Plasma Diamine Oxidase Research Articles

Suppression of TNF-α and free radicals reduces systematic inflammatory and metabolic disorders: Radioprotective effects of ginseng oligopeptides on intestinal barrier function and antioxidant defense

Irradiation therapy is markedly associated with intestinal injure and oxidant stress. This study aimed to investigate the effects of ginseng (Panax ginseng C.A. Mey.) oligopeptides (GOP) on irradiation-induced intestinal injury and antioxidant defense in mice. BALB/c mice (8 weeks old) were randomly divided into six groups: vehicle control, irradiation control (IR), IR+whey protein [0.30 g/kg body weight (BW)], IR+GOP 0.15 g/kg BW, IR+GOP 0.30 g/kg BW and IR+GOP 0.60 g/kg BW. Postirradiation 30-day survival trial, white blood cells count and bone marrow hematopoietic system damage were performed to identify the injury degree induced by irradiation. Then, histopathology analysis was observed and intestinal permeability in vivo was quantified with fluorescein isothiocyanate–dextran. The enzyme-linked immunosorbent assay was used to determine antioxidant ability, plasma inflammatory cytokines, diamine oxidase (DAO) and endotoxin (LPS) levels. The immunohistochemistry assay was used to analyze the expression levels of tight junction proteins. We found that GOP-treated mice exhibited lower concentrations of plasma LPS and DAO and decreased instructors of inflammatory and oxidative stress which were linked to the lower intestinal permeability and higher tight junction proteins expression. The blockage of GOP was linked with the reduction of TNF-α and free radicals. The 15-day pretreatment of GOP could exhibit radioprotective effects, and another 15-day posttreatment benefited the quick repair of irradiation-induced injury. We confirm that GOP would exhibit effective therapeutic value on attenuating irradiation-induced hematopoietic, gastrointestinal and oxidative injury in cancer patients.

Benzoic acid beneficially affects growth performance of weaned pigs which was associated with changes in gut bacterial populations, morphology indices and growth factor gene expression.

This study was conducted to investigate the effects of benzoic acid (BA) on growth performance, intestinal development and intestinal barrier function in weaned pigs. Ninety weaned pigs were randomly assigned to one of three treatments: a basal diet (CON), the basal diet supplemented with 2000mg/kg benzoic acid (BA1) and 5000mg/kg benzoic acid (BA2). At the end of days 14 and 42, six pigs per treatment were randomly selected to collect plasma and intestinal samples. Results showed that BA supplementation not only improved final body weight, daily growth and feed conversion ratio from days 15 to 42 and days 1 to 42, but also decreased the activity of plasma diamine oxidase (day 42) and the pH values of jejunal contents (day 14) (p<0.05). Ileal Bacillus populations (day 14) were increased by BA, while Escherichia coli counts in the ileum and caecum (day 42) were decreased (p<0.05). Higher Lactobacillus counts occurred in the ileum (day 14, 42) of BA1-fed piglets as compared to CON and BA2-fed piglets (p<0.05). In addition, BA supplementation increased the ratio of villus height to crypt depth (day 14, 42) and decreased the crypt depth (day 14) (p<0.05). Growth-stimulating factors (insulin-like growth factor-1, day 42; insulin-like growth factor-1 receptor, day 14, 42) and tight junction protein (occludin, day 14, 42; zonula occludens-1, day 42)-related gene mRNA levels were upregulated in the jejunum of piglets fed BA diets (p<0.05). In conclusion, this study provides the first evidence that BA has beneficial effects on intestinal development and intestinal barrier function of weaned pigs, which can partly explain why growth performance of pigs was improved by dietary BA supplementation.

Evaluating Intestinal Permeability by Measuring Plasma Endotoxin and Diamine Oxidase in Children with Acute Lymphoblastic Leukemia Treated with High-dose Methotrexate.

The incidence of acute lymphoblastic leukemia (ALL) is highest in childhood malignant tumor in China. The high-dose methotrexate (HDMTX) treatment is very effective in ALL, and it can improve event-free survival rate. However, while executing the anti-tumor effect, it produces highly toxic effects on rapidly dividing cells which are normal. It seems probable that the HDMTX treatment injures intestinal mucosal barrier. The changes of intestinal mucosal barrier can be evaluated through measuring the level of plasma endotoxin and diamine oxidase (DAO). Blood samples were collected from 30 normal children and 30 children with ALL at 1h, 24h, 44h and 68h after HDMTX. The levels of plasma endotoxin and DAO were measured at 1h, 24h, 44h and 68h after HDMTX with spectrophotometry. The levels of endotoxin and DAO were also measured in 4 different courses in 7 children with ALL. The levels of plasma endotoxin and DAO at 1h, 24h, 44h and 68h after HDMTX were higher than in normal children (P<0.01). The levels of plasma endotoxin and DAO at 24h and 44h after HDMTX were both higher than at 1h and 68h (P<0.01). There was no significant difference found in the measured results of plasma endotoxin and DAO at 1h and 68h after HDMTX (P>0.05). There was no significant difference found in the increased levels of endotoxin and DAO at 1h, 24h, 44h and 68h after HDMTX in 4 different courses of 7 children with ALL(P>0.05). By measuring the level of plasma endotoxin and DAO in children with ALL and during HDMTX chemotherapy, the results suggest that there is increased intestinal permeability.

