Protective Effect Of Glutamine Research Articles

Glutamine-mediated Modulation of XO/uric acid/NF-kB Signaling Pathway Ameliorates Intestinal I/R-induced Bacterial Translocation and Cardiorenal Inflammatory Injury.

This study explored the effect of intestinal ischaemia/reperfusion (I/R) on cardiorenal tissues. The involvement of xanthine oxidase/uric acid/NF-kB signaling in intestinal I/R was also investigated. In addition, the possible protective effect of glutamine was also evaluated. Twenty-four male Wistar rats were acclimatized and then randomly assigned to four groups (n = 6); sham-operated, glutamine-treated rats (GLUT), I/R, and I/R + GLUT. The sham-operated rats were sham-operated and received 0.5 mL of distilled water, GLUT rats were sham-operated and had 1 g/kg b.w. of glutamine, I/R animals had an intestinal I/R procedure and received 0.5 mL of distilled water, and the I/R + GLUT rats had an intestinal I/R procedure and also received 1 g/kg b.w. of glutamine. Treatments were daily and per os. Glutamine attenuated intestinal I/R-induced rise in intestinal and cardiorenal activities of creatinine kinase and lactate dehydrogenase and lactate level. More so, glutamine alleviated I/R-induced rise in malondialdehyde, xanthine oxidase, uric acid, myeloperoxidase, NF-kB, TNF-α, IL-1β, caspase 3 activity, and DNA fragmentation. Furthermore, glutamine suppressed I/R-induced decline in GSH levels and SOD and catalase activities. Moreover, glutamine improved intestinal, cardiac, and renal histology in animals subjected to intestinal I/R.

The protective effects of glutamine against bronchopulmonary dysplasia are associated with MKP-1/MAPK/cPLA2 signalingmediated NF-kappaB pathway.

Glutamine is proven to have potential therapeutic effects on decreasing hyperoxia-induced acute pulmonary injury. The aim of this study is to investigate the effects and mechanism of glutamine on bronchopulmonary dysplasia (BPD) induced by hyperoxia in rat alveolar type II epithelial cells (AECIIs) RLE-6TN. Following hyperoxia induction and glutamine treatment, ROS levels were detected by DCFH-DA assay and TUNEL staining was performed to detect cell apoptosis. The levels of inflammatory indicators and expression of apoptosis-related proteins were detected through ELISA and Western blot, respectively. Besides, the expression of related proteins in mitogen-activated protein kinase phosphatase-1 (MKP-1)/mitogen-activated protein kinases (MAPK)/cytoplasmic phospholipase A2 (cPLA2) signaling was also detected by Western blot. To further analyze the role of MKP-1/MAPK/cPLA2 signaling, MKP-1 was silenced and anisomycin was used to treat cells, respectively. It was shown that glutamine significantly decreased inflammation, oxidative stress and apoptosis in hyperoxia-induced cells while MKP-1 interference and anisomycin were able to reverse these effects, suggesting that the protective effects of glutamine on BPD induced by hypoxia were related to MKP-1/MAPK/cPLA2 signaling. To sum up, glutamine protected against BPD by decreasing inflammation, oxidative stress and apoptosis via MKP-1/MAPK/cPLA2 signaling.

Protective effects of glutamine on lipopolysaccharide/D-galactosamine-induced fulminant hepatitis in mice.

Fulminant hepatitis remains a critical health problem owing to its high mortality rate and the lack of effective therapies. An increasing number of studies have shown that glutamine supplementation provides protective benefits in inflammation-related disorders, but the pharmacological significance of glutamine in lipopolysaccharide (LPS)/D-galactosamine (D-Gal)-induced fulminant hepatitis remains unclear. In the present study, the potential effects of glutamine on LPS/D-Gal-induced fulminant hepatitis were investigated. Pretreatment with glutamine decreased plasma activities of alanine and aspartate aminotransferases, and ameliorated hepatic morphological abnormalities in LPS/D-Gal-exposed mice. Glutamine pretreatment also inhibited LPS/D-Gal-induced tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) production. In addition, glutamine pretreatment decreased the level of cleaved cysteinyl aspartate-specific proteinase 3 (caspase-3), suppressed the activities of caspase-3, caspase-8, and caspase-9, and reduced the number of cells positive for TdT-mediated dUTP nick-end labeling in LPS/D-Gal-challenged mice. Interestingly, post-treatment with glutamine also provided protective benefits against LPS/D-Gal-induced acute liver injury, although these effects were less robust than those of glutamine pre-treatment. Thus, glutamine may have potential value as a pharmacological intervention in fulminant hepatitis.

