Low-protein diet supplemented with 1% L-glutamine improves growth performance,serum biochemistry,redox status,plasma amino acids,and alters fecal microbiota in weaned piglets

Glutamine,one of the most abundant amino acids in the body,has been shown to exert various beneficial effects in pigs.However,knowledge regarding the role of dietary glutamine in low-protein diet-fed piglets remains scarce.The present study aimed to investigate the effects of different levels of L-gluta-mine on growth performance,serum biochemistry parameters,redox status,amino acids,and fecal microbiota in low-protein diet-fed piglets.A total of 128 healthy crossbred piglets(Landrace x Yorkshire)were randomly allocated into 4 groups of 4 replicate pens,with 8 piglets per pen.Piglets in the 4 groups were fed with corn and soybean meal-based low-protein diets(crude protein level,17%)that contained 0%,1%,2%,and 3%L-glutamine,respectively,for 28 d.Pigs administered 1%L-glutamine had greater body weight on d 28 and average daily gain(ADG,P<0.01),whereas a lower feed to gain ratio(F:G)from d 1 to 28(P<0.01),compared to the other three groups.Besides,lower body weight on d 14 and 28,ADG,average daily feed intake,and higher F:G from d 15 to 28 and d 1 to 28 were observed in response to 2%and 3%L-glutamine treatments than 0%and 1%L-glutamine treatments(P<0.01).Moreover,1%L-glutamine reduced serum glucose,malondialdehyde,hydrogen peroxide concentrations and inhibited aspartate aminotransferase,alanine aminotransferase,myeloperoxidase activities in low-protein diet-fed piglets on d 14,with concomitantly upregulated catalase,total superoxide dismutase activities and glutathione level(P<0.05).However,dietary 3%L-glutamine enhanced blood urea nitrogen content in pigs on d 14(P<0.05).Further investigation revealed that 1%L-glutamine upregulated the serum glutamine,lysine,methionine,tyrosine,and reduced plasma valine content(P<0.05).Additionally,1%L-glutamine upregulated the abundance of p_75_a5,Clostridium,Lactobacillus,Prevotellaceae_Prevotella,and Gemmiger in the stool of piglets on d 14,with the Streptococcus level being concomitantly reduced(P<0.05).Collectively,dietary 1%L-glutamine enhances the growth performance and improves serum physiochemical parameters and antioxidative capacity in low-protein diet-fed piglets at an early age,which are associated with an increased synthesis of glutathione by modulating amino acid levels,and the optimization of gut microbiota.

Environmental enrichment in combination with Bifidobacterium breve HNXY26M4 intervention amplifies neuroprotective benefits in a mouse model of Alzheimer's disease by modulating glutamine metabolism of the gut microbiome

The gut microbiota-brain axis has emerged as a novel target for Alzheimer's disease(AD),a neurodegenerative disease characterised by behavioural and cognitive impairment.However,most previous microbiome-based intervention studies have focused on single factors and yielded only modest cognitive improvements.Here,we proposed a multidomain intervention strategy that combined Bifidobacterium breve treatment with environmental enrichment(EE)training.In this study,we found that compared with EE or B.breve treatment alone,B.breve intervention combined with EE amplified its neuroprotective effects on AD mice,as reflected by improved cognition,inhibited neuroinflammation and enhanced synaptic function.Moreover,using microbiome and metabolome profiling,we found that the combination of B.breve and EE treatment restored AD-related gut microbiota dysbiosis and reversed microbial metabolite changes.Finally,by integrating behavioural and neurological data with metabolomic profiles,we revealed that the underlying mechanism may involve the modulation of microbiota-derived glutamine metabolism via gut-brain interactions.Collectively,combined B.breve intervention with EE treatment can alleviate AD-related cognitive impairment and improve brain function by regulating glutamine metabolism of the gut microbiome.Our findings provide a promising multidomain intervention strategy,with a combination of dietary microbiome-based and lifestyle-targeted interventions,to promote brain function and delay the progression of AD.

