ± 0.2 10–6 cm/s; P < .05) after induction of postoperative ileus. This increase was prevented by mechanical bowel preparation and selective decontamination+mechanical bowel preparation interventions at both points in time. Expression of tumor necrosis factor α was more than 2-fold increased (P < .05) in the very early phase after induction of postoperative ileus but did not occur in mechanical bowel preparation-pretreated animals. Myeloperoxidase staining revealed that mechanical bowel preparation inhibited postoperative ileus-associated leukocyte infiltration of the intestinal muscularis at 3 and 9 hours after surgery, but not selective decontamination + mechanical bowel preparation treatment. The number of leukocytes after mechanical bowel preparation-only treatment remained at the level of sham-controls. ConclusionMechanical bowel preparation prevents permeability and leukocyte infiltration of the intestinal wall in the early phase of postoperative ileus in mice.

Measurement of low-grade inflammation of the esophageal mucosa with electrical conductivity shows promise in assessing PPI responsiveness in patients with GERD.

A device that can easily measure electrical impedance might be a helpful tool for investigating the pathophysiology of gastroesophageal reflux disease. The first aim of this study was to validate our newly developed bioelectrical admittance measurement (BAM) through in vitro experimentation. The second aim was to investigate whether evaluation of BAM by this measurement differed between patients with heartburn according to their response to proton pump inhibitor (PPI) therapy. Caco-2 cell monolayers and three-dimensional tissues were examined by BAM using a frequency response analyzer. BAM was also used to measure the impedance through cell layers. Subsequently, BAM was performed during endoscopy in 41 patients experiencing heartburn without esophageal mucosal breaks. After 2-wk administration of 20-mg rabeprazole twice daily, patient responses to PPI were classified as "good" or "poor" according to their clinical course. In each patient, histological alterations and gene expression levels of inflammation mediators and tight junction proteins were evaluated. Impedance profiles indicated that monolayer Caco-2 cells on top of eight-layered normal human dermal fibroblasts had the highest magnitude of impedance over the range of frequencies. In vivo results revealed that patients with good responses to PPI displayed significantly higher admittance. Severity of low-grade inflammation was significantly associated with esophageal wall admittance. Moreover, esophageal wall admittance may be more closely related to basal zone hyperplasia than dilatation of intercellular spaces. Thus, BAM may be able to detect abnormalities in the subepithelial layer of the esophagus.NEW & NOTEWORTHY Bioelectrical admittance measurement is a new method to evaluate esophageal mucosal permeability vertically during upper gastrointestinal endoscopy. Measurement of low-grade inflammation of the esophageal mucosa with electrical conductivity shows promise in assessing proton pump inhibitor responsiveness in patients with gastroesophageal reflux disease. As various gastrointestinal diseases are associated with changes in mucosal permeability, bioelectrical admittance measurement is expected to be clinically applied to therapeutic decision-making for these diseases in the future.