Protective Effects of Glutamine and Leucine Supplementation on Sepsis-Induced Skeletal Muscle Injuries.

This study investigated the effects of l-glutamine (Gln) and/or l-leucine (Leu) administration on sepsis-induced skeletal muscle injuries. C57BL/6J mice were subjected to cecal ligation and puncture to induce polymicrobial sepsis and then given an intraperitoneal injection of Gln, Leu, or Gln plus Leu beginning at 1 h after the operation with re-injections every 24 h. All mice were sacrificed on either day 1 or day 4 after the operation. Blood and muscles were collected for analysis of inflammation and oxidative damage-related biomolecules. Results indicated that both Gln and Leu supplementation alleviated sepsis-induced skeletal muscle damage by reducing monocyte infiltration, calpain activity, and mRNA expression levels of inflammatory cytokines and hypoxia-inducible factor-1α. Furthermore, septic mice treated with Gln had higher percentages of blood anti-inflammatory monocytes and muscle M2 macrophages, whereas Leu treatment enhanced the muscle expressions of mitochondrion-related genes. However, there were no synergistic effects when Gln and Leu were simultaneously administered. These findings suggest that both Gln and Leu had prominent abilities to attenuate inflammation and degradation of skeletal muscles in the early and/or late phases of sepsis. Moreover, Gln promoted the switch of leukocytes toward an anti-inflammatory phenotype, while Leu treatment maintained muscle bioenergetic function.

Protective effect of glutamine and alanyl-glutamine against zearalenone-induced intestinal epithelial barrier dysfunction in IPEC-J2 cells

Zearalenone (ZEN), a nonsteroidal estrogenic mycotoxin, has a negative effect on porcine intestine. Glutamine (Gln) and alanyl-glutamine (Ala-Gln) are nutrients with potential preservation functions similar to those of the intestinal epithelial barrier. The protective role of Gln and Ala-Gln on ZEN-induced intestinal barrier dysfunction was evaluated in this study. Additionally, the ability of Gln and Ala-Gln to protect the intestinal barrier was investigated. Our results showed that lactate dehydrogenase (LDH) activity, paracellular permeability and reactive oxygen species (ROS) level were increased by ZEN, while the glutathione (GSH) level was decreased by ZEN. Gln and Ala-Gln promoted the proliferation of cells and attenuated the ZEN-induced increase in cytotoxicity, cell apoptosis and paracellular permeability. Gln and Ala-Gln alleviated barrier function damage, which was additionally induced by ZEN by increasing the antioxidant capacity of cells. In addition, Gln and Ala-Gln upregulated intestinal barrier associated gene expressions including pBD-1, pBD-2, MUC-2, ZO-1, occludin and claudin-3. This study revealed that Gln and Ala-Gln had similar effects in protecting intestinal epithelial barrier function against ZEN exposure in IPEC-J2 cells. A new treatment for alleviating ZEN-induced injury to the intestine through nutritional intervention is provided.

Protective effects of glutamine against soy saponins-induced enteritis, tight junction disruption, oxidative damage and autophagy in the intestine of Scophthalmus maximus L

