Effects of N-acetylcysteine on the inflammatory response and bacterial translocation in a model of intestinal obstruction and ischemia in rats

Purpose: To evaluate effect of N-acetylcysteine (NAC) associated with Ringer lactate or hypertonic saline in inflammation and bacterial translocation on experimental intestinal obstruction (IO). Methods: Wistar rats was subjected to IO. Six or 24 hours after, rats were subjected to enterectomy and fluid resuscitation: IO, RL (subjected to the same procedures but with fluid resuscitation using Ringer's lactate solution); RLNAC (added NAC to Ringer's solution); and HSNAC (surgical procedure + fluid reposition with 7.5% hypertonic saline and NAC). After 24 h, tissues were collected to cytokines, bacterial translocation, and histological assessments. Results: In kidney, interleukin-1beta (IL-1beta) was lower in the groups with fluid resuscitation compared to IO group. The RLNAC showed lower levels compared to the RL. Interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha), and (IFN-gamma) were lower in the treatment groups than in IO. In lung, IL-1beta and IL-6 were lower in RLNAC compared to IO. IL-10 was lower in RL, RLNAC and HSNAC compared to IO. TNF-alpha was higher in HSNAC compared to both RL and RLNAC. Bacterial translocation was observed in all animals of IO group. In kidneys, inflammation and congestion degrees were lower in HSNAC compared to RL. In lungs, inflammation levels were higher in RLNAC compared with the sham group. Conclusions: The data indicates that NAC associated with RL can promote a decrease in the inflammatory process in the kidneys and lungs in rats, following intestinal obstruction and ischemia in rats.

Anti-inflammatory and antioxidant effects of the nanocomposite Fullerol decrease the severity of intestinal inflammation induced by gut ischemia and reperfusion.

Intestinal ischemia is a vascular emergency that arises when blood flow to the intestine is compromised. Reperfusion is necessary to restore intestinal function but might lead to local and systemic inflammatory responses and bacterial translocation, with consequent multiple organ dysfunction syndrome (MODS). During reperfusion occurs production of reactive oxygen species. These species contribute to intestinal injury through direct toxicity or activation of inflammatory pathways. Fullerol is a nanacomposite which has been shown to act as reactive oxygen species and reactive nitrogen species (RNS) scavengers. Thus, our aim was to evaluate whether Fullerol confer anti-inflammatory activity during intestinal ischemia and reperfusion (IIR). Intestinal ischemia was induced by total occlusion of the superior mesenteric artery. Groups were treated with vehicle or Fullerol 10 min before reperfusion. Mice were euthanized after 6 h of reperfusion, and small intestines were collected for evaluation of plasma extravasation, leukocyte influx, cytokine production and histological damage. Bacterial translocation to the peritoneal cavity and reactive oxygen and nitrogen species production by lamina propria cells were also evaluated. Our results showed that treatment with Fullerol inhibited bacterial translocation to the peritoneal cavity, delayed and decreased the lethality rates and diminished neutrophil influx and intestinal injury induced by IIR. Reduced severity of reperfusion injury in Fullerol-treated mice was associated with blunted reactive oxygen and nitrogen species production in leukocytes isolated from gut lamina propria and decreased production of pro-inflammatory mediators. Thus, the present study shows that Fullerol is a potential therapy to treat inflammatory bowel disorders associated with bacterial translocation, such as IIR.

Prophylactic and therapeutic supplementation using fructo-oligosaccharide improves the intestinal homeostasis after mucositis induced by 5- fluorouracil.

