Effect Of L-glutamine Research Articles

Effect of L-Glutamine on Chylomicron Formation and Fat-Induced Activation of Intestinal Mucosal Mast Cells in Sprague-Dawley Rats.

Glutamine (Gln) is required for intestinal mucosal homeostasis, and it can promote triglyceride absorption. The intestinal mucosal mast cells (MMCs) are activated during fat absorption. This study investigated the potential role of Gln on fat absorption-induced activation of MMCs in rats. Lymph fistula rats (n = 24) were studied after an overnight recovery with the infusion of saline only, saline plus 85 mM L-glutamine (L-Gln) or 85 mM D-glutamine (D-Gln), respectively. On the test day, rats (n = 8/group) were given an intraduodenal bolus of 20% Intralipid contained either saline only (vehicle group), 85 mM L-Gln (L-Gln group), or 85 mM D-Gln (D-Gln group). Lymph was collected hourly for up to 6 h for analyses. The results showed that intestinal lymph from rats given L-Gln had increased levels of apolipoprotein B (ApoB) and A-I (ApoA-I), concomitant with an increased spectrum of smaller chylomicron particles. Unexpectedly, L-Gln also increased levels of rat mucosal mast cell protease II (RMCPII), as well as histamine and prostaglandin D2 (PGD2) in response to dietary lipid. However, these effects were not observed in rats treated with 85 mM of the stereoisomer D-Gln. Our results showed that L-glutamine could specifically activate MMCs to degranulate and release MMC mediators to the lymph during fat absorption. This observation is potentially important clinically since L-glutamine is often used to promote gut health and repair leaky gut.

The effect of L-glutamine and trehalose on dog sperm cryopreservation

This study aimed to test different doses of L-glutamine and trehalose in the canine semen diluent while determining their protective effects on spermatological and biochemical indices of the thawed samples. Semen samples were collected from three fertile dogs using the digital manipulation method. The mixed ejaculates were divided into five portions at 37 °C and diluted with additives. Five study groups were formed with L-glutamine (10 and 20 mM), trehalose (25 and 50 mM), and no additives (control). After the dilution, the semen samples were cooled for 1.5 h at 5 °C and frozen (-110 to -120 °C) in liquid nitrogen vapor. Then, they were stored at -196 °C. For spermatological evaluations, samples were thawed at 38 °C for 30 s. L-glutamine (20 mM) was found to be significantly different (P < 0.05) and led to higher percentages of motility, membrane integrity, and acrosome integrity compared to the control group. Considering the total oxidant status (TOS) assay, the lower values were determined in all the antioxidant groups compared to the control group (P < 0.05). Supplementing the semen extender with L-glutamine showed a higher total antioxidant status (TAS) concentration compared to the control group (P < 0.05). As a result of this study, a higher protective effect was found in all the spermatological evaluations after thawing the frozen semen samples, especially in the group containing L-glutamine (20 mM).

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.

The effects of L-glutamine on castor oil induced diarrhea in albino Wistar rats

The effects of L-glutamine on castor oil induced diarrhea in albino Wistar rats

The effects of L-glutamine on castor oil induced diarrhea in albino Wistar rats

Diarrhea is the condition of having three or more loose or liquid stools per day or as having more stool than normal. L-glutamine is an amino acid derived from glutamic acid. Diarrhea is a leading cause of childhood morbidity and mortality in the developing Countries. World Health Organization predicts that; there will be about 5 million deaths in children younger than five years by 2025, of which 97% will be in the developing countries. This study assessed the effects of l-glutamine on castor oil induced diarrhea in albino Wistar rats. The Study was carried out on castor oil induced diarrhea, gastrointestinal motility and on isolated rabbit jejunum. The value of (P

Inhibition of pyruvate dehydrogenase kinase-4 by l-glutamine protects pregnant rats against fructose-induced obesity and hepatic lipid accumulation