Soy saponins, as thermo-stable anti-nutrients in soybean meal (SBM), are the primary causal agents of SBM-induced enteritis, which represents a well-documented pathologic alternation involving the distal intestines of various farmed fish. Our previous work showed that soy saponins might lead to SBM-induced enteritis, destroy tight junction structure and induce oxidative damage in juvenile turbot. Glutamine, as a conditionally essential amino acid, is an important substrate utilized for the growth of intestinal epithelial cells. An 8-week feeding trial was carried out to determine whether glutamine can attenuate the detrimental effects of soy saponins. Three isonitrogenous-isolipidic experimental diets were formulated as follows: (i) fish meal-based diet (FM), considered as control; (ii) FM + 10 g/kg soy saponins, SAP; and (iii) SAP + 15 g/kg glutamine, GLN. The results showed that dietary soy saponins significantly increased the gene expression levels of inflammatory markers (IL-1β, IL-8 and TNF-α) and related signaling factors (NF-кB, AP-1, p38, JNK and ERK), which were remarkably attenuated by dietary glutamine. Compared to SAP group, GLN-fed fish exhibited significantly higher expression levels of tight junction genes (CLDN3, CLDN4, OCLN, Tricellulin and ZO-1). Glutamine supplementation in SAP diet markedly suppressed the production of reactive oxygen species, malondialdehyde and protein carbonyl, and enhanced the activities of antioxidant enzymes as well as the mRNA levels of HO-1, SOD, GPX and Nrf2. Furthermore, GLN-fed fish had a remarkably lower number of autophagosomes compared to SAP-fed fish. In conclusion, our study indicated that glutamine could reverse the harmful effects of soy saponins on intestinal inflammation, tight junction disruption and oxidative damage, via attenuation of NF-кB, AP-1 and MAPK pathways and activation of Nrf2 pathway. Glutamine may have the function of controlling autophaghic process within an appropriate level of encountering inflammation.

The protective effect of L-glutamine against acute Cantharidin-induced Cardiotoxicity in the mice

BackgroundCantharidin (CTD) is a compound which have the potential to be exploited as an antitumor drug, and it has been demonstrated antitumor effects in a variety of cancers. However, the use is limited due to its severe toxicity. It has reported that it can induce fatal cardiac arrhythmias. Fortunately, we found that L-glutamine can alleviate cardiac toxicity caused by cantharidin in mice.MethodsTo investigate the protective effect of L-glutamine, we used a high dose of cantharidin in mice to create a model of cardiotoxicity. In the experimental mice, glutamine was given orally half an hour before they were administrated with cantharidin. The mice of control group were intraperitoneally injected with DMSO solution. The general state of all mice, cardiac mass index, electrocardiogram change and biological markers were determined. Hematoxylin-eosin staining (HE staining) of heart tissue was carried out in each group to reflect the protective effect of glutamine. To investigate the mechanisms underlying the injury and cardio-protection, multiple oxidative stress indexes were determined and succinate dehydrogenase activity was evaluated.ResultThe results showed that L-glutamine (Gln) pretreatment reduced weight loss and mortality. It also decreased the biological markers (p < 0.05), improved electrocardiogram and histological changes that CTD induced cardiotoxicity in mice. Subsequently, the group pretreated with L-glutamine before CTD treatment increases in MDA but decreases in SOD and GSH, in comparison to the group treated with CTD alone. Besides, succinate dehydrogenase activity also was improved when L-glutamine was administrated before cantharidin compared to cantharidin.ConclusionsThis study provided evidence that L-glutamine could protect cardiac cells against the acute cantharidin-induced cardiotoxicity and the protective mechanism of glutamine may be related to the myocardial cell membrane or the tricarboxylic acid cycle in the mitochondria.

Protective effect of glutamine and arginine against soybean meal-induced enteritis in the juvenile turbot (Scophthalmus maximus)