Polysaccharides from Acanthopanax senticosus enhances intestinal integrity through inhibiting TLR4/NF-κB signaling pathways in lipopolysaccharide-challenged mice.

To investigate the role of polysaccharide from Acanthopanax senticosus (ASPS) on lipopolysaccharide (LPS)-induced intestinal injury, mice in three treatments were administrated orally with or without ASPS (300 mg/kg body weight) for 14 days, followed by challenge with LPS or saline. At 4 h post-injection, blood and intestinal samples of six mice / treatment were collected. The results showed ASPS ameliorated LPS-induced intestinal morphological deterioration, proven by improved villus height (P < 0.05) and villus height : crypt depth ratio (P < 0.05). ASPS also elevated the mucosal barrier of LPS-challenged mice, supported by reduced plasma diamine oxidase (DAO) activity (P < 0.05) and L-lactate (P < 0.05), increased mucosal DAO activity (P < 0.05) as well as enhanced intestinal tight junction proteins expression involving occludin-1 (P < 0.05) and zonula occludens-1 (P < 0.05). In addition, ASPS decreased LPS-induced secretion of inflammatory mediators, including tumor necrosis factor (TNF)-α (P < 0.05) and prostaglandin E2 (P < 0.05). Also, ASPS down-regulated messenger RNA expression of toll-like receptor 4 (TLR4) and its downstream signals, including myeloid differentiation factor 88 (P < 0.05), TNF-α receptor-associated factor 6 (P < 0.05), as well as nuclear factor (NF)-κB p65 (P < 0.05) and its protein expression. These findings suggest that ASPS improves intestinal integrity under inflammation conditions connected with inhibiting TLR4/NF-κB signaling pathways.

Effect of glucose-insulin-potassium on intestinal injury in endotoxemic rats

Objective To evaluate the effect of glucose-insulin-potassium (GIK) on intestinal injury in endotoxemic rats. Methods Sixty male Sprague-Dawley rats, weighing 200-250 g, were equally and randomly divided into endotoxemia group (lipopolysaccharide[LPS] group) and GIK group.LPS 8 mg/kg was injected intraperitoneally once a day for 3 times in total to establish the model of endotoxemia-caused intestinal injury.Starting from 2 h after the initial injection of LPS, normal saline was continuously infused at 4 ml·kg-1·h-1 in group LPS, and GIK 4 ml·kg-1·h-1 was infused intravenously in group GIK.Before establishment of the model, and at 3 and 5 days after establishment of the model, 10 rats in each group were sacrificed, and blood samples were collected from the abdominal aorta for determination of tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) and diamine oxidase (DAO) concentrations in plasma by enzyme-linked immunosorbent assay.TNF-α/IL-10 ratio was calculated.A segment of ileum of 2 cm in length, 20 cm from the ileocecal junction, was removed for microscopic examination.The degree of damage to the intestinal mucous membrane was scored according to Chiu. Results Compared with the values before establishment of the model, the plasma TNF-α/IL-10 ratio, DAO concentration, and Chiu's scores were significantly increased at 3 days after establishment of the model in the two groups, the plasma TNF-α/IL-10 ratio, DAO concentration, and Chiu's scores were increased at 5 days after establishment of the model in group LPS, and the plasma DAO concentration, and Chiu's scores were increased at 5 days after establishment of the model in group GIK (P<0.05). Compared with the values at 3 days after establishment of the model, the TNF-α/IL-10 ratio and plasma DAO concentration were significantly increased in group LPS, and the TNF-α/IL-10 ratio and plasma DAO concentration were decreased in group GIK at 5 days after establishment of the model in group GIK(P<0.05). Compared with group LPS, the TNF-α/IL-10 ratio, plasma DAO concentration, and Chiu's scores were significantly decreased at 3 and 5 days after establishment of the model in group GIK (P<0.05). Conclusion GIK can reduce intestinal injury in endotoxemic rats. Key words: Glucose; Insulin; Potassium; Endotoxemia; Intestine