ObjectiveAccumulation of lipids in non-adipose tissues particularly the liver is a feature of tissue insulin resistance. Hepatic glycogen depletion reflects counter glucoregulation in an insulin-resistant state and/or obesity. The effect of l-glutamine on fructose-induced increased hepatic lipid accumulation and depleted glycogen content, particularly in pregnancy, is not known. We therefore aimed at investigating the effect of glutamine on fructose-induced weight gain, hepatic lipids and glycogen contents in pregnant rats and also tested the hypothesis that hepatoprotective role of l-glutamine is through suppression of PDK-4. MethodsEleven-week-old pregnant Wistar rats were allotted into the Control, Glutamine, Fructose and Fructose plus Glutamine groups (6 rats/group). The groups received distilled water (vehicle, p.o.), 1 g/kg bwl-glutamine (p.o.), 10% Fructose (w/v) and 10% Fructose (w/v) plus 1 g/kg bwl-glutamine (p.o.) respectively, daily for 19 days. Biochemical analysis and histology of the liver were performed. ResultsData showed that fructose intake caused insulin resistance, hyperglycemia, hyperlipidemia, increased body weight gain, visceral fat mass, hepatic mass, lactate production, uric acid production, lipid peroxidation and decreased pancreatic β-cell function and hepatic glycogen synthesis. These alterations were accompanied by elevated pyruvate dehydrogenase kinase-4 (PDK-4). However, the fructose-induced dysmetabolism were improved by l-glutamine. ConclusionOur results demonstrate that obesity and hepatic lipid accumulation induced by fructose in pregnant rats is accompanied by increased PDK-4. The findings also suggest that l-glutamine would protect against obesity and hepatic lipid accumulation by suppression of PDK-4.

Analysis of Nitrogen Utilization Capability during the Proliferation and Maturation Phases of Norway Spruce (Picea abies (L.) H.Karst.) Somatic Embryogenesis

Somatic embryogenesis (SE) is a laboratory-based method that allows for cost-effective production of large numbers of clonal copies of plants, of particular interest for conifers where other clonal propagation methods are mostly unavailable. In this study, the effect of l-glutamine as an organic nitrogen source was evaluated for three contrasted media (containing NH4 + NO3 without glutamine, or glutamine + NO3, or glutamine without inorganic nitrogen) during proliferation and maturation of Norway spruce somatic embryos through analyses of activities of the key enzymes of nitrogen metabolism: nitrate reductase (NR), glutamine synthetase (GS) and arginase. A major change in nitrogen metabolism was indicated by the increased activity of GS from zero in the proliferation stage through maturation to high activity in somatic embryo-derived plantlets; furthermore, NR activity increased from zero at the proliferation stage to high activity in maturing embryos and somatic-embryo derived plantlets. In contrast, arginase activity was high at all stages. In accordance with the GS and NR data, proliferation was fastest on the glutamine media, the largest number of mature embryos developed on the glutamine medium without inorganic nitrogen, and the ammonium content of proliferating cultures was much higher than that of mature somatic embryos. The best developed embryos, judged by germination, were from the glutamine + NO3 medium. These insights into nitrogen utilization will help to improve culture medium composition.

Effects of L-glutamine on boar sperm quality during liquid storage at 17°C

The quality of boar spermatozoa is affected by oxidative stress during preservation in vitro. It has been demonstrated that L-Glutamine (Gln) can effectively protect cells from oxidative stress-induced injury. There are, however, no reports to date evaluating the effects of Gln on boar semen liquid preservation at 17 °C. The aims of the present study were to elucidate whether the addition of Gln to the extender BTS could improve the quality of boar spermatozoa when stored at 17 °C and to determine the mechanism underlying Gln protection of spermatozoa against preservation-induced damage. Boar semen samples were collected and diluted with Beltsville Thawing Solution (BTS) containing different concentrations (0, 10, 20, 40 or 80 mM) of Gln. The results indicated the addition of 20 mM Gln to the BTS improved (P < 0.05) the motility, acrosome integrity and membrane integrity of boar sperm during liquid preservation. Interestingly, treatment of spermatozoa with Gln addition to the extender resulted in ROS quenching, while enhancing γ-glutamyl cysteine synthetase (γ-GCS) activity, and glutathione (GSH) content of spermatozoa. These results suggest that BTS supplemented with Gln can provide greater protective capacity to boar sperm against oxidative stress by enhancing GSH synthesis during liquid preservation.