The beneficial effects of prebiotic, such as fructo-oligosaccharides (FOS), in intestinal inflammation have been demonstrated in several studies. Herein, we evaluate whether joint treatment with FOS, both before and during mucositis, had additional beneficial effects and investigated the mechanisms underlying in the action of FOS on the intestinal barrier. BALB/c mice were randomly divided into five groups: CTR (without mucositis + saline solution), FOS (without mucositis + 6 % FOS), MUC (mucositis + saline solution), PT (mucositis + 6 % FOS supplementation before disease induction), and TT (mucositis + 6 % FOS supplementation before and during disease induction). Mucositis was induced by intraperitoneal injection (300 mg/kg) of 5-fluorouracil (5-FU). After 72 h, the animals were euthanized and intestinal permeability (IP), tight junction, bacterial translocation (BT), histology and morphometry, and immunoglobulin A secretory (sIgA), inflammatory infiltrate, and production of short-chain fatty acids (acetate, butyrate and propionate) were evaluated. The MUC group showed an increase in the IP, BT, and inflammatory infiltrate but a decrease in the tight junction expression and butyrate and propionate levels (P < 0.05). In the PT and TT groups, FOS supplementation maintained the IP, tight junction expression, and propionate concentration within physiologic levels, increased butyrate levels, and reduced BT and inflammatory infiltrate (P < 0.05). Total treatment with FOS (TT group) was more effective in maintaining histological score, morphometric parameters, and sIgA production. Thus, total treatment (prophylactic and therapeutic supplementation) with FOS was more effective than pretreatment alone, in reducing 5-FU-induced damage to the intestinal barrier.

Conjugated linoleic acid prevents damage caused by intestinal mucositis induced by 5-fluorouracil in an experimental model.

BACKGROUND: Studies have showed the protective effects of conjugated linoleic acid (CLA) on intestinal epithelium, modulating host immune and inflammatory responses on intestinal diseases. OBJECTIVE: To evaluate the preventive effects of CLA on the intestinal mucositis induced by 5-FU in a murine model. METHODS: Sixty-four BALB/c mice were randomly divided into four groups: Control (CTL), fed a standard chow diet; CLAs, fed a diet supplemented with CLA; Mucositis (5-FU), fed a standard chow diet and underwent mucositis induction and CLAs 5-FU, fed a diet supplemented with CLA and underwent mucositis induction. Mucositis was induced by intraperitoneal injection of 300 mg/kg 5-FU. After 72 h, the animals were euthanized and intestinal permeability, bacterial translocation, inflammatory mediators, and intestinal histology were evaluated. RESULTS: Mice in the CLAs 5-FU group showed reduced weight loss compared to those in the 5-FU group (p < 0.005). Furthermore, the results also showed that the treatment with CLA reduced intestinal permeability, bacterial translocation, and biomarkers of inflammatory response besides minor damage to ZO-1 and occludin with maintenance of the integrity of the intestinal epithelium and a favorable balance between the inflammatory and regulatory cytokines. CONCLUSION: This study suggests that CLA reduced the adverse effects from 5-FU administration on the intestinal mucosa.

The effect of amifostine on bacterial translocation after radiation induced acute enteritis.

PURPOSE: To investigate the effects of amifostine on bacterial translocation and overgrowth in colonic flora after acute radiation enteritis in a rat model. METHODS: Thirty-two female Wistar albino rats were divided into four groups: Group-1 (n=8): only normal saline was administered intraperitoneally. Group-2 (n=8): first serum saline was administered intraperitoneally and 30 minutes later 20 Gy radiation was applied to abdominopelvic region. Group-3 (n=8): only amifostine 200 ml/kg was administered intraperitoneally and radiation was not applied. Group-4 (n=8): first amifostine 200 ml/kg was administered intraperitoneally and 30 minutes later 20 Gy radiation was applied to abdominopelvic region. On the 5th day after radiation, samples of mesenteric lymph tissues and cecal contents were taken by laparotomy for microbiological culture. RESULTS: Intraperitoneal amifostine administration significantly decreased the bacterial overgrowth related to radiation in colon but did not significantly decrease the bacterial translocation. CONCLUSION: Although not providing a full protection on the damaged mucosal barrier, amifostine significantly decreased the bacterial overgrowth in the cecal content after high dose radiation. There is a need to find out appropriate amifostine dose under different radiation applications avoiding bacterial translocation in gastrointestinal system.