Association of plasma diamine oxidase and intestinal fatty acid–binding protein with severity of disease in patient with heat stroke

ObjectivesThe aim of this study was to describe the role of intestinal fatty acid–binding protein (iFABP) and allergy-related diamine oxidase (DAO) in patients with heat stroke (HS). MethodsA total of 10 patients with HS in intensive care unit and 10 healthy volunteers were enrolled in this study. The plasma intestinal permeability markers iFABP and DAO were measured since the time of admission. The whole blood endotoxin was also assessed. The associations between iFABP, DAO, and endotoxin level were analyzed. Then, white blood cell count, procalcitonin, and C-reactive protein were examined. In addition, we also determined the levels of proinflammatory cytokines such as IL-1α, IL-6, and TNF-α. ResultsComparing with the healthy control, the plasma iFABP and DAO level in patients with HS increased significantly (P < .05). The kinetic curve showed that plasma iFABP and DAO level reached peak value at day 3 and day 4 after admission, respectively. The endotoxin level was positively correlated with iFABP and DAO level. We also observed a significantly increased level of procalcitonin and C-reactive protein but not white blood count in patients with HS. After treatment, the iFABP and DAO level decreased significantly (P < .05). A significant increase in level of IL-1α and IL-6 was also found in patients with HS. ConclusionsThe plasma concentrations of DAO and iFABP could reflect a better function of the intestinal mucosa barrier in patients with HS. Plasma iFABP and DAO level decreased significantly after the treatment and, thus, might be a predictor for the severity of HS.

Monitoring changes in plasma levels of pancreatic and intestinal enzymes in a model of pancreatic exocrine insufficiency – induced by pancreatic duct-ligation – in young pigs

PurposePlasma levels of pancreatic and intestinal enzymes were measured after pancreatic duct ligation (PDL) to monitor pancreatic exocrine insufficiency (PEI) in a model using young pigs. Material/methodsFive, 6 week-old pigs (10.9±0.2kg), underwent PDL while age-matched, un-operated pigs were used as controls. Plasma levels of immunoreactive cationic trypsinogen (IRCT), amylase, lipase, and diamine oxidase (DAO) activities were analyzed for 48 days after PDL, including 1 week of oral pancreatic enzyme supplementation (PES) with Creon®. ResultsPDL resulted in an arrested body growth and a rapid surge of pancreatic enzymes (IRCT, amylase and lipase) into the plasma. Nine days after PDL, the plasma levels of these pancreatic enzymes had decreased. IRCT then remained below the level in un-operated pigs while amylase only fell below control at 25 days. The intestinally derived marker DAO and plasma protein levels were unaffected by PDL but DAO decreased slightly with time in PEI pigs. One-week of oral PES restored body growth, but had little effect on pancreatic enzyme plasma levels, except for a tendency towards increased DAO. ConclusionsThe study showed that PEI developed within 1–2 weeks after PDL and that only IRCT is a reliable plasma enzyme marker for this. The reduced plasma DAO indicated that PEI also affected the intestines, while PES therapy restored growth of the PDL pigs and slightly increased plasma DAO, suggesting an improved intestinal function.

Dimethyl sulfoxide inhibits zymosan-induced intestinal inflammation and barrier dysfunction.

To investigate whether dimethyl sulfoxide (DMSO) inhibits gut inflammation and barrier dysfunction following zymosan-induced systemic inflammatory response syndrome and multiple organ dysfunction syndrome. Sprague-Dawley rats were randomly divided into four groups: sham with administration of normal saline (SS group); sham with administration of DMSO (SD group); zymosan with administration of normal saline (ZS group); and zymosan with administration of DMSO (ZD group). Each group contained three subgroups according to 4 h, 8 h, and 24 h after surgery. At 4 h, 8 h, and 24 h after intraperitoneal injection of zymosan (750 mg/kg), the levels of intestinal inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-10] and oxides (myeloperoxidase, malonaldehyde, and superoxide dismutase) were examined. The levels of diamine oxidase (DAO) in plasma and intestinal mucosal blood flow (IMBF) were determined. Intestinal injury was also evaluated using an intestinal histological score and apoptosis of intestinal epithelial cells was determined by deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The intestinal epithelial tight junction protein, ZO-1, was observed by immunofluorescence. DMSO decreased TNF-α and increased IL-10 levels in the intestine compared with the ZS group at the corresponding time points. The activity of intestinal myeloperoxidase in the ZS group was higher than that in the ZD group 24 h after zymosan administration (P < 0.05). DMSO decreased the content of malondialdehyde (MDA) and increased the activity of superoxide dehydrogenase (SOD) 24 h after zymosan administration. The IMBF was lowest at 24 h and was 49.34% and 58.26% in the ZS group and ZD group, respectively (P < 0.05). DMSO alleviated injury in intestinal villi, and the gut injury score was significantly lower than the ZS group (3.6 ± 0.2 vs 4.2 ± 0.3, P < 0.05). DMSO decreased the level of DAO in plasma compared with the ZS group (65.1 ± 4.7 U/L vs 81.1 ± 5.0 U/L, P < 0.05). DMSO significantly preserved ZO-1 protein expression and localization 24 h after zymosan administration. The TUNEL analysis indicated that the number of apoptotic intestinal cells in the ZS group was much higher than the ZD group (P < 0.05). DMSO inhibited intestinal cytokines and protected against zymosan-induced gut barrier dysfunction.