Effect of L-glutamine in late gestation sow diets on survivability and growth of piglets

Effect of L-glutamine in late gestation sow diets on survivability and growth of piglets

Effects of L-glutamine on growth performance, antioxidant ability, immunity and expression of genes related to intestinal health in weanling pigs

Although there were many reports about the L-glutamine (Gln) on growth performance and intestine health, little studies were conducted to determine the effects of Gln on nutrient digestibility and expression of genes related to intestinal health. Besides, the glutamic acid with lower price was assumed to substitute the glutamine partly, which can partly be synthesized by the glutamic acid. Therefore, this study was conducted to determine the effects of Gln on growth performance, apparent total tract digestibility (ATTD), blood profiles, related enzyme activity, small intestinal mucosal morphology and expression of genes related to intestinal health in weanling pigs. A total of 250 [(Landrace× Yorkshire)× Duroc] pigs (9.22±0.11kg) were blocked on the basis of sex and body weight, and then randomly assigned to 1 of the following 5 treatments: 1) CON (basal diet); 2) 1/9 Gln/Glu (CON +0.1% Gln +0.9% Glu); 3) 2/8 Gln/Glu (CON +0.2% Gln +0.8% Glu); 4) 1% Gln (CON +1% Gln); 5) 1% Glu (CON +1% Glu). There were 5 replications (pens) per treatment and 10 pigs per pen in this 28-d experiment. Pigs fed the 1% Gln diet had a higher ADG and G: F (P<0.05) than those fed CON diet during d 0–14 and the overall period. The ATTD of dry matter (DM) and nitrogen (N) was the greatest (P<0.05) in response to the 1% Gln diet on d 28. Compared with CON, feeding the 1% Gln diet increased (P<0.05) the content of superoxide dismutase (SOD), while it decreased (P<0.05) the malondialdehyde (MDA) content on d 28 in the serum. The levels of immunoglobulin G (IgG) and immunoglobulin M (IgM) in the serum was increased in the 1% Gln group (P<0.05), whereas the percentage of the cluster of differentiation 8 receptors (CD8+) was reduced (P<0.05) in the 1% Gln group compared with CON. The activity of lactase was improved (P<0.05) in pigs fed the 1% Gln diet compared with those fed CON diet. However, the activity of glutamine synthetase (GS) was reduced (P<0.05) in pigs fed Gln1, Gln2, the 1% Gln and 1% Glu diets compared with those fed CON diet. Feeding of the 1% Gln diet declined (P<0.05) the relative expression levels of peroxisome proliferator-activated receptor γ (PPARγ) and mammalian target of rapamycin (mTOR), while improving (P<0.05) the relative expression level of pyruvate kinase (PK) in the duodenum, jejunum and ileum, respectively, compared with CON. Taken together, the 1% Gln supplementation to weanling pig diets could modify intestinal health and improve ATTD of nutrients so as to benefit the growth performance. Nevertheless, the Gln/Glu use could not achieve the effects of 1% Gln group in this study.

The Influence of Oral L-Glutamine Supplementation on Muscle Strength Recovery and Soreness Following Unilateral Knee Extension Eccentric Exercise