A102 MONOSODIUM GLUTAMATE INCREASES VISCERAL SENSITIVITY IN A MURINE MODEL OF IRRITABLE BOWEL SYNDROME

Abstract Background Over 70% of patients suffering from symptoms of the irritable bowel syndrome (IBS) report that food is the most common trigger. Patients have identified that monosodium glutamate (MSG) is one food component that they suspect can trigger symptoms, but this remains unproven. As a first step towards establishing a potential role, we sought to examine whether there was a plausible mechanism of how MSG ingestion could underlie exaggerated pain signaling in IBS. Aims To examine the effects of MSG on visceral sensitivity in a murine model of IBS. Methods Balb/c mice were subjected to 6-days of water-avoidance stress (WAS) to create a pre-clinical model for IBS. To assess changes in visceral afferent nerve sensitivity in control and WAS mice, responses to ramp distension (0–60 mmHg), in the absence and presence 10 μM MSG perfused into the intestinal lumen (concentration based on diet analysis of MSG human ingestion), were recorded from afferent nerves innervating the jejunum ex vivo. To quantify these responses, the baseline firing frequency (spikes/second) was subtracted from the maximum response at each distending pressure. The relative distension response was calculated as a percentage of the control distension response (absence of MSG) (Figure 1). Jejunal preparations from the same WAS-treated mice were also used to measure ex vivo changes in mucosal permeability to MSG using Ussing chambers. We also ran the same distension protocol; however, we applied 10 μM MSG directly to the organ bath outside intestine obtained from control mice. This direct application would allow the MSG to have direct access to the nerve terminals without having to traverse the mucosa. Results The intraluminal administration of 10 μM MSG significantly increased afferent nerve sensitivity in WAS-treated jejunum but not controls. This response was significantly greater (23%) at pressures between 40 and 60 mmHg (p&amp;lt;0.01) (Figure 1). WAS-treated mouse jejunum was also significantly more permeable to MSG (p&amp;lt;0.05). Furthermore, the application of 10 μM MSG directly to the bath containing healthy jejunum significantly increased by 25% the sensitivity of afferent nerves specifically at 60 mmHg (p&amp;lt;0.01). Conclusions Our findings demonstrate that MSG increases visceral sensitivity to distension in our pre-clinical model of IBS. The increased permeability to MSG in WAS tissue and increased distension response in healthy control tissue when MSG is applied directly to the bath rather than intraluminally, suggests that MSG signals to the immune compartment or directly to the afferent nerve terminals. These findings support the rationale for future in vivo studies with this model to further clarify the mechanism. Funding Agencies CCC, CIHR

Small intestinal permeability in older adults.

It is not yet clear whether intestinal mucosal permeability changes with advancing age in humans. This question is of high importance for drug and nutrition approaches for older adults. Our main objective was to answer the question if small intestinal barrier integrity deteriorates with healthy aging. We conducted a cross‐sectional study including the pooled data of 215 nonsmoking healthy adults (93 female/122 male), 84 of whom were aged between 60 and 82 years. After a 12‐h fast, all participants ingested 10 g of lactulose and 5 g of mannitol. Urine was collected for 5 h afterwards and analyzed for test sugars. The permeability index (PI = lactulose/mannitol) was used to assess small intestinal permeability. Low‐grade inflammation defined by high‐sensitivity C‐reactive protein ≥1 mL/L and kidney function (estimated glomerular filtration rate) were determined in the older age group. The PI was similar in older compared to younger adults (P =0.887). However, the urinary recovery of lactulose and mannitol was lower in the older adults and this change was neither associated with urinary volume nor glomerular filtration rate. The PI was not significantly correlated with low‐grade inflammation or presence of noninsulin‐dependent type 2 diabetes. However, it significantly deteriorated in the copresence of both conditions compared to low‐grade inflammation alone (P =0.043) or type 2 diabetes alone (P =0.015). Small intestinal mucosal barrier does not deteriorate with age per se. But low‐grade inflammation coupled with minor disease challenges, such as type 2 diabetes, can compromise the small intestinal barrier.

Small intestinal permeability in older adults

AbstractIt is not yet clear whether intestinal mucosal permeability changes with advancing age in humans. This question is of high importance for drug and nutrition approaches for older adults. Our main objective was to answer the question if small intestinal barrier integrity deteriorates with healthy aging. We conducted a cross‐sectional study including the pooled data of 215 nonsmoking healthy adults (93 female/122 male), 84 of whom were aged between 60 and 82 years. After a 12‐h fast, all participants ingested 10 g of lactulose and 5 g of mannitol. Urine was collected for 5 h afterwards and analyzed for test sugars. The permeability index (PI = lactulose/mannitol) was used to assess small intestinal permeability. Low‐grade inflammation defined by high‐sensitivity C‐reactive protein ≥1 mL/L and kidney function (estimated glomerular filtration rate) were determined in the older age group. The PI was similar in older compared to younger adults (P = 0.887). However, the urinary recovery of lactulose and mannitol was lower in the older adults and this change was neither associated with urinary volume nor glomerular filtration rate. The PI was not significantly correlated with low‐grade inflammation or presence of noninsulin‐dependent type 2 diabetes. However, it significantly deteriorated in the copresence of both conditions compared to low‐grade inflammation alone (P = 0.043) or type 2 diabetes alone (P = 0.015). Small intestinal mucosal barrier does not deteriorate with age per se. But low‐grade inflammation coupled with minor disease challenges, such as type 2 diabetes, can compromise the small intestinal barrier.

Sennoside-induced secretion is not caused by changes in mucosal permeability or Na+,K(+)-ATPase activity.

