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| 1 | Protective effect of glutamine on intestinal injury and bacterial community in rats exposed to hypobaric hypoxia environment显示文摘AIM:To investigate the protective effect of glutamine(Gln)on intestinal injury and the bacterial community in rats exposed to hypobaric hypoxia environment.METHODS:Sprague-Dawley rats were divided into control,hypobaric hypoxia(HH),and hypobaric hypoxia+Gln(5.0 g/kg BW·d)(HG)groups.On the first 3 d,all rats were placed in a normal environment.After the third day,the HH and HG groups were transferred into a hypobaric chamber at a simulated elevation of 7000m for 5 d.The rats in the HG group were given Gln by gavage daily for 8 d.The rats in the control and HH groups were treated with the same volume of saline.The intestinal morphology,serum levels of malondialdehyde(MDA),superoxide dismutase(SOD),interleukin-6 (IL-6),tumor necrosis factor-α(TNF-α),interferon-gamma(IFN-γ)and diamino oxidase(DAO)were examined.We also evaluated the expression levels of occludin,toll-like receptor 4(TLR4),nuclear factor-κB p65(NF-κB p65)and myeloid differentiation factor 88(MyD88),and examined the bacterial community in caecal contents.RESULTS:Hypobaric hypoxia induced the enlargement of the heart,liver,lung and kidney,and caused spleen atrophy.Intestinal villi damage was also observed in the HH group.Supplementation with Gln significantly alleviated hypobaric-induced damage to main organs including the intestine,increased serum SOD(1.14±0.03 vs 0.88±0.04,P<0.05)and MDA(8.35±1.60,P<0.01)levels and decreased serum IL-6(1172.13±30.49 vs 1407.05±34.36,P<0.05),TNF-α(77.46±0.78 vs 123.70±3.03,P<0.001),IFN-γ(1355.42±72.80 vs 1830.16±42.07,P<0.01)and DAO(629.30±9.15 vs 524.10±13.34,P<0.001)levels.Moreover,Gln significantly increased occludin(0.72±0.05 vs 0.09±0.01,P<0.001),TLR4(0.15±0.05 vs 0.30±0.09,P<0.05),MyD88(0.32±0.08 vs 0.71±0.06,P<0.01),and NF-κB p65(0.16±0.04 vs 0.44±0.03,P<0.01)expression levels and improved the intestinal bacterial community.CONCLUSION:Gln treatment protects from intestinal injury and regulates the gut flora imbalance in hypoxia environment.These effects may be related to the TLR4/MyD88/NF-κB signaling pathway. | Chun-Lan Xu Rui Sun Xiang-Jin Qiao Cui-Cui Xu Xiao-Ya Shang Wei-Ning Niu | 2014 | World Journal of Gastroenterology2014，20，16： | 29 |
| 2 | Glutamine:aprecursor of glutathione and its effect on liver显示文摘METHODSTwentymaleWistarratswererandomlydividedintotwogroups:onereceivingstandardparenteralnutrition(STD)andtheothersuppleme... | YU Jian Chun, JIANG Zhu Ming and LI De Min | 1999 | World Journal of Gastroenterology1999，5，2： | 23 |
| 3 | Glutamine synthetase as an early marker for hepatocellular carcinoma based on proteomic analysis of resected smal hepatocel ular carcinomas显示文摘BACKGROUND:Hepatocellular carcinoma(HCC)is a highly malignant tumor with a poor prognosis.Because small HCCs possess most of the characteristics of early HCC,we investigated small HCCs to screen potential biomarkers for early diagnosis.METHODS:Proteins were extracted from 10 sets of paired tissue samples from HBV-infected small-HCC patients.The extracted proteins were well resolved by two-dimensional electrophoresis.These HCC-associated proteins were then identified by MALDI-TOF/TOF MS following image analysis.Western blotting and immunohistochemistry were used to assess glutamine synthetase(GS)and phenazine biosynthesislike domain-containing protein(PBLD)expression in liver tissue.Enzyme-linked immunosorbent assays in 152 serum samples(from 49 healthy donors,24 patients with liver cirrhosis,and 79 with HCC)were used to further assess the significance of GS clinically.RESULTS:Fifteen up-regulated and three down-regulated proteins were identified.Western blotting confirmed GS overexpression and decreased PBLD expression in liver tissue.Immunohistochemistry showed that GS was expressed in 70.0%(84/120)of HCCs and 35.8%(43/120)of nontumor tissues;PBLD was expressed in 74.2%(89/120) of nontumor tissues and 40.8%(49/120)of HCCs.The Chi-square test showed significant expression differences between HCCs and adjacent tissues.Consistent with this,serum GS levels in HCC patients were significantly higher than those in liver cirrhosis patients and healthy donors,while the latter two groups were also significantly different.In addition, a diagnostic cutoff value of 2.6 mg/ml was used for GS;it was elevated in 19(76.0%)of 25 HCC patients with AFP≤20 ng/ml and 47(88.7%)of 53 HCC patients with AFP≤200 ng/ml.CONCLUSION:GS and PBLD are abnormally expressed in most HCCs.GS may be a novel serum marker for early HCC, especially for those patients with low AFP levels(≤200 ng/ml). | Jiang Long,Zhen-Wei Lang,Hua-Guang Wang,Tai-Ling Wang,Bao-En Wang and Si-Qi Liu Liver Research Center,Beijing Friendship Hospital, Capital Medical University,Beijing 100050,China Department of Hepatology,Department of Pathology, Beijing Youan Hospital,Capital Medical University,Beijing 100069,China Department of Pharmaceutical Affairs,Beijing Chaoyang Hospital,Capital Medical University,Beijing 100020,China Department of Pathology,China-Japan Friendship Hospital,Beijing 100029,China Beijing Genomics Institute,Chinese Academy of Science,Beijing Airport Industrial Zone B-6,Shunyi,Beijing 101300,China | 2010 | Hepatobiliary & Pancreatic Diseases International2010，9，3： | 21 |