The effect of amifostine on bacterial translocation after radiation induced acute enteritis

ABSTRACT PURPOSE: To investigate the effects of amifostine on bacterial translocation and overgrowth in colonic flora after acute radiation enteritis in a rat model. METHODS: Thirty-two female Wistar albino rats were divided into four groups: Group-1 (n=8): only normal saline was administered intraperitoneally. Group-2 (n=8): first serum saline was administered intraperitoneally and 30 minutes later 20 Gy radiation was applied to abdominopelvic region. Group-3 (n=8): only amifostine 200 ml/kg was administered intraperitoneally and radiation was not applied. Group-4 (n=8): first amifostine 200 ml/kg was administered intraperitoneally and 30 minutes later 20 Gy radiation was applied to abdominopelvic region. On the 5th day after radiation, samples of mesenteric lymph tissues and cecal contents were taken by laparotomy for microbiological culture. RESULTS: Intraperitoneal amifostine administration significantly decreased the bacterial overgrowth related to radiation in colon but did not significantly decrease the bacterial translocation. CONCLUSİON: Although not providing a full protection on the damaged mucosal barrier, amifostine significantly decreased the bacterial overgrowth in the cecal content after high dose radiation. There is a need to find out appropriate amifostine dose under different radiation applications avoiding bacterial translocation in gastrointestinal system.

Dietary glutamine prevents the loss of intestinal barrier function and attenuates the increase in core body temperature induced by acute heat exposure.

Dietary glutamine (Gln) supplementation improves intestinal function in several stressful conditions. Therefore, in the present study, the effects of dietary Gln supplementation on the core body temperature (T core), bacterial translocation (BT) and intestinal permeability of mice subjected to acute heat stress were evaluated. Male Swiss mice (4 weeks old) were implanted with an abdominal temperature sensor and randomly assigned to one of the following groups fed isoenergetic and isoproteic diets for 7 d before the experimental trials: group fed the standard AIN-93G diet and exposed to a high ambient temperature (39°C) for 2 h (H-NS); group fed the AIN-93G diet supplemented with l-Gln and exposed to a high temperature (H-Gln); group fed the standard AIN-93G diet and not exposed to a high temperature (control, C-NS). Mice were orally administered diethylenetriaminepentaacetic acid radiolabelled with technetium (99mTc) for the assessment of intestinal permeability or 99mTc-Escherichia coli for the assessment of BT. Heat exposure increased T core (approximately 41°C during the experimental trial), intestinal permeability and BT to the blood and liver (3 h after the experimental trial) in mice from the H-NS group relative to those from the C-NS group. Dietary Gln supplementation attenuated hyperthermia and prevented the increases in intestinal permeability and BT induced by heat exposure. No correlations were observed between the improvements in gastrointestinal function and the attenuation of hyperthermia by Gln. Our findings indicate that dietary Gln supplementation preserved the integrity of the intestinal barrier and reduced the severity of hyperthermia during heat exposure. The findings also indicate that these Gln-mediated effects occurred through independent mechanisms.

Effects of nitric oxide synthase inhibition on glutamine action in a bacterial translocation model.

Glutamine may be a precursor for NO synthesis, which may play a crucial role in bacterial translocation (BT). The goal of the present study was to investigate the potential effects of glutamine on BT and the immunological response in an experimental model of NO synthase inhibition by NG-nitro-L-arginine methyl ester (l-NAME). Mice were randomly assigned to four groups: sham; intestinal obstruction (IO); IO+500 mg/kg per d glutamine (GLN); IO+GLN plus 10 mg/kg per d l-NAME (GLN/LN). The groups were pretreated for 7 d. BT was induced by ileal ligation and was assessed 18 h later by measuring the radioactivity of 99mTc-Escherichia coli in the blood and organs. Mucosal damage was determined using a histological analysis. Intestinal permeability (IP) was assessed by measuring the levels of 99mTc-diethylenetriaminepentaacetic acid in the blood at 4, 8 and 18 h after surgery. IgA and cytokine concentrations were determined by ELISA in the intestinal fluid and plasma, respectively. BT was increased in the GLN/LN and IO groups than in the GLN and sham groups. IP and intestinal mucosa structure of the sham, GLN and GLN/LN groups were similar. The GLN group had the highest levels of interferon-γ, while IL-10 and secretory IgA levels were higher than those of the IO group but similar to those of the GLN/LN group. The present results suggest that effects of the glutamine pathway on BT were mediated by NO. The latter also interferes with the pro-inflammatory systemic immunological response. On the other hand, IP integrity preserved by the use of glutamine is independent of NO.