The effect of sennosides (50 mg kg-1) on the rat colon in-situ was studied 6 h after oral treatment when the laxative effect was maximal. In a second experiment, rhein (4 x 10(-3) M), an active sennoside metabolite, was administered into the lumen of the colon for 1 h. Both sennosides and rhein reduced net H2O and Na+ absorption or reversed it to net secretion. Paracellular permeability, as measured using erythritol as a small marker molecule, was increased 2- to 3-fold; permeability to a large molecule, PEG 1000, was unchanged. The activity of Na+,K(+)-ATPase in the colon mucosa was not affected. There was no damage of the epithelial cells as determined by lactic acid dehydrogenase release. These results indicate that neither inhibition of Na+,K(+)-ATPase nor damage of the colon epithelium are involved in the secretory effect of sennosides or rhein. The increased paracellular permeability of small molecules fits into the concept of stimulation of active chloride secretion by sennosides, which is electrochemically and osmotically balanced by an increase in Na+ and H2O flow via the paracellular pathway.

Microvascular and epithelial permeability measurements in laboratory animals

Disruption of the mucosal permeability barrier is an acute life-threatening consequence of intestinal transplantation. The major aim of organ preservation techniques is to maintain the mucosal barrier and its function. Thus, assessment of microvascular and epithelial permeability is an important tool to determine the efficacy of therapeutic interventions. The use of murine models is particularly advantageous, as numerous immunological approaches (e.g., monoclonal antibodies) and genetically modified animal strains have been developed. Large animal models are also useful because they allow online detection of mucosal permeability changes. In this review, we summarize the available methodologies for measuring microvascular and epithelial permeability in the intestines of laboratory animals. We describe the advantages of various photometric and intravital microscopic methods for the assessment of microvascular permeability. Techniques that determine the inward and outward direction of mucosal permeability changes (including radioenzymatic, fluorimetric, and intravital microscopy methods) are also discussed.

Role of the W07-toxin on Vibrio cholerae-induced diarrhoea.

Vibrio cholerae W07 strain isolated from a cholera epidemic in South India, lacked the ctx gene but could still secrete a novel toxin, the W07-toxin that could cause fluid accumulation in ligated rabbit ileal loop. The important intracellular messengers implicated in this study were Ca(2+), cyclic AMP, inositol triphosphate and protein kinase C (PKC). A number of inhibitors/channel blockers have further shown the major role of [Ca(2+)](i) in modulation of the toxin-induced cellular response. An increase in the level of reactive oxygen species (ROS) in the W07-toxin-stimulated enterocytes correlated with the decrease in the levels of antioxidant enzymes, catalase and superoxide dismutase (SOD). The reactive nitrogen intermediates (RNI) detected by measuring the levels of nitrite and citrulline, were found to be high in the enterocytes triggered with the W07-toxin, thereby indicating their role in toxin-mediated change in mucosal permeability. The precise role of the toxin has also been authenticated by conducting the experiments with W07-toxin preincubated in the presence of IgG(WT) (IgG isolated from antitoxin sera) or GM(1). Thus, a significant increase in the levels of second messengers and a decrease in antioxidant defenses appear to be important in mediating the fluid secretion caused by this novel toxin from V. cholerae W07.

Effect of Histamine on the Permeability of the Nasal Mucosa in vivo

Objective--Histamine is one of the chemical mediators released during the acute phase of allergic rhinitis and is considered to cause the increase in epithelial permeability observed. We tried to examine the effect of histamine on nasal mucosal permeability in vivo. Material and methods--Histamine at different concentrations was administered to the nostrils of healthy subjects and the nasal transepithelial potential difference (PD) was measured. We also examined nasal mucosal permeability by means of a histochemical technique using horseradish peroxidase (HRP) in guinea pigs. Results--Administration of 10−1 M histamine significantly reduced the nasal PD in healthy subjects. After administration of 5.4×10−1 M histamine to the noses of guinea pigs, most of the intercellular spaces showed positive reactions to HRP and this effect was significantly inhibited by pretreatment with mepyramine and the antihistamine bepotastine besilate. Conclusion--These results indicate that histamine plays an important role in the change in mucosal permeability observed in allergic rhinitis in vivo via the histamine H1 receptor.