Synergistic Effects of Glutamine Deprivation and Metformin in Acute Myeloid Leukemia

Objective The metabolic reprogramming of acute myeloid leukemia(AML)cells is a compensatory adaptation to meet energy requirements for rapid proliferation.This study aimed to examine the synergistic effects of glutamine deprivation and metformin exposure on AML cells.Methods SKM-1 cells(an AML cell line)were subjected to glutamine deprivation and/or treatment with metformin or bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide(BPTES,a glutaminase inhibitor)or cytarabine.Cell viability was detected by Cell Counting Kit-8(CCK-8)assay,and cell apoptosis and reactive oxygen species(ROS)by flow cytometry.Western blotting was conducted to examine the levels of apoptotic proteins,including cleaved caspase-3 and poly(ADP-ribose)polymerase(PARP).Moreover,the human long noncoding RNA(lncRNA)microarray was used to analyze gene expression after glutamine deprivation,and results were confirmed with quantitative RT-PCR(qRT-PCR).The expression of metallothionein 2A(MT2A)was suppressed using siRNA.Cell growth and apoptosis were further detected by CCK-8 assay and flow cytometry,respectively,in cells with MT2A knockdown.Results Glutamine deprivation or treatment with BPTES inhibited cell growth and induced apoptosis in SKM-1 cells.The lncRNA microarray result showed that the expression of MT family genes was significantly upregulated after glutamine deprivation.MT2A knockdown increased apoptosis,while proliferation was not affected in SKM-1 cells.In addition,metformin inhibited cell growth and induced apoptosis in SKM-1 cells.Both glutamine deprivation and metformin enhanced the sensitivity of SKM-1 cells to cytarabine.Furthermore,the combination of glutamine deprivation with metformin exhibited synergistic antileukemia effects on SKM-1 cells.Conclusion Targeting glutamine metabolism in combination with metformin is a promising new therapeutic strategy for AML.

Glutamine transporters as effective targets in digestive system malignant tumor treatment

Glutamine is one of the most abundant non-essential amino acids in human plasma and plays a crucial role in many biological processes of the human body.Tumor cells take up a large amount of glutamine to meet their rapid proliferation requirements,which is supported by the upregulation of glutamine transporters.Targeted inhibition of glutamine transporters effectively inhibits cell growth and proliferation in tumors.Among all cancers,digestive system malignant tumors(DSMTs)have the highest incidence and mortality rates,and the current therapeutic strategies for DSMTs are mainly surgical resection and chemotherapy.Due to the relatively low survival rate and severe side effects associated with DSMTs treatment,new treatment strategies are urgently required.This article summarizes the glutamine transporters involved in DSMTs and describes their role in DSMTs.Additionally,glutamine transportertarget drugs are discussed,providing theoretical guidance for the further development of drugs DSMTs treatment.

Dynamics of glutamine synthetase expression in hepatic ischemiareperfusion injury: Implications for therapeutic interventions

BACKGROUND Hepatic ischemia-reperfusion injury(IRI)poses a great challenge in liver surgery and transplantation because of oxidative stress and inflammatory responses.The changes in glutamine synthetase(GS)expression during hepatic IRI remain unclear.AIM To investigate the dynamic expression of GS during hepatic IRI.METHODS Following hepatic ischemia for 1 h and reperfusion,liver tissue samples were collected at 0.5,6,and 24 hours postreperfusion for fixation,embedding,section-ing.Hematoxylin and eosin staining and GS staining were performed.RESULTS GS expression rapidly decreases in hepatocytes around the central vein after IRI,reaching its lowest point at 6 hours postreperfusion,and then gradually recovers.CONCLUSION GS is highly sensitive to IRI,highlighting its potential role as an indicator of liver injury states and a target for therapeutic intervention.

Glutamine and Its Actions: A Bird’s Eye View

Glutamine (Gln) is the most abundant amino acid in the body, playing a versatile role in both maintaining homeostasis and contributing to various pathologies. This review explores the physiological functions of Gln, detailing its enzymatic synthesis and degradation, as well as its role across different organs, tissues and systems in both normal and pathological conditions. This review is a search of relevant topics related with Gln and its actions;its key areas discussed include the immune system, heat shock proteins, skeletal muscle, central nervous system, the intestinal mucosal barrier, liver, kidney, gluconeogenesis, types 1 and 2 diabetes, burns, cancer, and hepatic encephalopathy. While Gln demonstrates numerous beneficial effects, it can also contribute to adverse outcomes in specific diseases, such as cancer and hepatic encephalopathy. Despite these complexities, it is crucial to keep searching for glutamine’s role in health and disease. Understanding how Gln supplementation may support patients taking multidrug therapy to reduce the need for certain medications, and enhancing treatment adherence and disease management is particularly important.