Electroacupuncture at Zusanli Prevents Severe Scalds-Induced Gut Ischemia and Paralysis by Activating the Cholinergic Pathway.

Severe burn injuries may result in gastrointestinal paralysis, and barrier dysfunction due to gut ischemia and lowered vagus excitability. In this study we investigate whether electroacupuncture (EA) at Zusanli (ST36) could prevent severe scalds-induced gut ischemia, paralysis, and barrier dysfunction and whether the protective role of EA at ST36 is related to the vagus nerve. 35% burn area rats were divided into six groups: (a) EAN: EA nonchannel acupoints followed by scald injury; (b) EA: EA at ST36 after scald injury; (c) VGX/EA: vagotomy (VGX) before EA at ST36 and scald injury; (d) VGX/EAN: VGX before EAN and scald injury; (e) atropine/EA: applying atropine before scald injury and then EA at ST36; (f) atropine/EAN: applying atropine before scald injury and then EA at nonchannel acupoints. EA at the Zusanli point significantly promoted the intestinal impelling ratio and increased the amount of mucosal blood flow after scald injury. The plasma diamine oxidase (DAO) and intestinal permeability decreased significantly after scald injury in the EA group compared with others. However, EA after atropine injection or cervical vagotomy failed to improve intestinal motility and mucosa blood flow suggesting that the mechanism of EA may be related to the activation of the cholinergic nerve pathway.

Sa2004 Effects of AVX-470m, an Oral Polyclonal Anti-TNF Antibody, on Survival and Biomarkers in a Murine Model of Gastrointestinal Acute Radiation Syndrome

Intestinal mucositis is a common side-effect in patients undergoing radiotherapy and poses a severe dose-limiting factor in treatment1. Identification of compounds that prevent radiationinduced mucositis and improve intestinal restitution may offer new therapeutic strategies for maintaining intestinalmucosal integrity in patients undergoing radiotherapy. Pathogenesis of mucositis involves production of pro-inflammatory cytokines and reactive oxygen metabolites2,3 and increased apoptosis in intestinal epithelium, leading to loss of intestinal structure and function4. STW 5 is an herbal multi-component preparation having potent anti-oxidant and anti-inflammatory properties in intestinal inflammatory disorders,5,6, making it an attractive candidate to study its potential usefulness in mucositis. Intestinal mucositis was induced experimentally in rats by exposing them to whole body irradiation from a Caesium 137 source at a radiation dose of 6 Gray. Three days later, rats developed intestinal mucositis, judged by histological examination of the small intestine and measurement of associated parameters in intestinal homogenates and serum. STW5 was given orally for 5 days to rats in graded doses of 2 10 ml/kg before exposing them to radiation and continued for 3 days after exposure. Animals were sacrificed 24h later. Pretreatment with STW 5 led to dosedependent reduction in histological changes. A dose of 5 ml/kg was chosen to study in detail the protective effects of the preparation on relevant associated parameters. Histologically, irradiation caused shortening and fusion of villi, activation of mucus secreting glands, inflammatory cell infiltration of lamina propria and mucosal atrophy. Inflammation markers: tumor necrosis factor and myeloperoxidase activity in homogenates were also raised. The changes were associated with a rise in thiobarbituric acid reactive substances, reduction in glutathione and in protein content of intestinal homogenates. Biomarkers of intestinal tissue injury: plasma diamineoxidase was raised while citrulline7 was significantly reduced. Apoptosis was evidenced by a rise in cytosolic calcium, depletion of mitochondrial cytochrome c and B-cell lymphoma 2. Most histological changes and associated derangement in the parameters tested were largely prevented by STW 5. The findings pave the way to a new therapeutic approach in management of radiation induced mucositis. 1Costa G and Donaldson SS (1979) N Engl J Med 300, 1471-1474, 2MacNaughton WK (2000) Aliment Pharmacol Ther. 14, 523-528, 3Linard C et al (2003) Am J Physiol Gastrointest Liver Physiol. 285, 556-565, 4Wong TC et al (2006) J Pain Symptom Manage. 32, 27-37, 5Khayyal MT et al (2006) Phytomedicine. 13 Suppl 5, 56-66, 6Schempp H et al (2006) Phytomedicine. 2006;13 Suppl 5, 36-44 7Lutgens L and Lambin P (2007) World J. Gastroenterol., 13, 3033 3042