Hypertonic saline solution reduces mesenteric microcirculatory dysfunctions and bacterial translocation in a rat model of strangulated small bowel obstruction.

We examined the effects of hypertonic saline (HS) on inflammatory, metabolic variables, and bacterial translocation (BT) in rats submitted to intestinal obstruction and ischemia (IO). Male Wistar rats were submitted to IO and treated, 2 h thereafter, with lactated Ringer's (LR) (4 mL/kg per 5 min, i.v.) or HS (7.5% NaCl, 4 mL/kg per 5 min, i.v.). Twenty-four hours after IO, rats were also submitted to enterectomy/enteroanastomosis to resection of necrotized small bowel. Leukocyte-endothelial interactions were investigated by intravital microscopy and the expression of P-selectin and intercellular adhesion molecule 1 by immunohistochemistry. Bacterial cultures of mesenteric lymph nodes, liver, spleen, and blood were used to evaluate BT. Levels of chemokines (cytokine-induced neutrophil chemoattractants 1 and 2), insulin, and corticosterone were determined by enzyme-linked immunosorbent assay. Intestinal histology, serum urea and creatinine levels, and hepatic enzymes activities were performed to evaluate local and remote damage. Relative to IO and LR-treated rats, which exhibited increases in the number of rolling (1.5-fold), adhered (3.5-fold) and migrated (9.0-fold) leukocytes, and increased expression of P-selectin (3-fold) and intercellular adhesion molecule 1 (3-fold) on mesenteric microcirculation, treatment with HS followed by enterectomy reduced leukocyte-endothelial interactions and expression of both adhesion molecules to values attained in sham rats. Serum chemokines were normalized after treatment with both solutions followed by enterectomy. Hypertonic saline-treated rats demonstrated a significant reduction in BT to 50% in liver and spleen samples and bacteremia (14%), compared with 82% of BT in liver and spleen samples of IO and LR-treated rats and bacteremia (57%). Local intestinal damage was attenuated, and renal and hepatic function preserved by treatment with HS followed by enterectomy. Survival rate increased to 86% up to 15 days. Data presented suggest that HS solution followed by enterectomy reduces mesenteric microcirculatory dysfunctions and BT, attenuating local and remote damage in a model of strangulated small bowel obstruction.

The role of L-arginine and inducible nitric oxide synthase in intestinal permeability and bacterial translocation.

BACKGROUND: Arginine has been shown to have several immunological and trophic properties in stressful diseases. Its metabolites, nitric oxide (NO) and polyamines, are related to arginine's effects. Thus, the aim of this study was to determine the effects of the NO donor L-arginine and the role of inducible NO synthase (iNOS) on intestinal permeability and bacterial translocation in a model of intestinal obstruction (IO) induced by a simple knot in the terminal ileum. MATERIAL AND METHODS: Male C57BL6/J wild-type (WT) and iNOS knockout (iNOS-/-) mice were randomized into 6 groups: Sham and Sham-/- (standard chow), IO and IO-/- (standard chow +IO), and Arg and Arg-/- (standard chow supplemented with arginine + IO). After 7 days of treatment with standard or supplemented chows, IO was induced and intestinal permeability and bacterial translocation were evaluated. The small intestine and its contents were harvested for histopathological and morphometric analysis and the determination of polyamine concentration. RESULTS: Pretreatment with arginine maintained intestinal permeability (P > .05; Arg and Arg-/- groups vs Sham and Sham-/- groups), increased polyamine concentration in intestinal content (P < .05; Arg vs IO group), and decreased bacterial translocation in WT animals (Arg group vs IO and IO-/- groups). Absence of iNOS also presented a protective effect on permeability but not on bacterial translocation. CONCLUSION: Arginine supplementation and synthesis of NO by iNOS are important factors in decreasing bacterial translocation. However, when intestinal permeability was considered, NO had a detrimental role.