| 4 | Effect of bowel rehabilitative therapy on structural adaptation of remnant small intestine: animal experiment显示文摘AIM To investigate the individual and thecombined effects of glutamine, dietary fiber,and growth hormone on the structural adaptationof the remnant small bowel.METHODS Forty-two adult male Sprague-Dawley rats underwent 85% mid-small bowel( TPN ) support during the first threepostoperational days. From the 4thpostoperational day, animals were randomlyassigned to receive 7 different treatments for 8days: TPNcon group, receiving TPN and enteral20 g.L- 1 glycine perfusion; TPN + Gin group,receiving TPN and enteral 20 g.L-1 glutamineperfusion; ENcon group, receiving enteralnutrition (EN) fortified with 20 g@L-1 glycine; EN+ Gin group, enteral nutrition fortified with20g. L-1 glutamine; EN + Fib group, enteralnutrition and 2 g. d- 1 oral soybean fiber; EN + GHgroup, enteral nutrition and subcutaneousgrowth hormone (GH) (0.31U) injection twicedaily; and ENint group, glutamine-enriched EN.oral soybean fiber, and subcutaneous GHinjection.RESULTS Enteral glutamine perfusion duringTPN increased the small intestinal villus height(jejunal villus height 250 μm ±29 μm in TPNconvs 330 μm ± 54 μm in TPN + Gin, ileal villus height260μm±28μm in TPNcon vs 330 μm±22μm inTPN + Gin, P<0.05) and mucosa thickness( jejunal mucosa thickness 360 μm ± 32 μm inTPNcon vs 460 μm ± 65 μm in TPN + Gin, ilealmucosa thickness 400 μm ± 25 μm in TPNcon vs490μm ± 11 μm in TPN + Gin, P<0.05) incomparison with the TPNcon group. Either fibersupplementation or GH administration improvedbody mass gain (end body weight 270 g ± 3.6 g inEN+Fib, 265.7 g ± 3.3 g in EN+GH, vs 257g±3.3g in ENcon, P<0.05), elevated plasmainsulin-like growth factor ( IGF-Ⅰ ) level(880 μg. L-1 ± 52 μg. L-1 in EN + Fib, 1200 μg. L-1± 96 μg. L- 1 in EN ± GH, vs 620 μg. L-1 ±43 μg. L-1 in ENcon, P<0.05), and increased thevillus height (jejunum 560 μm ± 44 μm in EN ± Fib,530 μm± 30 μm in EN ± GH, vs 450 μm ± 44 μm inENcon, ileum 400 μm ± 30 μm in EN + Fib, 380 μm±49 μm in EN± GH, vs 320 μm± 16 μm in ENcon,P<0.05) and the mucosa thickness (jejunum740 μm ± 66 μm in EN ± Fib, 705 μm ± 27 μm in EN ±GH, vs 608 μm ± 58 μm in ENcon, ileum 570 μm ±27 μm in EN ± Fib, 560 μm ± 56 μm in EN ± GH, vs480μm ± 40 μm in ENcon, P<0.05) in remnantjejunum and ileum. Glutamine-enriched ENproduced little effect in body mass, plasma IGF-Ⅰ level, and remnant small bowel mucosalstructure. The ENint group had greater bodymass (280g ± 2.2g), plasma IGF-Ⅰ level(1450g@L-1 ± 137g. L 1), and villus height(jejunum 620 μm ± 56 μm, ileum 450 um ± 31 μm)and mucosal thickness (jejunum 800 μm ± 52 μm,ileum 633 μm± 33 μm) than those in ENcon, EN +Gin (jejunum villus height and mucosa thickness450 μm ± 47 μm and 610 μm ± 63 μm, ileum villusheight and mucosa thickness 330 μm ± 39 μm and500 μm± 52 μm), EN + GH groups (P<0.05), andthan those in EN + Fib group although nostatistical significance was attained.CONCLUSION Both dietary fiber and GH whenused separately can enhance the postresectionalsmall bowel structural adaptation. Simultaneoususe of these two gut-trophic factors can producesynergistic effects on small bowel structuraladaptation. Enteral glutamine perfusion isbeneficial in preserving small bowel mucosalstructure during TPN, but has little beneficialeffect during EN. | Xin Zhou1 Yuan Xin Li2 Ning Li2 Jie Shou Li2 1Department of General Surgery, Medical School, Nanjing University, Nanjing 210093. Jiangsu Province. China2Research Institute of General Hospital. Chinese PLA General Hospital of Nanjing Military Area, Nanjing 210002. Jiangsu Province. China | 2001 | World Journal of Gastroenterology2001，7，1： | 14 |
| 5 | Arginine, N-carbamylglutamate,and glutamine exert protective effects against oxidative stress in rat intestine显示文摘The objective of the current study is to evaluate the effects of dietary supplementation with arginine(ARG), N-carbamylglutamate(NCG), and glutamine(GLN) on rat intestinal morphology and antioxidant status under oxidative stress. Rats were fed for 30 d with one of the following iso-nitrogenous diets:basal diet(BD), BD plus 1% ARG, BD plus 0.1% NCG, and BD plus 1% GLN. On day 28, half of the rats fed BD were intraperitoneally injected with 12 mg/kg body weight of diquat(DT; i.e., the DT group) and the other half was intraperitoneally injected with sterile solution(i,e., the control group). The other diet groups were intraperitoneally injected with 12 mg/kg body weight of DT(i,e., DT + 1% GLN [DT + GLN],DT + 1% ARG [DT + ARG], and DT + 0.1% NCG [DT + NCG]). Rat jejunum samples obtained at 48 h after DT injection were analyzed. Results showed that DT significantly decreased catalase(CAT) activity and glutathione(GSH) content by 58.25% and 56.57%, respectively, and elevated malondialdehyde(MDA)content and crypt depth(CD) by 19.39% and 22.13%, respectively, in the jejunum(P < 0.05, relative to the