Are There Any Different Effects of Bifidobacterium, Lactobacillus and Streptococcus on Intestinal Sensation, Barrier Function and Intestinal Immunity in PI-IBS Mouse Model?

Background and AimsResearch has increasingly suggested that gut flora plays an important role in the development of post-infectious irritable bowel syndrome (PI-IBS). Studies of the curative effect of probiotics for IBS have usually been positive but not always. However, the differences of treatment effects and mechanisms among probiotic stains, or mixture of them, are not clear. In this study, we compared the effects of different probiotics (Befidobacterium, Lactobacillus, Streptococcus or mixture of the three) on intestinal sensation, barrier function and intestinal immunity in PI-IBS mouse model.MethodsPI-IBS model was induced by Trichinella spiralis infection in mice. Different probiotics were administered to mice after 8 weeks infection. Visceral sensitivity was measured by scores of abdominal withdrawal reflex (AWR) and the threshold intensity of colorectal distention. Colonic smooth muscle contractile response was assessed by contraction of the longitudinal muscle strips. Plasma diamine oxidase (DAO) and d-lactate were determined by an enzymatic spectrophotometry. Expression of tight junction proteins and cytokines in ileum were measured by Western blotting.ResultsCompared to control mice, PI-IBS mice treated either alone with Befidobacterium or Lactobacillus (but not Streptococcus), or the mixture of the three exhibited not only decreased AWR score and contractile response, but also reduced plasma DAO and D-lactate. These probiotic treatments also suppressed the expression of proinflammatory cytokine IL-6 and IL-17 and promoted the expression of major tight junction proteins claudin-1 and occludin. The mixture of the three probiotic strains performed better than the individual in up-regulating these tight junction proteins and suppressing IL-17 expression.Conclusions Bifidobacterium and Lactobacillus, but not Streptococcus, alleviated visceral hypersensitivity and recovered intestinal barrier function as well as inflammation in PI-IBS mouse model, which correlated with an increase of major tight junction proteins. In addition, Mixture of three species was indicated to be superior to a single one.

Protective effect of epigallocatechin-3-gallate in the intestinal mucosal barrier injury of severe acute pancreatitis in rats

Objective The study was designed to investigate the intestinal mucosa barrier function changes in rats with severe acute pancreatitis (SAP),and the intervention effect of epigallocatechin-3-gallate(EGCG) injection and its mechanisms of protection on intestinal mucosa barrier function injury of SAP with the purpose of providing evidence for preventing and curing intestinal mucosa barrier function injury of SAP in clinical practice.Methods A total of 80 healthy male Sprauge-Dawley (SD) rats were randomly divided into a normal group (Normal),a sham-operation group (Sham),a SAP model group (Model),and a EGCG treated group (EGCG),with 24 rats (except 8 rats in the normal group) in each group.The latter three groups each had three subgroups at three time points:6,12,24hours.Rats with SAP were prepared with retrograde cholangiopancreatic duct infusion in 5％ sodium taurocholate.The dynamic changes of the indexes of intestinal mucosa barrier function injury and Pancreas injury were observed at various time points in each group,including the levels of Plasma diamine oxidase (DAO) and serum amylase and malondialdehyde (MDA),nitric oxide(NO),inducible nitric oxide synthase(iNOS)in gut.Results 1.The levels of serum amylase [(3158.64 ± 218.25)μ/L,(4277.24 ± 231.35)μ/L,(5842.76 ± 248.18)μ/L] and plasma DAO concentration [(4.23 ± 0.51) μ/L,(5.13 ± 0.32)μ/L,(7.83 ± 0.76) μ/L] in the Model group were significantly higher at 6 h,12 h,24 h postoperation than the Normal group[serum amylase:(2074.11 ± 101.56)μ/L,DAO:(2.32 ± 0.48) μ/L] and Sham group [serum amylase:(1885.27 ± 103.89) μ/L,(1778.57 ± 98.94) μ/L,(1935.24 ± 105.87) μ/L].The levels of serum amylase [(2576.70 ± 123.43) μ/L,(2783.77 ± 155.53) μ/L,(2902.32 ±176.25) μ/L] and plasma DAO concentration (3.59 ± 0.57) μ/L,(3.98 ± 0.67) μ/L,(6.44 ± 0.71) μ/L in the EGCG group were lower than the Model group,but higher than the Normal group and the Sham group.Compared with the Normal group and the Sham group,the concentration of MDA and NO [MDA:(2.28±0.35) μmol/g,(3.02 ± 0.41) μmol/g,(3.78 ± 0.48) μmol/g ; NO:(16.80 ± 0.60) μmol/g,(18.23 ± 0.78) μmol/g,(20.14±0.82) μ,mol/g] significantly increased in the Model group at 6h,12 h,and 24 h postoperation.The concentration of MDA and NO (1.67±0.14) μmol/g,(1.75±0.16) μmol/g,(1.84±0.22) μmol/g; NO:(9.09±0.31) μmol/g,(9.32±0.44)μmol/g,(10.15±0.52)μmol/g were lower in the EGCG group in all times than the Model group.Compared with the Normal group (0.10) and the Sham group (0.25).The expression ofiNOS was significantly increased in the Model group(1.86).The expression of iNOS was lower in the EGCG group (0.66) in all times than the Model group,but higher than the Normal group and the sham group (P＜0.05).Conclusion Conclusion EGCG can protect the damages of intestinal mucosa barrier function in SAP rats,probably through reducing free radicals,and the iNOS expression. Key words: EGCG; Severe acute pancreatitis; Intestinal mucosa barrier function; Free radicals