The study aimed to examine the effects that L-glutamine supplementation has on quadriceps muscle strength and soreness ratings following eccentric exercise. It was hypothesized that glutamine ingestion would quicken the recovery rate of peak force production and decrease muscle soreness ratings over a 72-hr recovery period. Sixteen healthy participants (8♀/8♂; 22 ± 4 years) volunteered in a double-blind, randomized, placebo-controlled crossover study. Supplement conditions consisted of isoenergetic placebo (maltodextrin, 0.6 g·kg-1·day-1) and L-glutamine (0.3 g·kg-1·day-1 + 0.3 g·kg-1·day-1 maltodextrin) ingestion once per day over 72 hr. Knee extensor peak torque at 0°, 30°, and 180° per second and muscle soreness were measured before, immediately following, 24, 48, and 72 hr posteccentric exercise. Eccentric exercise consisted of 8 sets (10 repetitions/set) of unilateral knee extension at 125% maximum concentric force with 2-min rest intervals. L-glutamine resulted in greater relative peak torque at 180°/sec both immediately after (71 ± 8% vs. 66 ± 9%), and 72 hr (91 ± 8% vs. 86 ± 7%) postexercise (all, p < .01). In men, L-glutamine produced greater (p < .01) peak torques at 30°/ sec postexercise. Men also produced greater normalized peak torques at 30°/sec (Nm/kg) in the L-glutamine condition than women (all, p < .05). In the entire sample, L-glutamine resulted in lower soreness ratings at 24 (2.8 ± 1.2 vs. 3.4 ± 1.2), 48 (2.6 ± 1.4 vs. 3.9 ± 1.2), and 72 (1.7 ± 1.2 vs. 2.9 ± 1.3) hr postexercise (p < .01). The L-glutamine supplementation resulted in faster recovery of peak torque and diminished muscle soreness following eccentric exercise. The effect of L-glutamine on muscle force recovery may be greater in men than women.

Protective effects of L-glutamine on hepatic injury of brain-dead rats

Objective To explore the effct of L-glutamine (Gln) on hepatic injury of brain-dead rats.Methods Thirty-two SD rats were randomly assigned into 4 groups:control group (C),brain death group (B) and Gln protection groups (G1,G2).Brain death models were established in groups B,group G1 and group G2.The sera of rats at 6 h were collected and the levels of alanine aminotransferase ( ALT),aspartate aminotransferase (AST),tumor necrosis factor-α (TNF-α) and endothelin-1 (ET-1) were determined.At end of assisted respiration,samples of liver were collected and the ulrastructures were observed.Results At 6th h after brain death,the levels of ALT [ ( 184.45 ± 19.96) U/L],AST [ (387.68 ± 15.57)U/L],TNF-α [ (62.35 ±2.75) ng/L] and ET-1 [ (221.43 ± 15.62) ng/L] in group B were significantly higher than those in group C:ALT [(52.25 ±9.36) U/L],AST [(176.45 ±8.40) U/L],TNF-α [ (27.63 ±4.42) ng/L] and ET-1 [ (70.32 ± 5.83 ) ng/L] (P ＜ 0.05).The levels of ALT [ ( 100.02 ±20.36) U/L],AST [ (260.32 ± 16.42) U/L],TNF-α [ (42.31 ± 1.69) ng/L] and ET-1 [ ( 142.56 ±11.25) ng/L] in group G2 were significantly different from those in group G1:ALT [ (148.77 ± 16.75)U/L],AST [(299.35±15.46) U/L],TNF-α [(52.09±3.26) ng/L],ET-1 [(162.45 ±13.87)ng/L],and group B:ALT [(184.45 ± 19.96) U/L],AST [(387.68 ± 15.57) U/L],TNF-α [(62.35 ±2.75) ng/L] and ET-1 [(221.43 ±15.62) ng/L] (P＜0.05).Conclusion Brain death can cause serious damage to the liver of rats.Gln can relieve the hepatic injury of brain death donors. Key words: Brain death; Glutamine; Liver; Endothelin

L-Arginine but not l-glutamine likely increases exogenous carbohydrate oxidation during endurance exercise