control group). Compared with the DT group, the DT + GLN group exhibited significantly improved villus height(VH), villus width(VW), villus surface area(VSA), CD and total antioxidant capacity(T-AOC) activity(P < 0.05); the DT + ARG group exhibited significantly increased the ratio of VH to CD(H:D) and TAOC activity(P < 0.05); the DT + GLN, DT + ARG and DT + NCG groups exhibited significantly enhanced CAT activity and GSH content as well as decreased MDA content(P < 0.05). Moreover, VH, VW, VSA, CD and GSH content in the DT + GLN group were higher whereas MDA content was lower compared with the corresponding values observed in both the DT + ARG and the DT + NCG groups(P < 0.05). The H:D ratio in the DT + ARG group significantly increased compared with that in the DT + NCG and DT + GLN groups(P < 0.05). Collectively, this study suggested that dietary supplementation with 1% GLN, 0.1% NCG,and 1% ARG was effective in enhancing the antioxidant status and maintaining the morphological structure of rat jejunum under oxidative stress; of these supplements, 1% GLN exerted the greatest effects on mitigating oxidative stress. | Liang Xiao Wei Cao Guangmang Liu Tingting Fang Xianjian Wu Gang Jia Xiaoling Chen Hua Zhao Jing Wang Caimei Wu Jingyi Cai | 2016 | Animal Nutrition2016，，3： | 12 |
| 6 | Antioxidant properties of glutamine and its role in VEGF-Akt pathways in portal hypertension gastropathy显示文摘AIM: To investigate the effects of glutamine on oxidative/nitrosative stress and the vascular endothelial growth factor (VEGF)-Akt-endothelial nitric oxide synthase (eNOS) signaling pathway in an experimental model of portal hypertension induced by partial portal vein ligation (PPVL). METHODS: Portal hypertension was induced by PPVL. The PPVL model consists of a partial obstruction of the portal vein, performed using a 20 G blunt needle as a guide, which is gently removed after the procedure. PPVL model was performed for 14 d beginning treatment with glutamine on the seventh day. On the fifteenth day, the mesenteric vein pressure was checked and the stomach was removed to test immunoreactivity and oxidative stress markers. We evaluated the expression and the immunoreactivity of proteins involved in the VEGF-Akt-eNOS pathway by Western blotting and immunohistochemical analysis. Oxidative stress was measured by quantification of the cytosolic concentration of thiobarbituric acid reactive substances (TBARS) as well as the levels of total glutathione (GSH), superoxide dismutase (SOD) activity, nitric oxide (NO) production and nitrotyrosine immunoreactivity. RESULTS: All data are presented as the mean ± SE. The production of TBARS and NO was significantly increased in PPVL animals. A reduction of SOD activity was detected in PPVL + G group. In the immunohistochemical analyses of nitrotyrosine, Akt and eNOS, the PPVL group exhibited significant increases, whereas decreases were observed in the PPVL + G group, but no difference in VEGF was detected between these groups. Western blotting analysis detected increased expression of phosphatidylinositol-3-kinase (PI3K), P-Akt and eNOS in the PPVL group compared with the PPVL + G group, which was not observed for the expression of VEGF when comparing these groups. Glutamine administration markedly alleviated oxidative/nitrosative stress, normalized SOD activity, increased levels of total GSH and blocked NO overproduction as well as the formation of peroxynitrite. CONCLUSION: Glutamine treatment demonstrated to reduce oxidative damage but does not reduce angiogenesis induced by PH in gastric tissue, demonstrating a beneficial role for the PI3K-Akt-eNOS pathway. | Camila Marques Francielli Licks Ingrid Zattoni Beatriz Borges Luiz Eduardo Rizzo de Souza Claudio Augusto Marroni Norma Possa Marroni | 2013 | World Journal of Gastroenterology2013，19，28： | 9 |
| 7 | Enteral nutrition combined with glutamine promotes recovery after ileal pouch-anal anastomosis in rats显示文摘AIM To assess the effect of enteral nutrition(EN) supplemented with glutamine on recovery after ileal pouch-anal anastomosis(IPAA) in rats, to provide an experimental basis for nutritional support in patients with ulcerative colitis(UC) after IPAA. METHODS Male Sprague-Dawley(SD) rats were randomly divided into three groups(n = 8) after IPAA operation using a microsurgical technique. From the third postoperative day, rats in the control group, EN group, and immune nutrition(IN) group were fed standard rat chow, short peptide EN, and short peptide EN combined with glutamine ad libitum, respectively. The rats' general condition was observed throughout the study. Serum levels of total protein(TP), albumin(ALB), prealbumin(PA), and transferrin(TF) were detected on the 30 th postoperative day, using an automatic biochemical analyzer. The ileal pouch mucosa was stained with hematoxylin and eosin(HE), and occludin protein levels were detected by immunohistochemistry.RESULTS The body weight of rats in the EN group(359.20 ± 10.06 g) was significantly higher than that in the control group(344.00 ± 9.66 g)(P < 0.05) and lower than that in the IN group(373.60 ± 9.86 g)(P < 0.05) on the 30 th