Soybean meal can induce enteritis in the distal intestine (DI) and decrease the immunity of several cultured fish species, including turbot Scophthalmus maximus. Glutamine and arginine supplementation have been used to improve immunity and intestinal morphology in fish. This study was conducted to investigate the effects of these two amino acids on the immunity and intestinal health of turbot suffering from soybean meal-induced enteritis. Turbots (initial weight 7.6 g) were fed one of three isonitrogenous and isolipidic diets for 8 weeks: SBM (control diet), with 40% soybean meal; GLN, SBM diet plus 1.5% glutamine; ARG, the SBM diet plus 1.5% arginine. Symptoms that are typical of soybean meal-induced enteritis, including swelling of the lamina propria and subepithelial mucosa and a strong infiltration of various inflammatory cells was observed in fish that fed the SBM diet. Glutamine and arginine supplementation significantly increased (1) the weight gain and feed efficiency ratio; (2) the height and vacuolization of villi and the integrity of microvilli in DI; (3) serum lysozyme activity, and the concentrations of C3, C4, and IgM. These two amino acids also significantly decreased the infiltration of leucocytes in the lamina propria and submucosa and the expression of inflammatory cytokines including il-8, tnf-α, and tgf-β. For the mucosal microbiota, arginine supplementation significantly increased microbiota community richness and diversity, and glutamine supplementation significantly increased the relative abundance of Lactobacillus and Bacillus. These results indicate that dietary glutamine and arginine improved the growth performance, feed utilization, and distal intestinal morphology, activated the innate and adaptive immune systems, changed the intestinal mucosal microbiota community, and relieved SBMIE possibly by suppression of the inflammation response.

Effects Of Oral Glutamine on Inflammatory and Autophagy Responses in Cancer Patients Treated With Abdominal Radiotherapy: A Pilot Randomized Trial.

Background and Aims: Abdominal radiotherapy (RT) causes harm to the mid gastrointestinal mucosa by release of pro-inflammatory cytokines and promotes autophagic changes in tumor cells. This study was aimed to measure the effect of glutamine administration on markers of inflammation and autophagy in cancer patients treated with RT.Methods: In this double-blind, randomized, controlled pilot trial 43 patients under abdominal RT diagnosed of pelvic or abdominal malignancies receiving glutamine (30 g/d) or placebo (casein, 30 g/d). Patient recruitment took place in the Complejo Asistencial Universitario of León (CAULE), Spain. Patient evaluation took place at three different time points during the study: before RT (pre-treatment), in the middle of the RT period (mid-treatment), and after finishing RT (post-treatment). Data were compared by analysis of variance and the Newmann Keuls test. Significance was accepted at p < 0.05.Results Abdominal RT increased whole blood mRNA levels of inflammatory and autophagic markers, but glutamine administration showed significantly lower expression of toll-like receptor 4 (TLR4), CD36, interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX-2), and matrix metalloproteinase-9 (MMP-9). Moreover, glutamine reduced the expression of the transcription factors nuclear factor kappa B (NF-κB) and activator protein 1 (AP-1). Glutamine also inhibited the autophagic response, with changes in expression of beclin-1, UV radiation resistance associated gene (UVRAG), autophagy-related protein-5 (Atg5), protein 1 light chain 3 (LC3), sequestosome 1 (p62/SQSTM1) and lysosome-associated membrane protein (LAMP)-1.Conclusions Findings provide evidence that glutamine decreases the inflammatory response and abolishes the changes of the autophagy machinery in patients receiving abdominal RT. The protective effect of glutamine must continue being investigated to disclose further molecular pathways.

The protective effects of glutamine in a rat model of ventilator-induced lung injury.

The mortality rate of patients with acute respiratory distress syndrome (ARDS) is still high despite the use of protective ventilatory strategies. We sought to examine the pharmacological effects of glutamine (GLN) in a two-hit model of endotoxin-induced inflammation followed by ventilator-induced lung injury (VILI). We hypothesized that the administration of GLN ameliorates the VILI. Sprague-Dawley rats were anesthetized and given lipopolysaccharide (LPS) intratracheally as a first hit to induce lung inflammation, followed 24 h later by a second hit of mechanical ventilation (MV) with either low tidal volume (6 mL/kg) with 5 cmH2O of positive end-expiratory pressure (PEEP) or high tidal volume (22 mL/kg) with zero PEEP for 4 h. GLN or lactated Ringer's solution as the placebo was administered intravenously 15 min prior to MV. In the LPS-challenged rats ventilated with high tidal volume, the treatment with GLN improved lung injury indices, lung mechanics and cytokine responses compared with the placebo group. The administration of GLN given immediately prior to MV may be beneficial in the context of reducing VILI.