The addition of L-arginine or L-glutamine to glucose-electrolyte solutions can increase intestinal water, glucose, and sodium absorption in rats and humans. We evaluated the utility of L-arginine and L-glutamine in energy-rehydration beverages through assessment of exogenous glucose oxidation and perceptions of exertion and gastrointestinal distress during endurance exercise. Eight cyclists rode 150 min at 50% of peak power on four occasions while ingesting solutions at a rate of 150 mL 15 min(-1) that contained (13)C-enriched glucose (266 mmol L(-1)) and sodium citrate ([Na(+)] 60 mmol L(-1)), and either: 4.25 mmol L(-1) L-arginine or 45 mmol L(-1) L-glutamine, and as controls glucose only or no glucose. Relative to glucose only, L-arginine invoked a likely 12% increase in exogenous glucose oxidation (90% confidence limits: ± 8%); however, the effect of L-glutamine was possibly trivial (4.5 ± 7.3%). L-Arginine also led to very likely small reductions in endogenous fat oxidation rate relative to glucose (12 ± 4%) and L-glutamine (14 ± 4%), and relative to no glucose, likely reductions in exercise oxygen consumption (2.6 ± 1.5%) and plasma lactate concentration (0.20 ± 0.16 mmol L(-1)). Effects on endogenous and total carbohydrate oxidation were inconsequential. Compared with glucose only, L-arginine and L-glutamine caused likely small-moderate effect size increases in perceptions of stomach fullness, abdominal cramp, exertion, and muscle tiredness during exercise. Addition of L-arginine to a glucose and electrolyte solution increases the oxidation of exogenous glucose and decreases the oxygen cost of exercise, although the mechanisms responsible and impact on endurance performance require further investigation. However, L-arginine also increases subjective feelings of gastrointestinal distress, which may attenuate its other benefits.

Modulation of murine blastocyst hatching in vitro by glutamine and tryptophan

Enrichment of culture media with amino acids improves embryo development. However, little is known about the specific action of each amino acid during embryogenesis. The present study was undertaken to examine the effect of L-glutamine (Gln) and tryptophan (Trp) on mouse embryo hatching, expansion and viability in vitro. Blastocysts were collected from 6- to 8-week-old female BALB/c mice (N = 30) and cultured in M2 medium containing either 0.125, 0.25 or 0.5 mM Trp, 1 mM Gln, or M2 alone. Gln significantly increased (100%; P < 0.05) blastocyst hatching at 24 h compared to M2 alone or Trp; moreover, Trp inhibited blastocyst hatching when compared to M2 alone (P < 0.05) at 72 h. In contrast, the percentage of embryos reaching the state of expanded blastocyst at 48 h was significantly higher in medium with 1 mM Gln (66.6%; P < 0.05) or with 0.125 mM Trp (61.1%; P < 0.05). Unexpectedly, Trp increased the percentage of degenerated blastocysts after 48 h (67.7%; P < 0.05), while Gln preserved blastocyst viability. These results suggest that Gln may enhance blastocyst hatching, expansion and viability in vitro.

P.6.007 Effect of L-glutamine and its dipeptides on the level of voluntary alcohol consumption in rats

We have performed a case-control analysis of dopamine D2-like receptor (DRD2, DRD3 and DRD4) gene polymorphisms in 118 Han Chinese cases with bipolar affective disorder and 196 control subjects, and replication analysis in 157 English cases and 143 control subjects. We found association between a functional DRD2 promoter variant (P=0.03 by allele) and the DRD2 taq1A polymorphism (P=0.001 by allele) in Chinese bipolar disorder patients. However, this finding was not replicated in the Caucasian subjects, indicating that the significant association we observed in the Chinese population is a false positive finding. An alternative explanation is that these polymorphisms are risk factors in Chinese but not Caucasian populations, a hypothesis which seems unlikely in view of the similarity of the clinical characteristics of bipolar disorder in the two populations. We also report a novel, rare one-repeat variant of the DRD4 exon 3 VNTR repeat in Chinese populations, which appears to be absent in Caucasians and is not associated with disease.