postoperative day. The levels of serum TP, ALB, PA, and TF in the EN group were significantly higher than those in the control group(P < 0.01 for all) and lower than those in the IN group(P < 0.05 for all). Histopathological score(EN: 0.80 ± 0.37; IN: 0.60 ± 0.40; control group: 2.29 ± 0.18) and expression level of occludin protein(EN: 0.182 ± 0.054; IN: 0.188 ± 0.048; control group: 0.127 ± 0.032) were significantly lower in the control group compared with the EN and IN groups(P < 0.05 for all), but there were no significant differences between the latter two groups(P > 0.05 for all). CONCLUSION EN combined with glutamine may effectively improve nutritional status after IPAA. Our results suggest a benefit of glutamine supplementation in EN for UC patients undergoing IPAA, although human studies are required to confirm this finding. | Yan-Yan Xu An-Qi He Gang Liu Kai-Yu Li Jian Liu Tong Liu | 2018 | World Journal of Gastroenterology2018，24，5： | 9 |
| 8 | Co-suppressed glutamine synthetase2 gene modifies nitrogen metabolism and plant growth in rice显示文摘A full-length cDNA that encodes the rice chloroplastic glutamine synthetase 2 gene was isolated from a Minghui 63-normalized cDNA library; and GS2 rice transformants were obtained by an Agrobacterium tumefaciens-mediated transformation method. Transcripts of the GS2 gene were shown to accumulate at higher levels in the primary transgenic plants in the T0 generation; whereas plants in the T1 generation exhibited a co-suppressed chlorosis phenotype (yellow leaves) accompanied by decreased plant height, few tillers and decreased dry weight. The plants with yellow leaves also displayed a significant decline in GS2 messenger RNA (mRNA) transcriptional level and chlorophyll content; a decrease in total GS activities of ~50% was also found. Although there was no decrease in the concentration of total free amino acids, a change in the concentration of individual amino acids was observed. Our result also indicates a decreased metabolic level (soluble protein content and ammonium concentration) in GS2 co-suppressed plants. A correlation between chlorophyll content and GS2 mRNA expression level was also observed. The GS2 co-suppressed plants showed better performance when complemented with exogenous glutamine, indicating that the lack of an organic nitrogen pool inside the cell is the possible reason for the chlorosis phenotype of the transformants. | CAI HongMei XIAO JingHua ZHANG QiFa LIAN XingMing | 2010 | Chinese Science Bulletin2010，55，9： | 8 |
| 9 | Glutamine prevents oxidative stress in a model of mesenteric ischemia and reperfusion显示文摘AIM: To evaluate preventative effects of glutamine in an animal model of gut ischemia/reperfusion(I/R).METHODS: Male Wistar rats were housed in a controlled environment and allowed access to food and water ad libitum. Twenty male Wistar rats were divided into four experimental groups:(1) control group(control)- rats underwent exploratory laparotomy;(2) control + glutamine group(control-GLU)- rats were subjected to laparotomy and treated intraperitoneally with glutamine 24 and 48 h prior to surgery;(3) I/R group- rats were subjected to occlusion of the superior mesenteric artery for 30 min followed by 15 min of reperfusion; and(4) ischemia/reperfusion + glutamine group(G + I/R)- rats were treated intraperitoneally with glutamine 24 and 48 h before I/R. Local and systemic injuries were determined by evaluating intestinal and lung segments for oxidative stress using lipid peroxidation and the activity of superoxide dismutase(SOD), interleukin-6(IL-6) and nuclear factor kappa beta(NFkB) after mesenteric I/R. RESULTS: Lipid peroxidation of the membrane was increased in the animals subjected to I/R(P < 0.05). However, the group that received glutamine 24 and 48 h before the I/R procedure showed levels of lipid peroxidation similar to the control groups(P < 0.05). The activity of the antioxidant enzyme SOD was decreased in the gut of animals subjected to I/R when compared with the control group of animals not subjected to I/R(P < 0.05). However, the group that received glutamine 24 and 48 h before I/R showed similar SOD activity to both control groups not subjected to I/R(P < 0.05). The mean area of NF-kB staining for each of the control groups was similar. The I/R group showed the largest area of staining for NF-kB. The G + I/R group had the second highest amount of staining, but the mean value was much lower than that of the I/R group(P < 0.05). For IL-6, control and control-GLU groups showed similar areas of staining. The I/R group contained the largest area of IL-6 staining, followed by the G + I/R animals; however, this area was significantly lower than that of the group that underwent I/R without glutamine(P < 0.05). CONCLUSION: These results demonstrate that pretreatment with glutamine prevents mucosal injury and improves gut and lung recovery after I/R injury in rats. | Gilmara Pandolfo Zabot Gustavo Franco Carvalhal Norma Possa Marroni Renata Minuzzo Hartmann Vinícius Duval da Silva Henrique Sarubbi Fillmann | 2014 | World Journal of Gastroenterology2014，20，32： | 7 |