Augmented increase in tight junction permeability by luminal stimuli in the non-inflamed ileum of Crohn's disease.

Crohn's disease is associated with deranged intestinal permeability in vivo, suggesting dysfunction of tight junctions. The luminal contents are important for development of neoinflammation following resection. Regulation of tight junctions by luminal factors has not previously been studied in Crohn's disease. The aim of the study was to investigate the effects of a luminal stimulus, known to affect tight junctions, on the distal ileum in patients with Crohn's disease. Surgical specimens from the distal ileum of patients with Crohn's disease (n=12) were studied, and ileal specimens from colon cancer patients (n=13) served as controls. Mucosal permeability to 51Cr-EDTA and electrical resistance were studied in Ussing chambers during luminal exposure to sodium caprate (a constituent of milk fat, affecting tight junctions) or to buffer only. The mechanisms involved were studied by mucosal ATP levels, and by electron and confocal microscopy. Baseline permeability was the same in non-inflamed ileum of Crohn's disease and controls. Sodium caprate induced a rapid increase in paracellular permeability--that is, increased permeation of 51Cr-EDTA and decreased electrical resistance--which was more pronounced in non-inflamed ileum of Crohn's disease, and electron microscopy showed dilatations within the tight junctions. Moreover, sodium caprate induced disassembly of perijunctional filamentous actin was more pronounced in Crohn's disease mucosa. Mucosal permeability changes were accompanied by mitochondrial swelling and a fall in epithelial ATP content, suggesting uncoupling of oxidative phosphorylation. The tight junctions in the non-inflamed distal ileum of Crohn's disease were more reactive to luminal stimuli, possibly mediated via disturbed cytoskeletal contractility. This could contribute to the development of mucosal neoinflammation in Crohn's disease.

Do eicosanoids cause colonic dysfunction in experimentalE coli 0157:H7 (EHEC) infection?

BACKGROUNDThe pathophysiology of enterohaemorrhagicEscherichia coli (EHEC) infection remains unclear. Eicosanoids have been implicated as pathophysiological mediators in other colitides.AIMSTo determine if prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) contribute to...

Upper gastrointestinal toxicity of alendronate

OBJECTIVE: Alendronate is rapidly gaining widespread use in the treatment of osteoporosis. However, recent postmarketing surveys and endoscopic studies suggest that its use may be associated with significant predictable esophageal and gastric mucosal toxicity, similar to that of aspirin and nonsteroidal anti-inflammatory drugs. Because treatment of osteoporosis may be needed in as many as 30% of all postmenopausal women, and considering that alendronate could be used in all postmenopausal women as prevention, definition of potential mucosal toxicity is crucial. Our aim was to study the upper gastrointestinal toxicity of alendronate in an age-appropriate female population using a clinically applicable dose (10 mg/day) to determine whether it causes predictable damage in the proximal gastrointestinal mucosa in a fashion similar to that seen with aspirin and nonsteroidal anti-inflammatory drugs. METHODS: We conducted a double-blind, randomized, placebo-controlled trial in 32 healthy female volunteers between the ages of 40 and 65 yr recruited by newspaper advertisement. Endoscopic mucosal abnormalities in the esophagus, stomach, and duodenum both before and after 1 month of treatment were scored and compared using validated endoscopic grading systems. Symptom scores before and after treatment were determined. Noninvasive measurements of gastrointestinal permeability were obtained before, during, and after treatment using sucrose and mannitol/lactulose urinary excretions. RESULTS: Endoscopic scores before and after treatment with alendronate were not significantly different. Similarly, mean symptom scores in the alendronate group did not change significantly after treatment. There were no significant mucosal permeability changes in the stomach or small intestine after treatment. CONCLUSION: Alendronate does not cause predictable esophageal, gastric, or duodenal mucosal damage when used as directed.