Pretreatment with citrulline improves gut barrier after intestinal obstruction in mice.

BACKGROUND: Citrulline has been shown to be an important marker of gut function, regulator of protein metabolism, and precursor of arginine. The authors assessed the effects of citrulline on gut barrier integrity and bacterial translocation (BT) in mice undergoing intestinal obstruction. METHODS: Mice were divided into 3 groups: sham, intestinal obstruction (IO), and citrulline (CIT). The CIT group received a diet containing 0.6% citrulline; the IO and sham groups were fed a standard chow diet. On the eighth day of treatment, all animals received a diethylenetriamine pentaacetic acid (DTPA) solution labeled with (99m)Technetium ((99m)Tc-DTPA) by gavage for the intestinal permeability study. Terminal ileum was ligated except the sham group, which only underwent laparotomy. After 4, 8, and 18 hours, blood was collected to determine radioactivity. Samples of ileum were removed 18 hours after intestinal obstruction for histological analysis. In another set of animals, BT was evaluated. Animals received 10(8) CFU/mL of (99m)Tc-Escherichia coli by gavage; 90 minutes later, they underwent ileum ligation. Intestinal fluid and serum were collected to measure sIgA and cytokines. RESULTS: The CIT group presented decreased intestinal permeability and BT when compared with the IO group (P < .05). Histopathology showed that citrulline preserved the ileum mucosa. The sIgA concentration was higher in the CIT group (P < .05). The IO group presented the highest levels of interferon-γ (P < .05). CONCLUSIONS: Pretreatment with citrulline was able to preserve barrier integrity and also modulated the immune response that might have affected BT decrease.

Lactoferrin increases both resistance to Salmonella typhimurium infection and the production of antibodies in mice.

Lactoferrin (Lf) is a multifunctional iron-binding glycoprotein with antibacterial and immunomodulatory activities. The antibacterial influence of orally administered bovine Lf (bLf) against murine infection caused by Salmonella typhimurium (S. typhimurium) has scarcely been explored. In the current study, Balb/c mice were treated orally for 7 days with either 5 or 100mg of bovine lactoferrin (bLf). On day 7 of treatment, mice were intragastrically infected with a lethal or sublethal dose of colony forming units (CFU) of S. typhimurium. During treatment with bLf, feces from mice sublethally infected were harvested daily to prepare fecal suspensions, which were serially diluted and plated onto Salmonella Shigella agar to estimate CFU/g of feces. After sacrificing the animals on day 7, 14 or 21 post-infection, samples of intestinal fluid, Peyer's patches (PP), liver and spleen were collected to count the number of CFU by plate dilution. Intestinal secretions were also employed, along with serum samples, to evaluate total IgA, IgG and IgM antibodies, and those against Salmonella surface proteins and bLf by ELISA assay. In lethally infected mice both bLf doses decreased mortality. In sublethally infected mice, both bLf doses decreased bacterial shedding in feces and intestinal fluid, and also reduced bacterial colonization at PP and bacterial translocation in the liver and spleen. Levels of total and those IgG and IgM in serum and IgA in intestinal secretions against Salmonella surface proteins and bLf were enhanced with both doses of bLf. These findings suggest that the effect of bLf against the infection by S. typhimurium in mice may be the result of an antimicrobial activity linked with its modulatory effect on immunocompetent cells (from intestinal and peripheral organs) involved in antibody production.