Effects of Supplemental Glutamine and Lysine on Growth Performance of Broiler Chickens

The optimum levels of Lysine and Glutamine needed for growth performance and maintenance of the chicken broilers were evaluated in a randomized 3 × 4 factorial arrangement of dietary treatments. The battery cages measured 99 × 66 × 25 cm that can be sufficient for 5 birds. Day old Chicken broilers totaling 180 were assigned to dietary treatments comprising of 3 concentrations of Lysine (0.85, 1.14, and 1.42) each in combination with 4 concentrations of Glutamine (0, 1, 2, and 3). Each dietary treatment was replicated 3 times and each replication had 5 birds. The birds were given feed and water ad libitum with a 23-hour light regimen for a period of 4 weeks. Then, the experimental birds were evaluated for body weight gain, feed consumption, and feed conversion in order to determine their optimum requirement for dietary Lysine and Glutamine. Based on the findings of this study, the highest performance was observed in birds fed the diet supplemented with 1.42 lysine and 1% glutamine, but the highest improvement in feed conversion was observed in diet contain 1.14 and 1.42 with 1% and 3% glutamine, respectively. Birds fed 1.42 lysine and 1% glutamine had the highest total body weight gain and feed consumption. The lysine requirements in the diet for Chicken are between 1.14 and 1.42 with glutamine level of 1%.

Comparative Study of Immunological Properties on Glutamine Synthetase Isozymes in Rice Plants

In rice (Oryza sativa L.) roots two glutamine synthetase (GS) isozymes, GSra and GSrb, were identified recently in the author's experiments, but the homology of both GSra and GSrb as well as their localization in the rice roots are unclear. In the present study, the purified GSra and GSrb from rice roots were used to immunize rabbits to obtain the respective antibodies. The immunodiffusion and immunoblotting experiments showed that the antibody against GSra or GSrb was specific for GS and its isozymes. The immunoprecipitation test indicated that the antibody of GSra or GSrb not only recognized its respective antigen, but also well recognized each other's antigen. GSra or GSrb antibody recognized also better cytosolic GS1 of rice leaves, but the recognization for chloroplast GS2 from rice or spinach (Spinacia oleracea Mill.) leaves was weaker. Our results indicate that GSra and GSrb from rice roots are quite similar in antigenicity and are extremely similar proteins and that both GSra and GSrb may also be a form of cytosolic GS just as the cytosolic GS1 of rice leaves.

Glutamine or Glutamine Dipeptide Supplementation Improves Gluconeogenesis and Liver Glycogenosis in Type 1 Diabetic Rats

The effects of the supplementation with L-glutamine(GLN)or L-alanyl-L-glutamine(GDP)on the progression of the systemic and hepatic metabolic status of rats having untreated type 1 diabetes mellitus(T1DM)were investigated.Male Wistar diabetic rats(streptozotocin,60 mg/kg)were allotted to four groups supplemented by gavage for thirty days as follows:control and diabetic receiving saline;diabetic receiving GLN(248 mg/kg);and diabetic receiving GDP(400 mg/kg).Body weight,plasmatic parameters and kidney function were analyzed.Isolated hepatocytes were used to assess gluconeogenic capacity.Liver and kidney were used for morphological analyses.T1DM decreased the number and increased the area of the hepatocytes,possibly because of the observed enlargement of glycogen stores.Kidney weight,glomerular area and proteinuria increased,and glomerular filtration rate decreased,in non-supplemented T1DM rats.Glomerular area and proteinuria were reversed by both supplementations.The T1DM hepatocytes released less glucose,which could have been diverted to glycogen synthesis and secondary glycogenosis observed in T1DM;this was partially reversed by the supplementations.The results point to a possible beneficial effect of glutamine on the metabolic and hepatic impairments of T1DM.

Review:Do Horses Receive Optimum Amounts of Glutamine in Their Diets?