Gut mucosal atrophy after a short enteral fasting period in critically ill patients

Purpose: The purpose of this study was to evaluate the presence of gut mucosal atrophy and changes in mucosal permeability in critically ill patients after a short fasting period. Materials and Methods: Fifteen critically ill patients underwent a period of enteral fasting of at least 4 days (mean 7.8 days). We took the following measurements the day before initiating enteral nutrition: indirect calorimetry, serum albumin, prealbumin, and lymphocyte count. We also performed a duodenal endoscopic biopsy with histopathological and mucosal morphometric analysis including villus height and crypt depth. The lactulose-mannitol test was performed to assess gut permeability. A total of 28 healthy volunteers served as controls for duodenal biopsy or lactulose-mannitol test. Clinical data, such as length of fasting, severity score, and previous parenteral nutritional support, were recorded. Results: We found gut mucosal atrophy, expressed as a decrease in villus height and crypt depth, in patients compared with controls. The patients also exhibited an abnormal lactulose-mannitol test. Morphometric changes did not correlate with permeability. Further, we found no correlation between the results of the lactulose-mannitol test and of mucosal morphometry with clinical data. Conclusions: We found that a short period of enteral fasting was associated with significant duodenal mucosal atrophy and abnormal gut permeability in critically ill patients.

Improved Nasal Bioavailability of FITC-Dextran (Mw 4300) from Mucoadhesive Microspheres in Rabbits

The nasal bioavailability of fluorescein isothiocyanate-dextran (FITC-dextran) (Mw = 4300) encapsulated in non-mucoadhesive and mucoadhesive microspheres in New Zealand White rabbits was investigated. FITC-dextran was administered nasally encapsulated in carbopol 934P, chitosan and lactose microspheres and the bioavailability compared to intravenous administration of FITC-dextran solution. Administration of FITC-dextran as carbopol microspheres produced a significantly greater bioavailability (33%) than after administration as chitosan (13%) and non-mucoadhesive rapidly dissolving control lactose microspheres (9%). The FITC-dextran terminal plasma half-lives after carbopol 934P and chitosan microsphere administration were significantly longer than after intravenous administration of FITC-dextran. The FITC-dextran terminal plasma half-life after carbopol 934P microspheres administration was significantly longer than after lactose microsphere administration. This data suggested that the increase in FITC-dextran bioavailability after carbopol 934P microspheres administration was due to increased residence at the absorptive site via mucoadhesion and reduced mucociliary clearance. A change in mucosal permeability could not however be discounted especially for the chitosan microspheres.

Intestinal and systemic humoral immunological events in the susceptible Balb/C mouse strain after oral administration of Echinococcus multilocularis eggs.

The aim of the study was to investigate the systemic and, for the first time, the intestinal humoral events in the susceptible Balb/C mouse strain after oral administration of Echinococcus multilocularis eggs. Thirty-one mice were divided into three groups; W-2, W-8 and control group. Each mouse of the W-2 and W-8 groups was orally infected with 1,500 E. multilocularis eggs, two weeks and eight weeks before sacrifice respectively. Control group mice received phosphate buffer saline. Measurement of anti-E. multilocularis and non-specific IgG, IgA and IgM, and of a transudation marker, albumin, were performed in serum and intestinal washings by a time-resolved immunofluorometric assay. These results were complemented by microscopic examination of the intestinal mucosa. This infection model is well-suited to the study of mucosal immunity during alveolar echinococcosis. It showed a major specific intestinal response in the early stage of the disease whereas the systemic response predominated later in the disease. Histopathological studies and calculation of the relative coefficient of excretion of Ig also confirmed that the presence of the parasite, even during a short period, was responsible for a local immunological and inflammatory response and for a change in mucosal permeability. Mucosal immunity could thus play a role in tolerance induction against E. multilocularis that could be a prerequisite for the subsequent development of the larvae in the liver, and for the occurrence of the parasitic disease, alveolar echinococcosis.

Enhanced mucosal permeability and nitric oxide synthase activity in jejunum of mast cell deficient mice

Background—Recent reports have described a modulating influence of nitric oxide (NO) on intestinal mucosal permeability and have implicated a role for mast cells in this NO mediated process.Aims—To assess further...

Changes in mucosal permeability to lipopolysaccharide in the colon of chronic alcoholic rats.