Prevention of Late PJI

The definition of late PJI is variable in literature. Majority of the members of the consensus felt that any infection occurring after one year should be considered as late. Coventry defined stages of PJI, where Stage I is an acute infection that occurred within 3 months of the index procedure, Stage II is a delayed infection that occurred between 3 months and 2 years after the index procedure where there was no pain-free interval, and Stage III is a hematogenous infection where there is a pain-free stage [1]. Garvin and Hanssen defined a late chronic PJI as one that occurred 4 weeks after the index procedure with an insidious clinical onset [2]. McPherson et al defined a chronic infection as one that had symptoms for 4 weeks or longer [3]. In Sweden, a late PJI is defined as one that occurs 2 years after the index procedure. Due to the huge variation in time frames, we did not find consensus in defining a timeframe for a late PJI. However, we classified late PJI as late hematogenous PJI, where there was an asymptomatic period followed by clinical and/or radiographical signs of infection. The workgroup feels that late PJI arises as a result of bacteremia at a later stage [4] and should be distinguished with infections arising as a result of intraoperative contamination. Risk factors for late PJI are similar to those described for PJI in Workgroup 1 (Please see Question 1, Workgroup 1).

Glutamine and arginine improve permeability and tight junction protein expression in methotrexate-treated Caco-2 cells

Chemotherapy induces an increase of intestinal permeability that is partially related to an alteration of tight junction proteins, occludin and zonula occludens-1 (ZO-1). Protective effects of glutamine on intestinal barrier function have been previously shown but the effects of other amino acids remained poorly documented. Thus, we aimed to evaluate the effects of nine amino acids on intestinal permeability during methotrexate (MTX) treatment in Caco-2 cells. Caco-2 cells were incubated in culture medium supplemented with glutamine, arginine, glutamate, leucine, taurine, citrulline, glycine, histidine or cysteine during 24h and then treated with MTX (100ng/ml). The dose of each amino acid was 16.6 fold the physiological plasma concentrations. Barrier function was assessed by transepithelial electrical resistance (TEER), FITC-dextran paracellular flux, occludin and ZO-1 expression and localization. Signaling pathways were also studied. Only glutamine, glutamate, arginine and leucine reversed the decrease of TEER observed after MTX treatment (P<0.05). Interestingly, the addition of 6-diazo-5-oxo-1-norleucine, an inhibitor of glutaminase, blunted the effect of glutamine on MTX-treated cells (P<0.05). Glutamine and arginine combination restored TEER and FITC-dextran flux to a similar extent than glutamine alone. In addition, pretreatment of Caco-2 cells with glutamine and arginine, alone or combined, differently limited the decrease of ZO-1 and occludin expression (P<0.05) and the alteration of their cellular distribution, through c-Jun N-terminal kinase (JNK), Extracellular signal-regulated kinase (ERK) and nuclear factor kappa B (NF-κB) pathways. Glutamine prevented MTX-induced barrier disruption in Caco-2 cells. Arginine also had protective effects but in a lesser extent. The effect of glutamine and arginine should be evaluated invivo.

Protective effects of l-glutamine on the bladder wall of rats submitted to pelvic radiation