Glutamine supplementation decreases intestinal permeability and preserves gut mucosa integrity in an experimental mouse model.

BACKGROUND: Glutamine (GLN) is the preferred fuel for enterocytes, and GLN supplementation is critical during stressful conditions. The aim of this study was to evaluate the effect of GLN on intestinal barrier permeability and bacterial translocation in a murine experimental model. METHODS: Swiss male mice (25-30 g) were randomized into 3 groups: (1) sham group; (2) intestinal obstruction (IO) group; (3) IO and GLN (500 mg/kg/d) group. Two different experiments were carried out to assess intestinal permeability and bacterial translocation. In the first experiment, the animals were divided into the 3 groups described above and received diethylenetriamine pentaacetate radiolabeled with technetium ((99m)Tc) on the eighth day. At different time points after intestinal obstruction, blood was collected to determine radioactivity. The animals were killed, and the small intestine was removed for histological analyses. In the bacterial translocation study, on the eighth day all groups received Escherichia coli labeled with (99m)Tc. After 90 minutes, the animals underwent intestinal obstruction and were killed 18 hours later. Blood, mesenteric lymph nodes, liver, spleen, and lungs were removed to determine radioactivity. Statistical significance was considered when P < or = .05. RESULTS: The levels of intestinal permeability and bacterial translocation were higher in the IO group than in the sham and GLN groups (P < .05). GLN decreased intestinal permeability and bacterial translocation to physiologic levels in the treated animals and preserved intestinal barrier integrity. CONCLUSIONS: GLN had a positive impact on the intestinal barrier by reducing permeability and bacterial translocation to physiologic levels and preserving mucosal integrity.

Pretreatment with arginine preserves intestinal barrier integrity and reduces bacterial translocation in mice.

OBJECTIVE: To evaluate the effects of arginine on intestinal barrier integrity and bacterial translocation (BT) in mice undergoing intestinal obstruction. METHODS: Mice were divided into 3 groups, treated for 7 d before surgical intervention with isocaloric and isoprotein diets. The ARG group received a diet containing 2% arginine, the IO (intestinal obstruction) and Sham groups, standard chow diet. On the eighth day of treatment, all animals received diethylenetriamine pentaacetic acid (DTPA) solution labeled with 99mTechnetium (99mTc-DTPA) by gavage for intestinal permeability analysis. After 90 min, the animals were anesthetized and the terminal ileum ligated. The Sham group only underwent laparotomy. After 4, 8, and 18 h, blood was collected for radioactivity determination. Samples of ileum were collected 18 h after surgery for histological analysis. In another set of animals, BT was evaluated. After 7 d of treatment, all animals received 10(8) CFU/mL of 99mTc-E.coli by gavage; 90 min later they were submitted to the surgical procedure described above. BT was determined by the uptake of 99mTc-E.coli in blood, mesenteric lymph nodes, liver, spleen, and lungs, assessed 18 h after the surgery. RESULTS: The intestinal permeability and BT were higher in the IO group when compared with the Sham group (P < 0.05). Arginine supplementation reduced intestinal permeability and BT to physiologic levels. Histological analysis showed mucosal ileum preservation in animals treated with arginine. CONCLUSION: Arginine was able to preserve barrier integrity, thus reducing BT.

Bioflora probiotic in immunomodulation and prophylaxis of intestinal bacterial translocation in rats.

