Glutamine Group Research Articles

Effect of glutamine on oral mucositis in patients undergoing chemotherapy-radiotherapy: A Randomized Clinical Trial

Background: In most malignant diseases, chemotherapy drugs are used as a main complementary method of treatment and have different side effects, which should not be overlooked if we are to provide complete treatment for the patient. These complications include inflammation and oral wounds, referred to as mucositis. This study aimed to investigate the effect of glutamine on oral mucositis in patients undergoing chemotherapy-radiotherapy. Methods: The present conducted on 40 patients with head and neck tumors undergoing chemotherapy or radiotherapy. Each patient was placed in a group that received either the drug (glutamine) or placebo (maltodextrin) based on a random even or odd number that the patient drew from a box. Before the beginning of chemotherapy, the mouth was examined by a trained last-year student, and all patients received oral health education on subjects including brushing and flossing. All patients (medication and placebo) took 10 g of powder. Oral examination of patients was performed in the beginning (day zero) and on the first, fourth, sixth, and tenth days. Mucositis was evaluated according to the Radiation Therapy Oncology Group (RTOG) criteria (zero=no erythema, 1=light red or pink erythema, 2=non-dark red, and 3=dark red). Also, the level of pain and burning in the mouth and throat were measured on all days of the study using the visual analogue scale (VAS). All obtained data were coded and analyzed by SPSS 24. Results: The present study was conducted on 39 patients who were undergoing chemotherapy (female=17 and male=22). On days three, seven, and ten of the study, only two subjects in the glutamine group were RTOG grade 1, and the rest of the group were grade 0. In the placebo group, only 2 subjects were grade 1 and the rest were grades 2 and 3. The mean duration of wound healing in the drug treatment group was 4.5±0.5 days, and its range was 3–9 days. Conclusion: Results showed that glutamine reduced pain and burning and the number of wounds. It also affected patients’ outcomes according to the RTOG criteria and improved patients’ symptoms.

Safety and Efficacy of L-Glutamine in Reducing the Frequency of Acute Complications Among Patients with Sickle Cell Disease: A Randomized Controlled Study

Abstract Introduction Patients with sickle cell disease (SCD) suffer from recurrent and unpredictable episodes of acute pain due to vaso-occlusive crisis (VOC) which may require hospitalization and they also develop chronic persistent pain. Since pain usually begins in infancy and continues throughout life, preventing the genesis of pain is comparatively higher than treating the pain once it has been evoked VOC represents the cause of almost 95% of hospitalizations for patients with SCD. L-glutamine is an amino acid needed for the synthesis of the pyridines for nucleotides, including nicotinamide adenine dinucleotide (NAD) and glutathione, in addition to glutamate, and becomes essential during oxidative stress exposure. The NADH: [NAD+ + NADH] (redox) ratio in sickle red blood cells (RBCs) is lower than in normal RBCs which is related to oxidative stress, so L-glutamine availability is important in SCD. Although the FDA-approved it for preventing acute complications in SCD, still has many gaps in our understanding of its therapeutic implications. Aim To evaluate the safety and efficacy of L-glutamine in reducing the number of VOCs in patients with SCD. Methods This is an investigator-initiated single-center phase 4 interventional randomized controlled trial at Ain Shams Pediatric Hematology Unit. Sixty SCD participants, their mean age was 9.2 ± 3.7 years, they were 35 males and 25 females, were randomly assigned in a 1:1 ratio to receive glutamine at a dose of 0.3 gm/kg/dose twice daily orally (up to a maximum of 15 g/dose) for 24 weeks or the standard of care (SOC) without glutamine intake. Results Thirty-seven (62%) had HbSS with 38% had other sickle cell variants. All participants were receiving HU therapy and were on stable dose during the last three months prior to enrollment. Almost half of the patients (48%) were on chelation therapy with deferasirox. Thirty SCD patients were recruited in each group either received glutamine or SOC, both groups were comparable as regards demographic data. All patients in both arms had VOCs in the last year more than two. For the primary endpoint, there was a decreasing trend in the number, severity, and hospitalization of VOC in the glutamine arm and there was a significantly lower cumulative number of VOCs in the glutamine group (38.9%) than SOC (52.8%) (p = 0.008) and lower cumulative number of hospitalizations (p < 0.001). Conclusion Glutamine reduced the number of VOCs and hospitalizations for VOC in our cohort with SCD.