Radiotherapy is often used to treat prostate tumors, but the normal bladder is usually adversely affected. Using an animal model of pelvic radiation, we investigated whether glutamine nutritional supplementation can prevent radiation-induced damage to the bladder, especially in its more superficial layers. Male rats aged 3–4 months were divided into groups of 8 animals each: controls, which consisted intact animals; radiated-only rats, which were sacrificed 7 (R7) or 15 (R15) days after a radiation session (10Gy aimed at the pelvico-abdominal region); and radiated rats receiving l-glutamine supplementation (0.65g/kg body weight/day), which were sacrificed 7 (RG7) or 15 (RG15) days after the radiation session. Cells and blood vessels in the vesical lamina propria, as well as the urothelium, were then measured using histological methods. The effects of radiation were evaluated by comparing controls vs. either R7 or R15, while a protective effect of glutamine was assessed by comparing R7 vs. RG7 and R15 vs. RG15. The results showed that, in R7, epithelial thickness, epithelial cell density, and cell density in the lamina propria were not significantly affected. However, density of blood vessels in R7 was reduced by 48% (p<0.05) and this alteration was mostly prevented by glutamine (p<0.02). In R15, density of blood vessels in the lamina propria was not significantly modified. However, epithelial thickness was reduced by 25% (p<0.05) in R15, and this effect was prevented by glutamine (p<0.01). In R15, epithelial cell density was increased by 35% (p<0.02), but glutamine did not protect against this radiation-induced increase. Cell density in the lamina propria was likewise unaffected in R15. Density of mast cells in the lamina propria was markedly reduced in R7 and R15. The density was still reduced in RG7, but a higher density in RG15 suggested a glutamine-mediated recovery. Alpha-actin positive cells in the lamina propria formed a suburothelial layer and were identified as myofibroblasts. Thickness of this layer was increased in R7, but was similar to controls in RG7, while changes in R15 and RG15 were less evident. In conclusion, pelvic radiation leads to significant acute and post-acute alterations in the composition and structural features of the vesical lamina propria and epithelium. Most of these changes, however, can be prevented by glutamine nutritional supplementation. These results emphasize, therefore, the potential use of this aminoacid as a radioprotective drug.

Protective effect of glutamine in critical patients with acute liver injury.

Glutamine (Gln) supplementation is known to decrease oxidative stress and inflammatory response, enhance resistance to infectious pathogens, shorten hospital stay, and decrease medical costs of patients. This study was undertaken to evaluate the relationship between the effect of early parenteral glutamine (Gln) supplement on acute liver injury (ALI) and heat shock protein 70 (HSP-70) expression in critical patients. Forty-four patients who had been admitted to the emergency intensive care unit (EICU) of Nanjing First Hospital Affiliated to Nanjing Medical University were randomly divided into a control group (n=22) and a Gln group (n=22). The patients of the two groups received enteral and parenteral nutrition. In addition, parenteral Gln 0.4 g/kg per day was given for 7 days in the Gln group. Serum HSP-70 and Gln were measured at admission and at 7 days after admission. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBiL), serum levels of HSP-70 and Gln, mechanical ventilation (MV) time, ICU stay, peripheral blood of TNF-α, IL-6, CD3, CD4 and CD4/CD8 levels were also measured in the two groups. In the Gln group, the levels of serum HSP-70 and Gln were significantly higher after Gln treatment than those before the treatment (P<0.01). HSP-70 level was positively correlated with the Gln level in the Gln group after administration of parenteral Gln (P<0.01). The levels of serum ALT, AST, TBiL and TNF-α, IL-6 were lower in the Gln group than in the non-Gln group (P<0.01). MV time and ICU stay were significantly different between the two groups (P<0.05). The levels of CD3, CD4 and CD4/CD8 were significantly higher in the Gln group than in the control group after treatment (P<0.05). Parenteral Gln significantly increases the level of serum HSP70 in critically ill patients. The enhanced expression of HSP70 is correlated with improved outcomes of Gln-treated patients with acute liver injury.

Glutamine protects against apoptosis via downregulation of Sp3 in intestinal epithelial cells

Glutamine plays a key role in intestinal growth and maintenance of gut function, and as we have shown protects the postischemic gut (Kozar RA, Scultz SG, Bick RJ, Poindexter BJ, Desoigne R, Weisbrodt NW, Haber MM, Moore FA. Shock 21: 433-437, 2004). However, the precise mechanisms of the gut protective effects of glutamine have not been well elucidated. In the present study, RNA microarray was performed to obtain differentially expressed genes in intestinal epithelial IEC-6 cells following either 2 mM or 10 mM glutamine. The result demonstrated that specificity protein 3 (Sp3) mRNA expression was downregulated 3.1-fold. PCR and Western blot confirmed that Sp3 expression was decreased by glutamine in a time- and dose-dependent fashion. To investigate the role of Sp3, Sp3 gene siRNA silencing was performed and apoptosis was assessed. Silencing of Sp3 demonstrated a significant increase in Bcl-2 and decrease in Bax protein expression, as well as a decrease in caspase-3, -8, and -9 protein expression and activity. The protein expression of apoptosis-related proteins after hypoxia/reoxygenation was similar to that of normoxia and correlated with a decrease in DNA fragmentation. Importantly, the addition of glutamine to Sp3-silenced cells did not further lessen apoptosis, suggesting that Sp3 plays a major role in the inhibitory effect of glutamine on apoptosis. This novel finding may explain in part the gut-protective effects of glutamine.