UNLABELLED: The immunomodulator effect of Bioflora probiotic on T (CD4+) and B (CD20) lymphocytes in gastrointestinal mucosa and intestinal bacterial translocation was studied using Wistar rats (n = 10 per group). Two experiments were used: (I) stress with immobilization and water immersion at 22 degrees C for 7 h plus the application of indomethacin (Indo) 10 mg/kg SC every 24 h for 3 days (comparator group), and (II) stress experiment I with the addition of 1 mL of Bioflora applied through a orogastric tube every 12 h for 3 days. At the 4th day, in asepsis, a dissection laparotomy of liver, spleen, mesenteric lymphatic nodes, and cecum was performed for microbiological culture, and stomach, ileum, and colon were also dissected for immunohistochemical and quantification of CD4+ and CD20. Findings in experiment I revealed cecum bacterial overdevelopment of 6 x 10(10) +/- 2.3 x 10(9) colony-forming units (CFU) (P < 0.01) and positive cultures in liver, spleen, and all mesenteric lymphatic nodes. On the other hand, in the group treated with Probiotic Bioflora, cecum without overdevelopment (3 x 10(6) +/- 1.3 x 10(5) CFU), negative cultures in liver and spleen, and in lymphatic nodes two positive and eight negative cultures for E. coli and P. vulgaris (P < 0.01) were observed. Immunohistochemistry revealed a relevant increase of T lymphocytes (CD4+) in ileum and colon. CONCLUSIONS: Bioflora probiotic was shown to be an intestinal immunomodulator that induced increased T (CD4+) lymphocytes that also offer prophylaxis of intestinal bacterial translocation in a stressed rat model.

The impact of arginine on bacterial translocation in an intestinal obstruction model in rats.

BACKGROUND & AIMS: Arginine has been shown to have multiple beneficial metabolic and immunologic effects in stress situations. Supplementation of arginine has been shown to promote wound healing and intestinal mucosal recovery after trauma, ischemia or intestinal resection. Bacterial translocation has also been evaluated although with conflicting results and using different assessing techniques. Therefore, the aim of this study was to evaluate the effects of arginine on bacterial translocation in an intestinal obstruction model in rats using Escherichia coli labeled with 99mTechnetium. METHODS: Male Wistar rats (250-350 g) were randomized to receive conventional chow, diet supplemented with pure arginine or diet supplemented with an immunonutrition enteral formula, enriched with arginine, omega-3 fatty acid and RNA. After 7 days, the animals were anesthetized. Terminal ileum was isolated and a ligature was placed around it. E. coli labeled with 99mTechnetium (99mTc-E. coli) was inoculated into the intestinal lumen (terminal ileum). After 24 h, the animals were sacrificed. Blood, mesenteric lymph nodes (MLN), liver, spleen and lungs were removed for radioactivity determination. RESULTS: Arginine supplementation (300 mg/day, 600 mg/day or present in the enteral formula) reduced the level of bacterial translocation when compared with the control group (p<0.05). This was shown by significantly decrease uptake of 99mTc-E. coli in blood, MLN, liver, spleen and lungs of the animals in the experimental groups (p < 0.05). CONCLUSIONS: These results have shown that arginine was able to decrease bacteria translocation despite intestinal obstruction. There are several mechanisms which might explain the role of arginine and these will be the subject of future studies.

Beneficial effect of recombinant human growth hormone on the intestinal mucosa barrier of septic rats.

The objective of the present study was to investigate the effects of recombinant human growth hormone (rhGH) on the intestinal mucosa barrier of septic rats and explore its possible mechanism. Female Sprague-Dawley rats were randomized into three groups: control, Escherichia coli-induced sepsis (S) and treatment (T) groups. Groups S and T were subdivided into subgroups 1d and 3d, respectively. Expression of liver insulin-like growth factor-1 (IGF-1) mRNA, Bcl-2 and Bax protein levels and the intestinal Bax/Bcl-2 ratio, and plasma GH and IGF-1 levels were determined. Histological examination of the intestine was performed and bacterial translocation was determined. rhGH significantly attenuated intestinal mucosal injuries and bacterial translocation in septic rats, markedly decreased Bax protein levels, inhibited the decrease of Bcl-2 protein expression and maintained the Bax/Bcl-2 ratio in the intestine. rhGH given after sepsis significantly improved levels of plasma GH (T1d: 1.28 +/- 0.24; T3d: 2.14 +/- 0.48 microg/L vs S1d: 0.74 +/- 0.12; S3d: 0.60 +/- 0.18 microg/L; P < 0.05) and IGF-1 (T1d: 168.94 +/- 65.67; T3d: 201.56 +/- 64.98 microg/L vs S1d: 116.72 +/- 13.96; S3d: 107.50 +/- 23.53 microg/L; P < 0.05) and expression of liver IGF-1 mRNA (T1d: 0.98 +/- 0.20; T3d: 1.76 +/- 0.17 vs S1d: 0.38 +/- 0.09; S3d: 0.46 +/- 0.10; P < 0.05). These findings indicate that treatment with rhGH had beneficial effects on the maintenance of the integrity of the intestinal mucosa barrier in septic rats.