Safety and efficacy of L-Glutamine in reducing the frequency of acute complications among patients with sickle cell disease: A randomized controlled study

To evaluate the safety and efficacy of L-glutamine in reducing vaso-occlusive crisis (VOC) and improving cerebral arterial blood flow in children with sickle cell disease (SCD). This is an interventional randomized controlled trial that recruited sixty SCD patients, aged 9.2 ± 3.7 years, who had at least two VOCs during the last 12 months and on a stable dose of hydroxyurea. They were randomly assigned in a 1:1 ratio to receive glutamine (0.3 gm/kg/dose/12h) orally for 24 weeks or the standard of care (SOC). All patients had VOCs in the last year > 3, those on glutamine had a higher number of VOCs and hospitalization for VOC in the last year. There was a decreasing trend in the number, severity, and hospitalization of VOC and a significantly lower cumulative number of VOCs and hospitalizations in the glutamine group than in SOC (p = 0.008, p < 0.001 respectively). Time-averaged mean maximum velocity for the glutamine group had a marginal increase in both middle cerebral arteries, all values remained normal within a normal range, and in both internal carotid arteries, values increased from abnormally low to normal ranges at week 24. Glutamine reduced the number of VOCs and severity and may have a potentially favorable impact on the cerebral arterial flow velocities.

The effect of enteral glutamine supplementation on T lymphocyte increase in a rat (Rattus norvegicus) model with thermal contact burns

Background: The common causes of death from burns are sepsis, infection, and multiorgan failure. Optimal immune cell function is crucial to prevent this condition. In this regard, T lymphocytes play a key role in the immune response to burns. Glutamine, an immunonutrition, serves as a main energy source for immune cells such as lymphocytes, macrophages, and fibroblasts. This study was conducted to understand the difference in T lymphocyte concentration in the tissue of contact thermal burns in control mice compared to mice given enteral glutamine. Methods: This study was an experimental study using a post-test randomized control design. Male mice were divided into 5 groups, each consisting of 5 mice. Contact thermal burns were created by placing a heated steel rod on the dorsal area of their heads for 4 seconds. Group I did not receive glutamine and was observed 1 hour after the burn. Groups II and III also did not receive glutamine but were observed on day 5 and day 10. Groups IV and V were given glutamine and observed on the same days. Subsequently, the T lymphocyte count was determined through microscopic examination. Results: Based on the analysis, there was no significant difference in the weight of the mice in all groups (p=0.130). In the control group, the T lymphocyte counts significantly varied between day 1, day 5, and day 10 (p=0.000), with no significant difference between day 5 and day 10 (p=0.410). Similar results were found in the glutamine group (p=0.000) but with no significant difference between day 5 and day 10 (p=0.158). The mean T lymphocyte count was significantly higher in the glutamine group on day 5 (p=0.007) and day 10 (p=0.006) compared to the control group. Conclusion: Enteral glutamine administration increases the number of T lymphocytes in damaged tissue due to thermal contact burns in mice.

Modification of a Selective NTRK2 Agonist and Confirmation of Activity in a Glaucoma-on-a-Chip Model.