Progress in protective effects of glutamine on intestine

谷氨酰胺(Gln)是人体内含量最多的条件必需氨基酸,是一种高效能量物质,为体内合成嘌呤、嘧啶及核苷酸提供氮的前体,参与体内酸碱平衡调节,运送氮源和氮源的提供者,是肠道黏膜细胞及各种快速生长细胞的代谢氧化燃料.与肝脏或骨骼肌相比,小肠上皮细胞内Gln池贮量很小,明显依赖于外源性Gln的供给,小肠黏膜Gln合成酶活性也很低.因此,早产儿有必要补充Gln.在应激状态下,Gln通过降低肠黏膜通透性、增强肠道免疫力、阻止肠黏膜细胞凋亡和减少菌群移位等作用保护肠道.早产儿经胃肠道或静脉补充Gln能改善喂养耐受性,缩短静脉营养时间,并能更快过渡到全胃肠道喂养,还能降低坏死性小肠结肠炎的发生率.但目前临床上是否对重症患者和早产儿等常规使用Gln还存在很大争议,Gln的用量也还没有明确的标准可供参考。

Changes in expressions of the myocardial Toll-like receptor 4, tumor necrosis factor-alpha and interleukin-6 mRNA in rat with sepsis

To investigate the relationship between apoptosis of myocardial cell in the rats with sepsis and the expressions of Toll-like receptor 4 (TLR4), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) mRNA, and the protective effect of glutamine (Gln) against apoptosis of myocardial cell. Rat model of sepsis was reproduced by peritoneal injection with lipopolysaccharide (LPS), and the animals were divided into control group, LPS group and Gln group. Rats in each group were further divided into four subgroups, 0, 6, 12 and 24 hours ( n =6). Apoptosis of myocardial cells was surveyed, and TLR4, TNF-alpha and IL-6 mRNA expressions were assessed with reverse transcription-polymerase chain reaction (RT-PCR). The pathological changes in myocardial cells were observed. Myocardial apoptosis rate in LPS group was higher. Compared with the control group, expressions of TLR4 mRNA, TNF-alpha mRNA and IL-6 mRNA were significantly higher at all time points after LPS administration in the LPS group and the Gln group (all P<0.05). Compared with the LPS group, the rate of myocardial apoptosis in Gln group was lower, and expression of TLR4 mRNA in the Gln group was significantly lower at 12 hours and 24 hours; the expression of TNF-alpha mRNA was obviously lower at 6 hours and 24 hours; the expression of IL-6 mRNA in the Gln group was significantly lower at 12 hours (all P<0.05). TLR4, TNF-alpha and IL-6 gene expressions play extremely important role in apoptosis of myocardial cell in the rat with sepsis. Gln can affect apoptosis-related gene expressions, thus alleviating the apoptosis of myocardial cell.

Glutamine attenuates lipopolysaccharide-induced acute lung injury

Objectives It has been reported that glutamine (GLN) can attenuate acute lung injury after sepsis. GLN is also thought to be a precursor of glutathione (GSH) synthesis. Using the GSH synthesis blocker, L-buthionine-(S,R)-sulfoximine (BSO), we investigated the role of GSH synthesis in the protective effect of GLN on acute lung injury. Methods In this study, we used an acute lung injury model induced by intratracheal injection of lipopolysaccharide (1 mg · mL −1 · kg −1). GLN (0.75 g/kg, intravenous) and BSO (2 mmol/kg, intraperitoneal) were administrated simultaneously. At 2 and 18 h after the injections, the rats were sacrificed by right ventricular puncture and bronchoalveolar lavage was done. The lower right lung was excised for histologic examination. Total protein concentration and total cell and neutrophil counts in the bronchoalveolar lavage fluid were determined. CD11b expression in the blood was determined by flow cytometry. We also analyzed myeloperoxidase activity, and GSH and interleukin-8 levels in lung tissues. Results GLN supplementation reduced the total protein concentration and total cell and neutrophils counts in bronchoalveolar lavage fluid after lipopolysaccharide challenge. GLN enhanced GSH synthesis and attenuated interleukin-8 release and myeloperoxidase activity in lung tissues. GLN also decreased CD11b expression in blood neutrophils and prevented lung histologic changes. BSO abolished the effects of GLN and attenuated its protection on acute lung injury. Conclusion These results indicate that GLN could prevent neutrophil recruitment and infiltration, protect the alveolar barrier, and attenuate inflammatory injury during sepsis. This effect may be related to enhanced GSH synthesis.