In some species of growing mammals glutamine is an essential amino acid that,if inadequate in the diet,is needed for normal growth and development.It is thus sometimes considered to be a conditionally essential amino acid in some species.A review of studies that have measured L-glutamine concentrations([glutamine])in horses demonstrates that plasma[glutamine]has routinely been reported to be much lower(~330μmol/L)than in other mammals(>600μmol/L).Plasma[glutamine]represents the balance between intestinal transport into the blood after hepatic first pass,tissue synthesis and cellular extraction.The hypothesis is proposed that sustained low plasma[glutamine]represents a chronic state of sub-optimal glutamine intake and glutamine synthesis that does not meet the requirements for optimum health.While this may be without serious consequence in feral and sedentary horses,there is evidence that provision of supplemental dietary glutamine ameliorates a number of health consequences,particularly in horses with elevated metabolic demands.The present review provides evidence that glutamine is very important(and perhaps essential)for intestinal epithelial cells in mammals including horses,that horses with low plasma[glutamine]represents a sub-optimal state of well-being,and that horses supplemented with glutamine exhibit physiological and health benefits.

Protective effect of glutamine on intestinal injury and bacterial community in rats exposed to hypobaric hypoxia environment

AIM: To investigate the protective effect of glutamine (Gln) on intestinal injury and the bacterial community in rats exposed to hypobaric hypoxia environment.

Glutamine is highly effective in preventing in vivo cobalt-induced oxidative stress in rat liver

AIM: To evaluate the in vivo effect of glutamine on cobaltgenerated oxidative stress and (HO-1) induction in rat liver.METHODS: Fasted female Wistar rats received a single injection of cobalt chloride (375 μmol/kg body weight) and then were killed at different times. Lipid peroxidation and soluble and enzymatic antioxidant defense system (reduced glutathione (GSH), catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD)) were measured in liver homogenates. Ferritin and ferritin iron contents as well as heme oxygenase-1 (HO-1) activity and expression were also determined. The antioxidant properties of glutamine (Gin) were also evaluated. RESULTS: Cobalt chloride increased lipid peroxidation (50% over control values) 1 h after treatment. GSH reached a minimum at 3 h (40%) increasing thereafter. Twelve hours after CoCl2 injection, the antioxidant enzymes CAT, GSH-Px and SOD also diminished by about 30%. Heme oxygenase-1 induction was observed 6 h after treatment reaching a maximum value of 14-fold over the controls, 12 h after cobalt treatment. A 1.7-fold increase in ferritin and ferritin-bound iron 24 h after treatment were also obtained. Administration of glutamine (300 mg/kg body weight) by gavage 24 h before CoCl2 treatment entirely prevented the increase in thiobarbituric acid reactive substances (TBARS) content, the decrease in GSH levels, and partially reverted heme oxygenase-1 induction. CONCLUSION: These results suggested that a natural product such as glutamine prevents glutathione depletion and consequently heme oxygenase induction.

Influences of Mo on Nitrate Reductase, Glutamine Synthetase and Nitrogen Accumulation and Utilization in Mo-Efficient and Mo-Inefficient Winter Wheat Cultivars

The objective is to study whether the accumulation and utilization of plant N are controlled by Mo status in winter wheat cultivars. Mo-efficient cultivar 97003 （eft） and Mo-inefficient cultivar 97014 （ineff） were grown in severely Mo-deficient acidic soil （Tamm-reagent-extractable Mo 0.112 mg kg^-1） with （＋Mo） and without （-Mo） the application of 0.13 mg kg^-1 Mo. The accumulation and use efficiency of plant total N were significantly higher in ＋Mo than that in -Mo and in eft than that in ineff under Mo deficiency. N use efficiency was remarkably higher in maturity but it was forwarded to jointing stage after Mo supply, thus indicating that Mo supply promoted the N use efficiency besides N uptake and eff was efficient in N uptake and utilization. The overall activity of nitrate reductase （NR, EC 1.6.6.1） was significantly higher in ＋Mo than in -Mo and ratio of ＋Mo/-Mo was even to 14.8 at filleting stage for ineff. Activity of glutamine synthetase （GS, EC 6.3.1.2） was significantly lower in ＋Mo than in -Mo. Concentration of nitrate and glutamate were also significantly lower in ＋Mo than in -Mo, thus provided evidences for enhancing N use efficiency by Mo supply. Activities of NR and GS were significantly higher and concentrations of nitrate and glutamate were significantly lower in eff than ineff under Mo deficiency, thus indicated eff was more efficient in N reduction and utilization. It is therefore concluded that Mo could promote N accumulation and utilization in winter wheat which was directly related to NR and feedback regulated by GS. Higher Mo status also results in higher accumulation and utilization of plant N in eft.