RNYK is a selective agonist of the neurotrophic tyrosine kinase receptor type 2 (NTRK2) which has been screened from a phage-displayed peptide library. Its sequence is SGVYKVAYDWQH, similar to a native NTRK2 ligand, that is, brain-derived neurotrophic factor (BDNF). The current study was performed to recognize and confirm critical residues for RNYK activity in a glaucoma-on-a-chip model. We designed a modified RNYK (mRNYK) peptide based on hotspots of the RNYK sequence identified by alanine scanning. The critical residues consisted of tyrosine, valine, aspartic acid, and tryptophan (YVDW); however, lysine and glutamine were also maintained in the final sequence (YKVDWQ) for forming amide bonds and peptide dimerization. The affinity of mRNYK binding was confirmed by testing against NTRK2 receptors on the surface of ATRA-treated SH-SY5Y cells. The neuroprotective effect of mRNYK was also evaluated in cell culture after elevated pressure insult in a glaucoma-on-a-chip model. The primary amine on the lysine side-chain from one sequence (YKVDWQ) reacted with a γ-carboxamide group of glutamine from the other sequence, forming dimeric mRNYK. In silico, molecular dynamic simulations of the mRNYK-NTRK2 complex showed more stable and stronger interactions as compared to the RNYK-NTRK2 complex. In vitro, mRNYK demonstrated a neuroprotective effect on SH-SY5Y cells under normal and elevated pressure comparable to RNYK. The 50% effective concentration (logEC50) for mRNYK was 0.7009, which was better than RNYK with a logEC50 of 0.8318. The modified peptide studied herein showed improved stability over the original peptide (RNYK) and demonstrated potential for use as a BDNF agonist with neuroprotective properties for treatment of neurodegenerative disorders such as glaucoma.

Effectiveness of glutamine for the treatment of radiodermatitis in cancer patients: a meta-analysis of randomized controlled trials.

After receiving radiation therapy, 60%-95% of patients with cancer develop radiodermatitis, which causes pain, wound infection, and poor quality of life. Glutamine is a popular nutritional supplement for patients with cancer. Several studies examined the usefulness of glutamine for reducing radiodermatitis. However, there is still no consolidated evidence for clinical use. We searched PubMed, Embase, Cochrane Library, CINAHL PLUS, and the China Knowledge Resource Integrated Database for the relevant literature published up to March 2023, without language restrictions. Two reviewers screened, filtered, and appraised these articles independently, and their data were pooled using a random-effects model. Five randomized controlled trials (RCTs) with 218 participants were analyzed. The incidence of radiodermatitis in the glutamine group (89/110) was significantly lower than in the placebo group (99/108; risk ratio [RR], 0.90; 95% CI, 0.81-1.00; p = 0.05; I2 = 7%). The incidence of moderate to severe radiodermatitis was significantly lower in the glutamine group than in the placebo group (RR, 0.49; 95% CI, 0.32-0.76; p = 0.001; I2 = 52%). Moreover, subgroup analysis demonstrated heterogeneity (I2 = 52%) for moderate to severe radiodermatitis, the risk of which might be significantly reduced by a glutamine dose of 20-30g/day (RR, 0.60; 95% CI, 0.41-0.87; I2 = 0%). The meta-analysis indicate that glutamine might lead to a lower incidence of radiodermatitis, and that a glutamine dose of 20-30g/day might decrease the incidence of moderate to severe dermatitis. Thus, the serious impact of radiodermatitis on treatment follow-up makes the clinical use of glutamine even more important. PROSPERO number: CRD42021254394.

Glutamine Accelerates Post-Exercise Recovery of Arms Power, Leg Power, and Smash Velocity at 48 Hours for Non-Elite Badminton Athletes

Badminton is a sport that is characterized by long-lasting muscle contractions in continuous smash movements which lead to fatigue and glutamine can potentially reduce the incidence of muscle fatigue. The aim of the study is to investigate glutamine affecting post-exercise recovery in non-elite badminton athletes. It was a randomized group pre-test and post-test design. Twenty male students were involved and divided into 2 groups: The placebo (Plac) group was only given instruction for jumping smash activities and mineral water, while the glutamine (Glut) group was jumping smash activities and mineral water containing glutamine. The jumping smash activities were carried out in 10 sets with 20 repetitions with a rest period of 30 seconds per set. Glutamine was given 3 times after 1 hour of jumping smash activities, 24 hours, and 48 hours with a dose of 0.4 grams/KgBW. There were significant differences in the vertical jump, leg power, arm power, and smash velocity in pre-post-2 between the Placebo and Glutamine groups with p&lt;0.05. Meanwhile, no difference was observed in the vertical jump, leg power, arm power, and smash velocity (p&gt;0.05) between the Placebo and Glutamine groups 72 hours after the jumping smash activities (post 3). The administration of glutamine at a dose of 0.4 gram/Kg BW given three times post-jumping smash (eccentric) exercise can accelerate the 48-hour post-exercise recovery of vertical jump, arm power, leg power, and smash velocity. Badminton athletes who play matches daily are expected to consume glutamine to speed up recovery. Keywords: Glutamine; physical exercise; badminton; non-elite athletes

Effects of glutamine and omega-3 fatty acids on intestinal neomucosa formation on colon serosa in rats.