Intravenous glutamine decreases lung and distal organ injury in an experimental model of abdominal sepsis

IntroductionThe protective effect of glutamine, as a pharmacological agent against lung injury, has been reported in experimental sepsis; however, its efficacy at improving oxygenation and lung mechanics, attenuating diaphragm and distal organ injury has to be better elucidated. In the present study, we tested the hypothesis that a single early intravenous dose of glutamine was associated not only with the improvement of lung morpho-function, but also the reduction of the inflammatory process and epithelial cell apoptosis in kidney, liver, and intestine villi.MethodsSeventy-two Wistar rats were randomly assigned into four groups. Sepsis was induced by cecal ligation and puncture surgery (CLP), while a sham operated group was used as control (C). One hour after surgery, C and CLP groups were further randomized into subgroups receiving intravenous saline (1 ml, SAL) or glutamine (0.75 g/kg, Gln). At 48 hours, animals were anesthetized, and the following parameters were measured: arterial oxygenation, pulmonary mechanics, and diaphragm, lung, kidney, liver, and small intestine villi histology. At 18 and 48 hours, Cytokine-Induced Neutrophil Chemoattractant (CINC)-1, interleukin (IL)-6 and 10 were quantified in bronchoalveolar and peritoneal lavage fluids (BALF and PLF, respectively).ResultsCLP induced: a) deterioration of lung mechanics and gas exchange; b) ultrastructural changes of lung parenchyma and diaphragm; and c) lung and distal organ epithelial cell apoptosis. Glutamine improved survival rate, oxygenation and lung mechanics, minimized pulmonary and diaphragmatic changes, attenuating lung and distal organ epithelial cell apoptosis. Glutamine increased IL-10 in peritoneal lavage fluid at 18 hours and bronchoalveolar lavage fluid at 48 hours, but decreased CINC-1 and IL-6 in BALF and PLF only at 18 hours.ConclusionsIn an experimental model of abdominal sepsis, a single intravenous dose of glutamine administered after sepsis induction may modulate the inflammatory process reducing not only the risk of lung injury, but also distal organ impairment. These results suggest that intravenous glutamine may be a potentially beneficial therapy for abdominal sepsis.

Antioxidant defense of glutamine on myocardial antioxidant status in adriamycin-induced cardiomyopathy in rats

Oxidative stress is one of the major factors involved in the pathogenesis of adriamycin-induced cardiac dysfunction. The present study examined the antioxidant defense of glutamine on myocardial antioxidant status in adriamycin-induced cardiomyopathy in rats with respect to changes in the levels of lipid peroxidation and reduced glutathione, and the activities of antiperoxidative enzymes [superoxide dismutase (SOD) and catalase (CAT)] and glutathione dependent antioxidant enzymes [glutathione peroxidase (GPx) and glutathione-S-transferase (GST)] in the heart tissue. Intraperitoneal injection of adriamycin caused a significant (P<0.001) rise in the level of lipid peroxidation in the heart tissue with a concomitant (P<0.001) decline in the level of reduced glutathione and the activities of the antioxidant enzymes. Oral administration of glutamine significantly (P<0.001) ameliorated these adriamycin induced adverse effects and maintained the level of the evaluated parameters nearly at normal. The results of the present investigation demonstrated that the protective effects of glutamine against the toxicity of the prooxidant antitumor drug, adriamycin, might be attributed at least partially to its antioxidant properties.