Beneficial effect of recombinant human growth hormone on the intestinal mucosa barrier of septic rats

The objective of the present study was to investigate the effects of recombinant human growth hormone (rhGH) on the intestinal mucosa barrier of septic rats and explore its possible mechanism. Female Sprague-Dawley rats were randomized into three groups: control, Escherichia coli-induced sepsis (S) and treatment (T) groups. Groups S and T were subdivided into subgroups 1d and 3d, respectively. Expression of liver insulin-like growth factor-1 (IGF-1) mRNA, Bcl-2 and Bax protein levels and the intestinal Bax/Bcl-2 ratio, and plasma GH and IGF-1 levels were determined. Histological examination of the intestine was performed and bacterial translocation was determined. rhGH significantly attenuated intestinal mucosal injuries and bacterial translocation in septic rats, markedly decreased Bax protein levels, inhibited the decrease of Bcl-2 protein expression and maintained the Bax/Bcl-2 ratio in the intestine. rhGH given after sepsis significantly improved levels of plasma GH (T1d: 1.28 ± 0.24; T3d: 2.14 ± 0.48 æg/L vs S1d: 0.74 ± 0.12; S3d: 0.60 ± 0.18 æg/L; P < 0.05) and IGF-1 (T1d: 168.94 ± 65.67; T3d: 201.56 ± 64.98 æg/L vs S1d: 116.72 ± 13.96; S3d: 107.50 ± 23.53 æg/L; P < 0.05) and expression of liver IGF-1 mRNA (T1d: 0.98 ± 0.20; T3d: 1.76 ± 0.17 vs S1d: 0.38 ± 0.09; S3d: 0.46 ± 0.10; P < 0.05). These findings indicate that treatment with rhGH had beneficial effects on the maintenance of the integrity of the intestinal mucosa barrier in septic rats.

Prevention of bacterial translocation using beta-(1-3)-D-glucan in small bowel ischemia and reperfusion in rats.

PURPOSE: To investigate the role of beta-(1-3)-D-glucan on 99mTc labelled Escherichia coli translocation and cytokines secretion in rats submitted to small bowel ischemia/reperfusion injury. METHODS: Five groups (n=10 each) of Wistar rats were subjected to control(C), sham(S), group IR subjected to 45 min of bowel ischemia/60 min of reperfusion(I/R), and group I/R+glucan subjected to 45 min of bowel ischemia/60 min of reperfusion(I/R) and injected with 2 mg/Kg intramuscular. Translocation of labelled bacteria to mesenteric lymph nodes, liver, spleen, lung and serum was determined using radioactivity/count and colony forming units/g(CFU/g). Serum TNFalpha, IL-1beta, IL-6, IL-10 were measured by ELISA. RESULTS: CFU/g and radioactivity/count were higher in I/R than in I/R+glucan rats. In C, S and S+glucan groups, bacteria and radioactivity/count were rarely detected. The I/R+glucan rats had enhancement of IL-10 and suppressed production of serum TNFalpha, IL-1beta and, IL-6, compared to I/R untreated animals. CONCLUSION: The beta-(1-3)-D-glucan modulated the production of pro-inflammatory and anti-inflammatory cytokines during bowel ischemia/reperfusion, and attenuated translocation of labelled bacteria.