Glutamine:aprecursor of glutathione and its effect on liver

AIM To investigate the relationship between alanyl-glutamine (ALA-GLN) and glutathione (GSH) biosynthesis in hepatic protection.METHODS Twenty male Wistar rats were randomly divided into two groups: one receiving standard parenteral nutrition (STD) and the other supplemented with or without ALA-GLN for 7 days. The blood and liver tissue samples were examined after 5-fluorouracil (5-FU) was injected peritoneally.RESULTS The concentration measurements were significantly higher in ALA-GLN group than in STD group in serum GLN (687 μmol/ L±50 μmol/ L vs 505 μmol/ L±39 μmol/ L, P＜0.05), serum GSH (14 μmol/ L±5 μmol/ L vs 7 μmol/ L±3 μmol/ L, P＜0.01) and in liver GSH content (6.9 μmol/ g±2.5 μmol/ g vs 4.4 μmol/ g±1.6 μmol/ g liver tissue, P＜0.05). Rats in ALA-GLN group had lesser elevations in hepatic enzymes after 5-FU administration.CONCLUSION The supplemented nutrition ALA-GLN can protect the liver function through increasing the glutathione biosynthesis and preserving the glutathione stores in hepatic tissue.

Effects of creep feeding and supplemental glutamine or glutamine plus glutamate (Aminogut) on pre- and post-weaning growth performance and intestinal health of piglets

Background： Creep feeding is used to stimulate piglet post-weaning feed consumption.L-Glutamine（GLN） is an important source of fuel for intestinal epithelial cells.The objective of this study was to determine the impact of creep feeding and adding GLN or AminoGut（AG;containing glutamine ＋ glutamate） to pre-and post-weaning diets on pig performance and intestinal health.Litters（N = 120） were allotted to four treatments during 14–21 d of lactation： 1） No creep feed（NC,n = 45）;2） creep fed control diet（CFCD,n = 45）;3） creep fed 1% GLN（CFGLN,n = 15）;4） creep fed.88% AG（CFAG,n = 15）.After weaning,the NC and CFCD groups were sub-divided into three groups（n = 15 each）,receiving either a control nursery diet（NC-CD,CFCD-CD） or a diet supplemented with either GLN（NC-GLN,CFCD-GLN） or with AG（NC-AG,CFCD-AG）.Litters that were creep fed with diets containing GLN or AG also were supplemented with those amino acids in the nursery diets（CFGLN-GLN,CFAG-AG）.Glutamine was added at 1% in all three post-weaning diet phases and AG was added at.88% in phase 1 and 2 and at.66% in phase 3.Results： Feed conversion（feed/gain） showed means among treatment means close to significance（P = 0.056） and Tukey＇s test for pairwise mean comparisons showed that Pigs in the CFGLN-GLN group had the best feed conversion（feed/gain） in the first three-week period post-weaning,exceeding（P = 0.044） controls（CFCD-CD） by 34%.The NC-AG group had（P = 0.02） the greatest feed intake in the last three week of the study,exceeding controls（CFCD-CD） by 12%.CFGLN-GLN,CFCD-GLN and sow reared（SR） pigs had the greatest（P = 0.049） villi height exceeding the CFCD-AG group by 18%,20% and 19% respectively.The CFAG-AG group had the deepest（P = 0.001） crypts among all treatments.CFGLN-GLN,CFCD-GLN and SR groups had the greatest（P = 0.001） number of cells proliferating（PCNA） exceeding those in the NC-CD group by 43%,54% and 63% respectively.Sow reared pigs showed the greatest（P = 0.001） intestinal absorption capacity for xylose and mannitol.Conclusion： Supplementation of creep feed and nursery diets with GLN and/or AminoGut in the first three week improved feed conversion possibly due to improved intestinal health.