Studies on the effect of l-glutamine on morphology, structure, optical, mechanical and electrical properties of TGS crystal

Single crystals of l-glutamine doped triglycine sulfate (LGTGS) were grown from aqueous solution by low-temperature solution growth technique using slow cooling method. The LGTGS crystals exhibit prominent morphological changes in the (1 0 1) and (0 1 0) planes. Lattice parameter values were determined by single-crystal XRD analysis. The powder X-ray diffraction confirms the crystalline nature of LGTGS. The presence of dopants in the crystal lattice was qualitatively confirmed by FTIR analysis. The UV–vis–NIR spectrum was recorded to study the optical transparency of the grown crystals. Microhardness studies were carried out using Leitz Weitzler hardness tester at room temperature. The dielectric studies were carried out to identify the phase transition temperature and the dielectric behavior. The P– E hysteresis loops were recorded at 50 Hz to find the values of spontaneous polarization ( P s) and coercive field ( E c).

116 EFFECTS OF l-GLUTAMINE ON CRYOPRESERVATION OF IMMATURE BOVINE OOCYTES

The cryopreservation of bovine oocytes remains a challenge despite significant reported progress. Immature bovine oocytes have a complex structure and the conventional cryoprotectants (penetrating cryoprotectants, sugars, and macromolecules) appear to be not sufficient to preserve them efficiently during freezing. Studies on semen and fibroblast cryopreservation indicate that amino acids, particularly l-glutamine, protect enzymes during freezing and increase the post-thaw viability. Therefore, the amino acids may optimize oocyte cryopreservation when associated with conventional cryoprotectants. This work evaluated the effect of l-glutamine on cryopreservation of immature bovine oocytes after in vitro maturation. Oocytes with homogeneous cytoplasm and several cumulus cell layers from slaughterhouse ovaries were distributed randomly in three groups: non-vitrified control, vitrified control, and vitrified with l-glutamine. Oocytes from vitrified groups were exposed for 10 min to PBS + 10% FCS + 10% ethylene glycol (EG) + 0.25 m trehalose (T), and for 30 s to PBS + 10% FCS + 25% EG + 25% dimethylsulfoxide + 0.5 m T at room temperature, adding 80 mm l-glutamine for the third group. Oocytes were loaded into OPS and plunged in liquid nitrogen. For thawing, OPS were immersed in PBS + 10% FCS + 10% EG + 1 m T for three min. Oocytes werethen placed in PBS + 10% FCS + 0.5 m T and in PBS + 10% FCS, remaining three min in each solution. For in vitro maturation, oocytes were washed three times on holding medium (TCM-HEPES + FCS + pyruvate + gentamycin), washed three times in maturation medium (TCM-bicarbonate + FCS + pyruvate + gentamycin + hCG + FSH + estradiol), and cultured in microdrops (90 μL) of maturation medium covered with mineral oil at 38.5°C under 5% CO2 in air and high humidity for 24 h. Oocytes were denuded, fixed in paraformaldehyde and triton, stained with Hoechst 33342, and evaluated under epifluorescence microscopy. Oocytes at metaphase II were considered matured. The group vitrified with l-glutamine had a significantly higher maturation rate than the group vitrified without l-glutamine; however, both had significantly lower maturation rates than the non-vitrified control group. In conclusion, l-glutamine improved the viability of vitrified oocytes. Table 1. Oocyte maturation rates of non-vitrified control, vitrified control, and vitrified with glutamine groups This work was supported by FAPESP 03/08543-1.