| 10 | Molecular mechanisms of protein induced hyperinsulinaemic hypoglycaemia显示文摘The interplay between glucose metabolism and that of the two other primary nutrient classes, amino acids and fatty acids is critical for regulated insulin secretion. Mitochondrial metabolism of glucose, amino acid and fatty acids generates metabolic coupling factors(such as ATP, NADPH, glutamate, long chain acyl-CoA and diacylglycerol) which trigger insulin secretion. The observation of protein induced hypoglycaemia in patients with mutations in GLUD1 gene, encoding the enzyme glutamate dehydrogenase(GDH) and HADH gene, encoding for the enzyme short-chain 3-hydroxyacyl-CoA dehydrogenase has provided new mechanistic insights into the regulation of insulin secretion by amino acid and fatty acid metabolism. Metabolic signals arising from amino acid and fatty acid metabolism converge on the enzyme GDH which integrates both signals from both pathways and controls insulin secretion. Hence GDH seems to play a pivotal role in regulating both amino acid and fatty acid metabolism. | Suresh Chandran Fabian Yap Khalid Hussain | 2014 | World Journal of Diabetes2014，5，5： | 6 |
| 11 | Glutamine transporters as pharmacological targets: From function to drug design显示文摘Among the different targets of administered drugs,there are membrane transporters that play also a role in drug delivery and disposition.Moreover,drug-transporter interactions are responsible for off-target effects of drugs underlying their toxicity.The improvement of the drug design process is subjected to the identification of those membrane transporters mostly relevant for drug absorption,delivery and side effect production.A peculiar group of proteins with great relevance to pharmacology is constituted by the membrane transporters responsible for managing glutamine traffic in different body districts.The interest around glutamine metabolism lies in its physio-pathological role;glutamine is considered a conditionally essential amino acid because highly proliferative cells have an increased request of glutamine that cannot be satisfied only by endogenous synthesis.Then,glutamine transporters provide cells with this special nutrient.Among the glutamine transporters,SLC1A5,SLC6A14,SLC6A19,SLC7A5,SLC7A8 and some members of SLC38 family are the best characterized,so far,in both physiological and pathological conditions.Few 3D structures have been solved by CryoEM;other structural data on these transporters have been obtained by computational analysis.Interactions with drugs have been described for several transporters of this group.For some of them,the studies are at an advanced stage,for others,the studies are still in nuce and novel biochemical findings open intriguing perspectives. | Mariafrancesca Scalise Lorena Pochini Michele Galluccio Lara Console Cesare Indiveri | 2020 | Asian Journal of Pharmaceutical Sciences2020，15，2： | 5 |
| 12 | Levels of Metabolic Enzymes and Nitrogenous Compounds in the Swimming Crab Portunus trituberculatus Exposed to Elevated Ambient Ammonia-N显示文摘This study investigated the effects of ammonia-N(control and 1 and 5 mg L^(-1)) on the changes of metabolic enzymes activities and nitrogenous compounds levels in the gills, hepatopancreas, muscles, and hemolymph of the swimming crab Portunus trituberculatus. Results showed that the levels of hemolymph ammonia increased significantly at 6 h and then decreased to control level at 12 h. The activities of key enzymes involved in biosynthesis pathways of glutamine(Gln) and urea, such as glutamate dehydrogenase(GDH), glutamine synthetase(GS), and arginase(ARG), increased remarkably in different tissues of P. trituberculatus. Gln level was the highest in muscles, while urea content was the largest in hepatopancreas. The m RNA expression level of xanthine dehydrogenase(XDH) was downregulated sharply in gills but upregulated in the hepatopancreas and muscles. A small amount of uric acid was detected in the hemolymph. This result suggests that Gln in muscles may be used as an intermediary nitrogen repository, while urea may be primarily synthesized in the hepatopancreas and then transferred to other tissues via the hemolymph. Uric acid could be synthesized by the anabolism of purine nucleotides, in additon to the inhibitory activities of gills. In addition, the levels of Gln, urea and uric acid exhibited dose-and time-dependent effects with ammonia content. Therefore, P. trituberculatus could possibly convert ammonia into Gln, urea, or uric acid to detoxify ammonia during high ambient ammonia-N stress. | PAN Luqing SI Lingjun LIU Shengnan LIU Maoqi WANG Guohui | 2018 | Journal of Ocean University of China2018，17，4： | 5 |