Surveillance of Intra-Abdominal Pressure and Intestinal Barrier Function in a Rat Model of Acute Necrotizing Pancreatitis and Its Potential Early Therapeutic Window

ObjectivesTo monitor intra-abdominal pressure (IAP) and intestinal barrier function in a rat model of acute necrotizing pancreatitis (ANP) to elucidate a potential relevant therapeutic window.MethodsSprague-Dawley rats were randomly divided into experimental or control groups. The ANP group (n = 40) was injected with 4.5% sodium taurocholate into the pancreatic duct to induce ANP. The controls received only abdominal opening surgery (sham-operated, SO; n = 40) or no treatment or surgery (baseline; 0 h, n = 20). The SO and ANP groups were then randomly subdivided into 3, 6, 12 and 24 h groups (n = 10 each). IAP was measured at each time point and the rats were sacrificed to measure the weight of accumulated ascites fluid and the amylase, endogenous creatinine (Cr), total bilirubin (TB), tumor necrosis factor- alpha (TNF-alpha), diamine oxidase (DAO), and D-lactate. Mortality and the development of pathological changes in the pancreas and intestines were also monitored.ResultsIAP showed a continuous upward trend in the ANP group, with values 2 to 3 times higher than those in the SO group at the corresponding time points and the rising rate was peaking at 6 h. The levels of plasma amylase, TNF-alpha, Cr, TB, DAO, and D-lactate also gradually increased in the ANP group over time and were significantly higher than in the SO group at 3, 6, 12 and 24 h (all P<0.05). Moreover, the rising rate of TNF-alpha, DAO, and D-lactate also peaked at 6 h.ConclusionsThe ANP-induced changes in IAP, inflammatory factors and intestinal barrier that we observed in the rat model were especially obvious at 6 h post-induction, suggesting an early therapeutic window for the treatment of ANP in humans.

Diamine oxidase as a marker of intestinal mucosal injury and the effect of soluble dietary fiber on gastrointestinal tract toxicity after intravenous 5-fluorouracil treatment in rats

The level of plasma diamine oxidase (DAO) activity is associated with the maturation and integrity of small intestinal mucosa. This study in rats investigated whether a decreased level of plasma DAO could reflect the severity of mucosal injury due to intravenous 5-fluorouracil (5-FU) treatment. The beneficial effect of soluble dietary fiber (SDF) on preventing diarrhea after 5-FU treatment was also examined. To induce diarrhea, 5-FU (50 mg/kg/day for four days) was administered via the tail vein with or without SDF supplementation. After 5-FU treatment, the majority of rats developed moderate to severe diarrhea, and levels of plasma DAO activity significantly decreased compared to those of control group (P < 0.05). Scanning electron microscopy revealed disarrangement of the small intestinal villi. Contrarily, the rats supplemented with SDF had diarrhea less frequently (50.0 vs. 91.7 %, P = 0.025) on day five, and DAO activity levels were significantly higher than in those rats administered 5-FU alone (8.25 ± 5.34 vs. 5.50 ± 4.32, P = 0.023). In conclusion, plasma DAO activity decreases in response to severe intestinal mucosal injury after 5-FU treatment, and SDF supplementation might be a practical and useful treatment for reducing the intestinal toxicity of 5-FU.