Mitochondrial glutathione depletion by glutamine in growing tumor cells

The effect of l-glutamine (Gln) on mitochondrial glutathione (mtGSH) levels in tumor cells was studied in vivo in Ehrlich ascites tumor (EAT)–bearing mice. Tumor growth was similar in mice fed a Gln-enriched diet (GED; where 30% of the total dietary nitrogen was from Gln) or a nutritionally complete elemental diet (SD). As compared with non–tumor-bearing mice, tumor growth caused a decrease of blood Gln levels in mice fed an SD but not in those fed a GED. Tumor cells in mice fed a GED showed higher glutaminase and lower Gln synthetase activities than did cells isolated from mice fed an SD. Cytosolic glutamate concentration was 2-fold higher in tumor cells from mice fed a GED (∼4 mM) than in those fed an SD. This increase in glutamate content inhibited GSH uptake by tumor mitochondria and led to a selective depletion of mitochondrial GSH (mtGSH) content (not found in mitochondria of normal cells such as lymphocytes or hepatocytes) to ∼57% of the level found in tumor mitochondria of mice fed an SD. In tumor cells of mice fed a GED, 6-diazo-5-norleucine– or l-glutamate-γ-hydrazine–induced inhibition of glutaminase activity decreased cytosolic glutamate content and restored GSH uptake by mitochondria to the rate found in EAT cells of mice fed an SD. The partial loss of mtGSH elicited by Gln did not affect generation of reactive oxygen intermediates (ROIs) or mitochondrial functions (e.g., intracellular peroxide levels, O 2 − • generation, mitochondrial membrane potential, mitochondrial size, adenosine triphosphate and adenosine diphosphate contents, and oxygen consumption were found similar in tumor cells isolated from mice fed an SD or a GED); however, mitochondrial production ROIs upon TNF-α stimulation was increased. Our results demonstrate that glutamate derived from glutamine promotes an inhibition of GSH transport into mitochondria, which may render tumor cells more susceptible to oxidative stress-induced mediators.

Effects of L-glutamine on post-ischaemic cardiac function: protection and rescue.

We investigated the effects of L-glutamine (0-20 mM) on cardiac function. The isolated perfused working rat heart (left atrial and aortic pressures of 5 and 70 cm H2O, respectively) was subjected to 20 min of normothermic low-flow ischaemia followed by reperfusion for 35 min. In the absence of glutamine, ischaemia-reperfusion caused an immediate significant (P < 0.01) fall in cardiac output from 46 to 20 ml/min, with a further deterioration to 17 ml/min at 35 min reperfusion. Ischaemia also caused a significant (P < 0.05) fall in myocardial glutamate from 2.6 to 1.8 mumol/g wet weight; and ischaemia-reperfusion caused significant (each P < 0.05) diminutions of myocardial ATP from 3.5 to 1.0 mumol/g wet weight and phosphocreatine from 4.8 to 1.5 mumol/g wet weight and resulted in significant (P < 0.05) accumulation of myocardial lactate from 0.9 to 4.3 mumol/g wet weight. Glutamine, present throughout the perfusion protocol (i.e. prior to ischaemia), at or above 1.25 mM, prevented the post-ischaemic diminution of cardiac output and the deleterious changes in myocardial metabolites. Post-ischaemic treatment with glutamine at 2.5 mM completely prevented the post-ischaemic diminution of cardiac output and restored the myocardial metabolites to normal. Glutamine may be suitable as a cardioprotective and rescue agent. These effects may be mediated by maintenance of myocardial glutamate, ATP and phosphocreatine: and prevention of lactate accumulation.

Effect of L-glutamine and n-butyrate on the restitution of rat colonic mucosa after acid induced injury.

L-glutamine and n-butyrate are important nutrients for colonocytes affecting both their structure and function. The effect of these epithelial substrates on resealing of rat distal colon after acid induced injury was studied. Isolated colonic mucosa of 32 rats was mounted in Ussing chambers and exposed to Krebs-Ringer solution for four hours. Epithelial injury was induced by short-term exposure to luminal hydrochloric acid and resealing was studied with or without added glutamine or butyrate. Glutamine (luminal and serosal) reduced tissue conductance, mannitol and lactulose permeability, and permeation of enteropathogenic Escherichia coli. Glutamine (serosal) diminished conductance and mannitol permeability. Both interventions stimulated bromodeoxyuridine incorporation in nuclei of colonocytes. Luminal butyrate had no measurable effect on these parameters. These data suggest that L-glutamine stimulates repair mechanisms of rat colonic mucosa after acid injury. This effect on the gut barrier is associated with a stimulation of crypt cell proliferation. The addition of glutamine to parenteral solutions may be beneficial for patients under intensive care whose intestinal barrier is weakened in the course of sepsis and trauma.