| 13 | Effects of glutamine and curcumin on bacterial translocation in jaundiced rats显示文摘AIM: To investigate the effect of curcumin on bacterial translocation and oxidative damage in an obstructive jaundice model and compare the results to glutamine, an agent known to be effective and clinically used. METHODS: Twenty-four female Wistar-Albino rats, weighing 200-250 g, were randomly divided into three groups (8 in each group). After ligation of the common bile duct in all animals, GroupⅠ received oral normal saline, Group Ⅱ received oral glutamine and Group Ⅲ received oral curcumin for seven days. Blood samples via cardiac puncture, tissue samples (terminal ileum, liver and mesenteric lymph node) and peritoneal fluid were obtained from the animals at the time of death to investigate bacterial translocation and oxidative damage. RESULTS: We observed that both glutamine and curcumin reduced bacterial translocation in blood, hepatocellular damage, plasma cytokine levels, oxidative tissue damage and apoptosis significantly compared to the control group. Additionally, glutamine showed protective effects on ileal epithelium and reduced villus atrophy. CONCLUSION: On the basis of these findings, both curcumin and glutamine are thought to be effective in preventing or reducing bacterial translocation and oxidative damage in obstructive jaundice. | Oguzhan Karatepe Ersin Acet Muharrem Battal Gokhan Adas Ahu Kemik Merih Altiok Gulcin Kamali Safiye Koculu Atahan Catay Sedat Kamali Servet Karahan | 2010 | World Journal of Gastroenterology2010，16，34： | 5 |
| 14 | Protective action of glutamine in rats with severe acute liver failure显示文摘BACKGROUND Severe acute liver failure(SALF) is a rare, but high-mortality, rapidly evolving syndrome that leads to hepatocyte degeneration with impaired liver function.Thioacetamide(TAA) is a known xenobiotic, which promotes the increase of the formation of reactive oxygen species. Erythroid 2-related factor 2(Nrf2) activates the antioxidant protection of cells. Studies have evidenced the involvement of inflammatory mediators in conditions of oxidative stress.AIM To evaluate the antioxidant effects of glutamine on Nrf2 activation and NFκBmediated inflammation in rats with TAA-induced IHAG.METHODS Male Wistar rats(n = 28) were divided into four groups: control,control+glutamine, TAA, and TAA + glutamine. Two TAA doses(400 mg/kg)were administered intraperitoneally, 8 h apart. Glutamine(25 mg/kg) was administered at 30 min, 24 h, and 36 h. At 48 h, blood was collected for liver integrity analysis [aspartate aminotransferase(AST), alanine aminotransferase(ALT), and alkaline phosphatase(ALP)]. The liver was harvested for histology and assessment of oxidative stress [thiobarbituric acid-reactive substances(TBARS), catalase(CAT), glutathione peroxidase(GPx), glutathione S-transferase(GST), glutathione(GSH), Nrf2, Kelch-like ECH-associated protein 1(Keap1),NADPH quinone oxidoreductase1(NQO1), superoxide dismutase(SOD)] and inflammatory process.RESULTS TAA caused disruption of the hepatic parenchyma, with inflammatoryinfiltration, massive necrosis, and ballooning degeneration. Glutamine mitigated this tissue damage, with visible regeneration of hepatic parenchyma; decreased TBARS(P < 0.001), GSH(P < 0.01), IL-1β, IL6, and TNFα levels(P <0.01) in hepatic tissue; and decreased blood levels of AST, ALT, and ALP(P <0.05). In addition, CAT, GPx, and GST activities were restored in the glutamine group(P<0.01, P <0.01, and P <0.001, respectively vs TAA alone). Glutamine increased expression of Nrf2(P < 0.05), NQO1, and SOD(P < 0.01), as well as levels of IL-10(P <0.001), while decreasing expression of Keap1, TLR4, NFκB(P < 0.001), COX-2 and iNOS,(P < 0.01), and reducing NO_2 and NO_3 levels(P < 0.05).CONCLUSION In the TAA experimental model of IHAG, glutamine activated the Nrf2 pathway,thus promoting antioxidant protection, and blunted the NFκB-mediated pathway, reducing inflammation. | Elizangela G Schemitt Renata M Hartmann Josieli R Colares Francielli Licks Jéferson O Salvi Cláudio A Marroni Norma P Marroni | 2019 | World Journal of Hepatology2019，11，3： | 5 |
| 15 | Glutamine and glutamate: Nonessential or essential amino acids?显示文摘Glutamine and glutamate are not considered essential amino acids but they play important roles in maintaining growth and health in both neonates and adults. Although glutamine and glutamate are highly abundant in most feedstuffs there is increasing evidence that they may be limiting during pregnancy, lactation and neonatal growth, particularly when relatively low protein diets are fed. Supplementation of diets with glutamine, glutamate or both at 0.5 to 1.0% to both suckling and recently weaned piglets improves intestinal and immune function and results in better growth. In addition such supplementation to the sow prevents some of the loss of lean body mass during lactation, and increases milk glutamine content. However, a number of important questions related to physiological condition,species under study and the form and amount of the supplements need to be addressed before the full benefits of glutamine and glutamate supplementation in domestic animal production can be realized. | Malcolm Watford | 2015 | Animal Nutrition2015，，3： | 5 |