Effect of Nitrate on Activities and Transcript Levels of Nitrate Reductase and Glutamine Synthetase in Rice

Real-time polymerase chain reaction analysis was used to compare the effect of NO3^- on the activities of nitrate reductase （NR） and glutamine synthetase （GS）, and the transcript levels of two NR genes, OsNial and OsNia2, two cytosolic GS1 genes, OsGln1;1 and OsGln1;2, and one plastid GS2 gene OsGln2, in two rice （Oryza sativa L.） cultivars Nanguang （NG） and Yunjing （Y J）. Both cultivars achieved greater biomass and higher total N concentration when grown in a mixed N supply than in sole NH4^＋ nutrition. Supply of NO3^- increased NR activity in both leaves and roots. Expression of both NR genes was also substantially enhanced and transcript levels of OsNia2 were significantly higher than those of OsNial. NO3 also caused an increase in GS activity, but had a complex effect on the expression of the three GS genes. In roots, the OsGln1;1 transcript increased, but OsGln1;2 decreased. In leaves, NO3^- had no effect on the GS1 expression, but the transcript for OsGln2 increased both in the leaves and roots of rice with a mixed supply of N. These results suggested that the increase in GS activity might be a result of the complicated regulation of the various GS genes. In addition, the NO3-induced increase of biomass, NR activity, GS activity, and the transcript levels of NR and GS genes were proportionally higher in NG than in Y J, indicating a stronger response of NG to NO3^- nutrition than YJ.

Glutamine dipeptide for parenteral nutrition in abdominal surgery:A meta-analysis of randomized controlled trials

AIM: To assess the clinical and economical validity of glutamine dipeptide supplemented to parenteral nutrition (PN) in patients undergoing abdominal surgery. METHODS: A meta-analysis of all the relevant randomized controlled trials (RCTs) was performed. The trials compared the standard PN and PN supplemented with glutamine dipeptide in abdominal surgery. RCTs were identified from the following electronic databases: the Cochrane Library, MEDLINE, EMBASE and ISI web of knowledge (SCI). The search was undertaken in April 2006. Literature references were checked by computer or hand at the same time. Clinical trials were extracted and evaluated by two reviewers independently. Statistical analysis was performed by RevMan4.2 software from Cochrane Collaboration. A P value of < 0.05 was considered statistically significant. RESULTS: Nine RCTs involving 373 patients were included. The combined results showed that glutamine dipeptide has a positive effect in improving postoperative cumulative nitrogen balance (weighted mean difference (WMD = 8.35, 95% CI [2.98, 13.71], P = 0.002), decreasing postoperative infectious morbidity (OR = 0.24, 95% CI [0.06, 0.93], P = 0.04), shortening the length of hospital stay (WMD= -3.55, 95% CI [-5.26, -1.84], P < 0.00001). No serious adverse effects were found. CONCLUSION: Postoperative PN supplemented with glutamine dipeptide is effective and safe to decrease the infectious rate, reduce the length of hospital stay and improve nitrogen balance in patients undergoing abdominal surgery. Further high quality trials in children and severe patients are required, and mortality and hospital cost should be considered in future RCTs with sufficient size and rigorous design.

Enteral nutrition combined with glutamine promotes recovery after ileal pouch-anal anastomosis in rats

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.

Antioxidant properties of glutamine and its role in VEGF-Akt pathways in portal hypertension gastropathy

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.

Glutamate reduces experimental intestinal hyperpermeability and facilitates glutamine support of gut integrity

AIM:To assess whether glutamate plays a similar role to glutamine in preserving gut wall integrity.METHODS:The effects of glutamine and glutamate on induced hyperpermeability in intestinal cell lines were studied.Paracellular hyperpermeability was induced in Caco2.BBE and HT-29CL.19A cell lines by adding phorbol-12,13-dibutyrate(PDB) apically,after which the effects of glutamine and glutamate on horseradish peroxidase(HRP) diffusion were studied.An inhibitor of glutamate transport(L-trans-pyrrolidine-2,4-dicarboxylic acid:trans-PDC) and an irreversible blocker(acivicin) of the extracellular glutamine to glutamate converting enzyme,γ-glutamyltransferase,were used.RESULTS:Apical to basolateral HRP flux increased significantly compared to controls not exposed to PDB (n=30,P<0.001).Glutamine application reduced hyperpermeability by 19%and 39%in the respective cell lines.Glutamate application reduced hyperpermeability by 30%and 20%,respectively.Incubation of HT29CL.19A cells with acivicin and subsequent PDB and glutamine addition increased permeability levels.Incubation of Caco2.BBE cells with trans-PDC followed by PDB and glutamate addition also resulted in high permeability levels.CONCLUSION:Apical glutamate-similar to glutaminecan decrease induced paracellular hyperpermeability.Extracellular conversion of glutamine to glutamate and subsequent uptake of glutamate could be a pivotal step in the mechanism underlying the protective effect of glutamine.