Intestinal neomucosa formation is a technique defined for the treatment of short bowel syndrome. This study evaluates the effect of glutamine and omega-3 fatty acids on the growth of intestinal neomucosa on the colonic serosal surface has been evaluated. Thirty-two adult male Sprague-Dawley rats were randomly divided into 4 groups: sham, control, glutamine, and omega-3. Laparotomy was performed on all groups. For rats other than the sham group, a 1-cm full-thickness incision was made 4 cm proximal to the ileocecal valve, and colonic serosal surface was sutured as a serosal patch over these openings. By using the oral gavage technique, the glutamine group was ingested with 200 mg/kg/day of glutamine, and the omega-3 group was ingested with 100 mg/kg/day of omega-3 fatty acids. At the end of 14 days, the rats were euthanized, blood specimens were collected, and intestinal segments, including serosal patches, were excised. Transforming growth factor-beta was significantly lower in the glutamine group compared to the control group. Similarly, fibroblast growth factor-2 was significantly lower in the glutamine group compared to the sham group. Intestinal neomucosa formation was observed in 100% of rats in the glutamine group. In the control and omega-3 groups, intestinal neomucosa formation was observed in 57.1% and 60% of rats, respectively. The inflammatory response, granulation tissue formation, and fibroblastic activity were more severe in the rats of the glutamine and omega-3 groups. The intestinal neomucosa formation is an experimental technique, and both glutamine and omega-3 fatty acids have the potential to positively affect inflammatory response, granulation tissue formation, and fibroblastic activity. Specifically, glutamine has a favorable effect on intestinal neomucosa formation.

Therapeutic Benefits of Tuna Oil by In Vitro and In Vivo Studies Using a Rat Model of Acetic Acid-Induced Ulcerative Colitis.

Ulcerative colitis (UC), an inflammation of the colon lining, represents the main form of inflammatory bowel disease IBD. Nutritional therapy is extremely important in the management of ulcerative colitis. Fish oil contains long-chain omega-3 polyunsaturated fatty acids, which have beneficial effects on health, including anti-inflammatory effects. This study aims to investigate the benefits of bluefin tuna oil extracted by the Soxhlet method in vitro by determining the anti-radical and anti-inflammatory activities and in vivo by evaluating the preventive and curative effects. The experiments were carried out using two doses of oil (100 and 260 mg/kg) and glutamine (400 and 1000 mg/kg) on the acetic acid-induced UC model. UC has been induced in Wistar rats by intrarectal administration of a single dose of 1 mL acetic acid (5% v/v in distilled water). The obtained results indicate that tuna oil and glutamine have a significant anti-free radical effect. Tuna oil has a marked anti-inflammatory power based on membrane stabilization and inhibiting protein denaturation. The reduction of various UC parameters, such as weight loss, disease activity score DAS, and colonic ulceration in rats pre-treated with tuna oil and glutamine, demonstrate that these treatments have a significant effect on UC. Total glutathione GSH, superoxide dismutase SOD, and catalase activities are significantly restored in the tuna oil and glutamine groups, while lipid peroxidation has been markedly reduced.

L-Glutamine and Survival of Patients with Locally Advanced Head and Neck Cancer Receiving Chemoradiotherapy.