| 16 | Systematic analyses of glutamine and glutamate metabolisms across different cancer types显示文摘Background: Glutamine and glutamate are known to play important roles in cancer biology. However, no detailed information is available in terms of their levels of involvement in various biological processes across different cancer types, whereas such knowledge could be critical for understanding the distinct characteristics of different cancer types. Our computational study aimed to examine the functional roles of glutamine and glutamate across different cancer types.Methods: We conducted a comparative analysis of gene expression data of cancer tissues versus normal control tissues of 11 cancer types to understand glutamine and glutamate metabolisms in cancer. Specifically, we developed a linear regression model to assess differential contributions by glutamine and/or glutamate to each of seven biological processes in cancer versus control tissues.Results: While our computational predictions were consistent with some of the previous observations, multiple novel predictions were made:(1) glutamine is generally not involved in purine synthesis in cancer except for breast cancer, and is similarly not involved in pyridine synthesis except for kidney cancer;(2) glutamine is generally not involved in ATP production in cancer;(3) glutamine's contribution to nucleotide synthesis is minimal if any in cancer;(4) glutamine is not involved in asparagine synthesis in cancer except for bladder and lung cancers; and(5) glutamate does not contribute to serine synthesis except for bladder cancer.Conclusions: We comprehensively predicted the roles of glutamine and glutamate metabolisms in selected metabolic pathways in cancer tissues versus control tissues, which may lead to novel approaches to therapeutic development targeted at glutamine and/or glutamate metabolism. However, our predictions need further functional validation. | Yuan Tian Wei Du Sha Cao Yue Wu Ning Dong Yan Wang Ying Xu | 2017 | Chinese Journal of Cancer2017，36，12： | 5 |
| 17 | Protective effects of glutamine preconditioning on ischemia-reperfusion injury in rats显示文摘BACKGROUND:Hepatic ischemia-reperfusion injury is a common phenomenon in hepatic surgical procedures and can result in further severe damage.This study aimed to investigate the protective effects of glutamine preconditioning on hepatic ischemia-reperfusion injury in rats and its dose-dependency. METHODS:Thirty-two healthy male Wistar rats were randomly divided into four groups(n=8 per group).One group received 0.9%NaCl(control)and the other three received glutamine(Gln groups)4 hours before ischemia.The Gln groups were named GL,GM,and GH according to the glutamine dose.The liver was subjected to 1 hour of ischemia and 2 hours of reperfusion. Two hours later,the levels of alanine aminotransferase(ALT), intracellular free calcium(Ca 2+ ),and activity of Na + /K + adenosine triphosphatase(ATPase)and superoxide dismutase (SOD)were assessed,and liver tissue sections were examined under a microscope. RESULTS:The Gln and control groups differed in the concentration of intracellular free calcium(P<0.05),and the activity of Na + /K + ATPase and SOD in the Gln groups was higher than in the control group(P<0.05).The ALT level was lower in the GM and GH groups than in the control group(P<0.05).The levels of Na + /K + ATPase and SOD rose gradually with increasing glutamine dose(P<0.05),and the concentration of Ca 2+ declined gradually with increasing glutamine dose(P<0.05).The degree of hepatocyte injury was milder in the Gln groups than in the control group. CONCLUSIONS:Glutamine preconditioning protected effectively against hepatic ischemia-reperfusion injury.These protective effects were related to the dose of glutamine and due to the reduction of intracellular calcium overload and the improvements in the activity of Na + /K + ATPase and SOD. | Wan-Xing Zhang,Li-Fang Zhou,Lei Zhang,Lei Bao,Chun-ChengWang,Hui-Yan Meng and WenYin Department of Hepatobiliary Surgery,and Department of Pharmacy ,Hebei Provincial General Hospital,Shijiazhuang 050051,China | 2011 | Hepatobiliary & Pancreatic Diseases International2011，10，1： | 5 |
| 18 | Changes of Levels of Glutamine Synthetase Isoforms in Roots and Leaves in Responseto Nitrogen Fertilizer Application at Different Growth Stages in Irrigated Rice显示文摘Nitrogen is a key element to control the growth and yield of crops. Fertilizer urea nitrogen(N)60,45,and 30 kg/hm2 was applied at three different stages, midtillering, panicle initiation, and flowering,of the growth and development of rice plants. respectively. At both midtillering and panicle initiation, the total activity of glutamine synthetase (GS) in rice roots and leaves ovas increased remarkably as a result of a large amount of ammonia absorbed by roots. Native-PAGE and activity staining showed that the increase of total activity in rice roots and leaves was due to the synthesis of GSrb in roots and GSZ in leaves and that the activity of GSra in roots and GSI in leaves remained constant. The results shoaled that the assimilation of external nitrogen was carried out by GSrb but not GSra in rice roots and that the activitry. of GS2 ovas induced also by the external nitrogen, and that GSrb played main role in meeting the needs of the rapid tillering for nitrogen. At flowering, the activity of GS in rice roots and leaves did not change almost after topdressing.These rssults suggest that the change of GS activity in rice roots may use as a measure of the utilization efficiency of the fertilizer. | Zhang Chufu Peng Shaobing John Bennett | 1998 | Wuhan University Journal of Natural Sciences1998，3，4： | 4 |