Effect of early enteral nutrition on postoperative nutritional status and immune function in elderly patients with esophageal cancer or cardiac cancer.

To explore the effect of early enteral nutrition (EN) on postoperative nutritional status, intestinal permeability, and immune function in elderly patients with esophageal cancer or cardiac cancer. A total of 96 patients with esophageal cancer or cardiac cancer who underwent surgical treatment in our hospital from June 2007 to December 2010 were enrolled in this study. They were divided into EN group (n=50) and parenteral nutrition (PN) group (n=46) based on the nutrition support modes. The body weight, time to first flatus/defecation, average hospital stay, complications and mortality after the surgery as well as the liver function indicators were recorded and analyzed. Peripheral blood samples were collected on the days 1, 4 and 7 after surgery. The plasma diamine oxidase (DAO) activity and D-lactate level were determined to assess the intestinal permeability. The plasma endotoxin levels were determined using dynamic turbidimetric assay to assess the protective effect of EN on intestinal mucosal barrier. The postoperative blood levels of inflammatory cytokines and immunoglobulins were determined using enzyme-linked immunosorbent assay (ELISA). After the surgery, the time to first flatus/defecation, average hospital stay, and complications were significantly less in the EN group than those in the PN group (P<0.05), whereas the EN group had significantly higher albumin levels than the PN group (P<0.05). On the 7th postoperative day, the DAO activity, D-lactate level and endotoxin contents were significantly lower in the EN group than those in the PN group (all P<0.05). In addition, the EN group had significantly higher IgA, IgG, IgM, and CD4 levels than the PN group (P<0.05) but significantly lower IL-2, IL-6, and TNF-α levels (P<0.05). In elderly patients with esophageal cancer or cardiac cancer, early EN after surgery can effectively improve the nutritional status, protect intestinal mucosal barrier (by reducing plasma endoxins), and enhance the immune function.

Characterization of diamine oxidase from human seminal plasma

Diamine oxidase (DAO) was purified to homogeneity from human seminal plasma by consecutive chromatographic fractionation on heparin-sepharose, phenyl-sepharose, CIM-QA, and Superdex 200. Human seminal plasma DAO behaves electrophoretically similar to DAO proteins from other human tissues and has very similar enzymatic properties with histamine and aliphatic diamines being the preferred substrates as well as significant conversion of polyamines. The cellular source and functional importance of DAO in human semen remain to be determined.

A combination of plasma DAO and citrulline levels as a potential marker for acute mesenteric ischemia

IntroductionThere is no valid and reliable diagnostic test for early diagnosis of acute mesenteric ischemia (AMI). The aim of this study was to measure the plasma levels of diamine oxidase (DAO) and citrulline in AMI to gain insight into its early diagnosis.Material and methodsA total of 21 Wistar albino rats were divided into three groups, that is, control group, short-term ischemia group, and prolonged ischemia group. The superior mesenteric artery was occluded for 15 min in the short-term ischemia group and for 12 h in the prolonged ischemia group. Twelve hours later, the experiment was terminated and plasma DAO and citrulline levels were measured. Intestinal tissue was evaluated for the histopathological changes.ResultsCompared to the control group, the short-term and prolonged ischemia groups showed significant increases in the plasma levels of DAO, whereas the plasma citrulline levels decreased significantly. Prolonged ischemia caused a larger increase in the plasma DAO levels and a larger decrease in the plasma citrulline levels compared to the short-term ischemia (p=0.011 and p=0.021, respectively). Intestinal damage was shown to develop more in the prolonged ischemia group (p=0.001).ConclusionIn the early period of AMI, the plasma DAO levels increase while citrulline levels decrease, and the extent of these changes depends on the duration of ischemia.