To evaluate the effects of chronic alcohol abuse on mucosal permeability to lipopolysaccharide (LPS) in the colon of rats. Escherichia coli LPS (20 mg/L) was injected into the colon of chronic alcoholic rats (n = 10) that had been supplied with Lieber diet every other day for six weeks. Before and 5, 10, 20, and 30 min after LPS injection, portal vein blood samples were obtained and the LPS levels in the blood were measured. The distribution of LPS in the colon tissues was observed with confocal laser scanning microscopy by immunofluorescence technique using a monoclonal antibody specific to the lipid A region of LPS. Normal rats were used as the controls (n = 6). Before LPS injection, LPS levels in the portal vein blood of chronic alcoholic rats were significantly higher than that of the normal controls (3.56 ± 0.67 ng/L vs 2.45 ± 0.15 ng/L, P < 0.01). At 5, 10, 20, and 30 min after LPS injection, LPS levels were significantly higher than that before LPS injection (173.56 ± 3.45 ng/L, 154.78 ± 0.57 ng/L, 43.89 ± 0.67 ng/L, 45.38 ± 0.89 ng/L vs 3.56 ± 0.67 ng/L, respectively, P < 0.01). Most mucosal cells in the chronic alcoholic rats showed strong positive reactions to LPS, but in the normal rats, there were no significant changes in portal vein blood LPS levels and in the fluorescence reactions to LPS in the mucosal cells after LPS injection. Chronic alcohol abuse results in a significant increase in LPS permeability in the colon mucosa cells of rats.

Mucosal permeability after subclinical intestinal ischemia-reperfusion injury: An exploration of possible mechanisms

Changes in mucosal permeability may be important in the etiology of necrotizing enterocolitis. The authors have previously shown that subclinical ischemia-reperfusion injury results in increased permeability in the rat intestine, and have partially characterized this phenomenon. In the present study the authors attempt to determine the mechanism by which these changes occur. Six-week-old rats underwent 10-minute superior mesenteric artery occlusion (SMAO) or sham, and mucosal permeability to 51CrEDTA was measured after 30 minutes. Rats were pretreated with saline, inhibitors of oxygen free radicals (superoxide dismutase + catalase, vitamin E, allopurinol, α-phenyl-N-tert butyl-nitrone), inhibitors of eicosanoids (indomethacin, quinacrine, diethylcarbamazine, 13-azaprostanoic acid), the putative cytoprotective agent prostaglandin E 2, or the inhibitor of neutrophil free radical production fructose 1–6 diphosphate. None of the agents significantly attenuated the increase in mucosal permeability caused by SMAO, although indomethacin and prostaglandin E 2 significantly exacerbated the permeability changes. To further explore the role of neutrophils, tissue myeloperoxidase was measured 30 minutes after SMAO. There was no significant difference in myeloperoxidase levels between sham and SMAO animals. These data suggest that the early increase in mucosal permeability after subclinical ischemia-reperfusion injury is not mediated by oxygen free radicals, eicosanoids, or neutrophils. The deleterious effect of indomethacin and prostaglandin E 2 suggests a possible protective role for the cyclooxygenase system, but further studies are necessary to elucidate this possibility.

Luminal glutamine perfusion alters endotoxin-related changes in ileal permeability of the piglet.

The objective of this study was to investigate whether luminal perfusion with glutamine or with oxygenated glutamine solutions prevents endotoxin-induced changes in mucosal permeability. Three 15-cm segments of distal ileum were isolated in anesthetized 21-day-old piglets (n = 4) and perfused (50 mL/h) with Ringer's lactate solution, Ringer's lactate solution with 2% glutamine (wt/vol), glutamine, or glutamine purged with oxygen at 37 degrees C for 280 minutes. Plasma-to-lumen clearances of 51Cr-EDTA and urea were measured to assess mucosal permeability. At time 0 minutes, loading and maintenance IV infusions of markers were begun. Baseline permeabilities were obtained from time 60 to 80 minutes, and IV endotoxin (50 micrograms/kg) was introduced from time 80 to 140 minutes. Results are expressed as the ratio of the clearances of the two probes (CEDTA/CUREA). Permeability increased from baseline in loops perfused with Ringer's lactate solution vs loops perfused with glutamine purged with oxygen and with glutamine alone (p < .01). Saturation with oxygen was without effect inasmuch as glutamine alone negated permeability increases. Intestinal myeloperoxidase activity did not differ with perfusate (p > .05). These data suggest that endotoxin-induced permeability changes can be prevented or delayed by the supply of luminal glutamine at the time of insult.