| 19 | 1H nuclear magnetic resonance spectroscopy-basedmetabonomic study in patients with cirrhosis and hepaticencephalopathy显示文摘AIM: To identify plasma metabolites used as biomarkers in order to distinguish cirrhotics from controls and encephalopathics.METHODS: A clinical study involving stable cirrhotic patients with and without overt hepatic encephalopathy was designed. A control group of healthy volunteers was used. Plasma from those patients was analysed using 1H- nuclear magnetic resonance spectroscopy. We used the Carr Purcell Meiboom Gill sequence to process the sample spectra at ambient probe temperature. We used a gated secondary irradiation field for water signal suppression. Samples were calibrated and referenced using the sodium trimethyl silyl propionate peak at 0.00 ppm. For each sample 128 transients(FID's) were acquired into 32 K complex data points over a spectral width of 6 KHz. 30 degree pulses were applied with an acquisition time of 4.0 s in order to achieve better resolution, followed by a recovery delay of 12 s, to allow for complete relaxation and recovery of the magnetisation. A metabolic profile was created for stable cirrhotic patients without signs of overt hepatic encephalopathy and encephalopathic patients as well as healthy controls. Stepwise discriminant analysis was then used and discriminant factors were created to differentiate between the three groups.RESULTS: Eighteen stabled cirrhotic patients, eighteen patients with overt hepatic encephalopathy and seventeen healthy volunteers were recruited. Patients with cirrhosis had significantly impaired ketone body metabolism, urea synthesis and gluconeogenesis. This was demonstrated by higher concentrations of acetoacetate(0.23 ± 0.02 vs 0.05 ± 0.00, P < 0.01), and b-hydroxybutarate(0.58 ± 0.14 vs 0.08 ± 0.00, P < 0.01), lower concentrations of glutamine(0.44 ± 0.08 vs 0.63 ± 0.03, P < 0.05), histidine(0.16 ± 0.01 vs 0.36 ± 0.04, P < 0.01) and arginine(0.08 ± 0.01 vs 0.14 ± 0.02, P < 0.03) and higher concentrations of glutamate(1.36 ± 0.25 vs 0.58 ± 0.04, P < 0.01), lactate(1.53 ± 0.11 vs 0.42 ± 0.05, P < 0.01), pyruvate(0.11 ± 0.02 vs 0.03 ± 0.00, P < 0.01) threonine(0.39 ± 0.02 vs 0.08 ± 0.01, P < 0.01) and aspartate(0.37 ± 0.03 vs 0.03 ± 0.01). A five metabolite signature by stepwise discriminant analysis could separate between controls and cirrhotic patients with an accuracy of 98%. In patients with encephalopathy we observed further derangement of ketone body metabolism, impaired production of glycerol and myoinositol, reversal of Fischer's ratio and impaired glutamine production as demonstrated by lower b-hydroxybutyrate(0.58 ± 0.14 vs 0.16 ± 0.02, P < 0.0002), higher acetoacetate(0.23 ± 0.02 vs 0.41 ± 0.16, P < 0.05), leucine(0.33 ± 0.02 vs 0.49 ± 0.05, P < 0.005) and isoleucine(0.12 ± 0.02 vs 0.27 ± 0.02, P < 0.0004) and lower glutamine(0.44 ± 0.08 vs 0.36 ± 0.04, P < 0.013), glycerol(0.53 ± 0.03 vs 0.19 ± 0.02, P < 0.000) and myoinositol(0.36 ± 0.04 vs 0.18 ± 0.02, P < 0.010) concentrations. A four metabolite signature by stepwise discriminant analysis could separate between encephalopathic and cirrhotic patients with an accuracy of 87%.CONCLUSION: Patients with cirrhosis and patients with hepatic encephalopathy exhibit distinct metabolic abnormalities and the use of metabonomics can select biomarkers for these diseases. | Konstantinos John Dabos John Andrew Parkinson Ian Howard Sadler John Nicholas Plevris Peter Clive Hayes | 2015 | World Journal of Hepatology2015，7，12： | 3 |
| 20 | Intravenous glutamine for severe acute pancreatitis:A meta-analysis显示文摘AIM: To evaluate the efficacy of intravenous glutamine on the patients with severe acute pancreatitis(SAP).METHODS: The Cochrane Library, Pub Med, EMBASE, and EBM review databases were searched up to June 2012. Randomized controlled trials(RCTs) that compared non-glutamine nutrition with intravenous glutamine supplemented nutrition in patients with SAP were included. A method recommended by the Cochrane Collaboration was used to perform a meta-analysis of those RCTs. RESULTS: Four RCTs involving a total of 190 participants were included. Analysis of these RCTs revealed the presence of statistical homogeneity among them. Results showed that glutamine dipeptide has a positive effect in reducing the mortality rate(OR = 0.26, 95%CI: 0.09-0.73, P = 0.01), length of hospital stay(weighted mean difference =-4.85, 95%CI: 6.67--3.03, P < 0.001), and the rate of complications(OR = 0.41, 95%CI: 0.22-0.78, P = 0.006). No serious adverse effects were found.CONCLUSION: Current best evidence demonstrates that glutamine is effective for SAP. Further high quality trials are required and parameters of nutritional condition and hospital cost should be considered in future RCTs with sufficient size and rigorous design. | Xin Zhong Cui-Ping Liang Shu Gong | 2013 | World Journal of Critical Care Medicine2013，2，1： | 3 |
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