Lack of Association of Plasma Histamine with Diamine Oxidase in Chronic Idiopathic Urticaria

BackgroundChronic idiopathic urticaria (CIU) is considered a complex and multifactorial disease. Excessive histamine intake may induce an attack of urticaria. The main enzyme for histamine metabolism is diamine oxidase (DAO).ObjectivePlasma histamine concentrations and DAO activities were evaluated to determine whether there are abnormalities in the histamine metabolism of CIU patients.MethodsSeventy-five CIU patients and twenty-five healthy control subjects were included in the study. Blood was taken from all subjects to measure plasma levels of the histamine and DAO.ResultsMean plasma histamine levels were significantly higher in CIU patients (11.59±10.98 nM) than in the control subjects (8.75±2.55 nM) (p=0.04). Mean DAO activities were lower in patients of CIU (80.86±26.81 histamine degrading unit [HDU]/ml) than in the controls (81.60±9.67 HDU/ml), but without significant difference. In 15 CIU patients with gastrointestinal symptoms, the mean histamine concentration was higher (12.43±7.97 nM) and DAO activity was lower (77.93±27.53 HDU/ml) than in the remaining 60 CIU patients without gastrointestinal symptoms (11.38±11.67 nM and 81.58±26.82 HDU/ml), without significant difference. The relationship between DAO activity and plasma histamine concentrations showed a significant negative linear value (p=0.001). There were no significant relationships between plasma histamine concentrations and symptom severity score.ConclusionIn CIU patients, a high plasma histamine concentration may not be explained by DAO activity. CIU patients with gastrointestinal (GI) symptoms showed no significantly lower DAO activity. Larger group studies are required to elucidate the relationship between plasma histamine concentrations and DAO activity, especially of CIU patients with GI symptomsto understand the difference in CIU patients with and without GI symptoms.

Fish Oil Enhances Intestinal Integrity and Inhibits TLR4 and NOD2 Signaling Pathways in Weaned Pigs after LPS Challenge1–3

Long-chain (n-3) PUFA exert beneficial effects on inflammatory bowel diseases in animal models and clinical trials. In addition, pattern recognition receptors such as toll-like receptors (TLR) and nucleotide-binding oligomerization domain proteins (NOD) play a critical role in intestinal inflammation. We hypothesized that fish oil could alleviate Escherichia coli LPS-induced intestinal injury via modulation of TLR4 and NOD signaling pathways. Twenty-four weaned piglets were used in a 2 × 2 factorial design and the main factors included a dietary treatment (5% corn oil or 5% fish oil) and immunological challenge (LPS or saline). After feeding fish oil or corn oil diets for 21 d, pigs were injected with LPS or saline. At 4 h postinjection, blood samples were collected and pigs were killed. EPA, DHA, and total (n-3) PUFA were enriched in intestinal mucosa through fish supplementation. Fish oil improved intestinal morphology, indicated by greater villus height and villus height:crypt depth ratio, and intestinal barrier function, indicated by decreased plasma diamine oxidase (DAO) activity and increased mucosal DAO activity as well as enhanced protein expression of intestinal tight junction proteins including occludin and claudin-1. Moreover, fish oil decreased intestinal TNFα and PGE2 concentrations and caspase-3 and heat shock protein 70 protein expression. Finally, fish oil downregulated the mRNA expression of intestinal TLR4 and its downstream signals myeloid differentiation factor 88, IL-1 receptor-associated kinase 1, TNFα receptor-associated factor 6, and NOD2, and its adaptor molecule, receptor-interacting serine/threonine-protein kinase 2. Fish oil decreased the protein expression of intestinal NFĸB p65. These results indicate that fish oil supplementation is associated with inhibition of TLR4 and NOD2 signaling pathways and concomitant improvement of intestinal integrity under an inflammatory condition.

Glucagonlike Peptide 2 Protects Intestinal Barrier in Severe Acute Pancreatitis Through Regulating Intestinal Epithelial Cell Proliferation and Apoptosis

To investigate the protective effect of glucagon-like peptide 2 (GLP-2) on intestinal barrier dysfunction in severe acute pancreatitis and to explore the putative mechanism of this effect. Thirty rats were randomly divided into 3 groups. Group 1 received sham operation. Severe acute pancreatitis was induced in group 2 and group 3 via retrograde injection of 3% sodium taurocholate to the pancreatic duct. Rats in group 3 were peritoneally injected with GLP-2. Intestinal barrier dysfunction was characterized by the histological measurements and concentration of plasma diamine oxidase. The tissue sections of ileum were collected for the detection of proliferating cell nuclear antigen protein and apoptosis. Glucagon-like peptide 2 administration improved the ileal mucosal injury, which was also demonstrated by the histological score of ileal mucosa. The concentration of diamine oxidase was decreased in rats with acute pancreatitis treated with GLP-2. Acute pancreatitis-induced epithelial cell apoptosis was partly prevented by GLP-2. Immunohistochemical staining of proliferating cell nuclear antigen protein was increased in group 3 compared with that in group 2. Results from this study suggest that GLP-2 has a protective effect on intestinal barrier dysfunction in rats with severe acute pancreatitis via mechanisms closely involving promotion of cell growth and inhibition of intestinal epithelial cell apoptosis.