We previously reported that L-glutamine reduces the severity of mucositis caused by chemoradiotherapy in patients with head and neck cancer. However, the impact of glutamine on the anti-tumor effect of chemoradiotherapy remains controversial. This study, which included 40 patients, investigated whether L-glutamine influences survival. Radiation therapy (total: 66 or 70 Gy), cisplatin, and docetaxel were co-administered for a period of 6 weeks. Patients were randomly assigned to receive either glutamine (glutamine group, n = 20) or placebo (placebo group, n = 20) during the entire course of chemoradiotherapy. We compared the overall survival and progression-free survival rates between the two groups. At 5-year follow-up, 16 (80%) and 13 (72%) patients in the glutamine and placebo groups, respectively, survived (with no significant difference in overall survival [glutamine group: 55.2 ± 12.7 months vs. placebo group: 48.3 ± 21.3 months]). A total of 14 (70%) and 12 (67%) patients in the glutamine and placebo groups, respectively, did not experience disease progression (with no significant difference in progression-free survival [glutamine group: 46.7 ± 19.5 months vs. placebo group: 43.6 ± 25.2 months]). These findings indicate that L-glutamine does not influence the survival of patients with locally advanced head and neck cancer receiving chemoradiotherapy.

Transglutaminase in Foods and Biotechnology.

Stabilization and reusability of enzyme transglutaminase (TGM) are important goals for the enzymatic process since immobilizing TGM plays an important role in different technologies and industries. TGM can be used in many applications. In the food industry, it plays a role as a protein-modifying enzyme, while, in biotechnology and pharmaceutical applications, it is used in mediated bioconjugation due to its extraordinary crosslinking ability. TGMs (EC 2.3.2.13) are enzymes that catalyze the formation of a covalent bond between a free amino group of protein-bound or peptide-bound lysine, which acts as an acyl acceptor, and the γ-carboxamide group of protein-bound or peptide-bound glutamine, which acts as an acyl donor. This results in the modification of proteins through either intramolecular or intermolecular crosslinking, which improves the use of the respective proteins significantly.

Glutamine alleviates Lipopolysaccharide-induced corneal epithelial inflammation and oxidative stress in dogs

Pseudomonas aeruginosa is a common pathogenic bacteria in canine ophthalmology. Lipopolysaccharide (LPS), a component in the cell wall of gram-negative bacteria, is released following bacterial lysis and causes pathology and inflammation of the cornea. Antibiotics are used to treat bacterial keratitis, and the reuse of antibiotics can easily cause bacterial resistance. Research has shown that glutamine (GLN) has anti-inflammatory and antioxidant biological functions. Herein, we explored the effects and underlying mechanisms of GLN and established an LPS-induced cornea inflammation model. Treatment groups comprised: control check (CK), LPS, LPS+GLN, and Sham groups. Topical GLN treatment alleviated corneal opacity, reduced corneal injury, and accelerated corneal wound healing. Furthermore, GLN treatment altered the uniform distribution of corneal epithelial cells and transformed the healing approach of these cells in the corneal wound from crawling to filling. The expression of Toll-like receptor 4 (TLR4), IL-6, TNF-α, and p-p65 and the activity of myeloperoxidase and superoxide dismutase decreased while the content of malondialdehyde increased in the LPS+GLN group compared with those in the LPS group. Thus, our study suggests that LPS-induced inflammation and oxidative stress may be suppressed via the TLR4/NF-κB signaling pathway by GLN and that GLN could be used as an adjunct therapy to reduce antibiotic use.

Enteral glutamine supplements for patients with severe burns: A systematic review and meta-analysis

Our previous study in 2009 concluded that glutamine may shorten the length of hospital stay (LOS) in patients with severe burns. Recent large-scale studies have suggested a decline in the effectiveness of glutamine in treating patients with severe burns over the last decade. Therefore, we conducted this systematic review and meta-analysis to update the status of glutamine uses in patients with severe burns. We retrieved related literature prior to December 2022 from the PubMed, Web of Science, Cochrane Library, Embase, SinoMed, Wanfang, and CNKI databases. Terms such as glutamine, enteral and burn were linked for searching. Adults patients with severe burns were included and non-randomized controlled trials were excluded. Data from studies that compared enteral glutamine for severe burns with a control group were extracted. The primary outcomes of mortality and infectious morbidities were pooled and analyzed. The modified Jadad scale and Cochrane collaboration's tool were used to assess the risk of bias in RCTs, and the Review Manager 5.4 was used to pool and analyze the data. Six randomized controlled trials involving 1398 patients were included in the analysis. There were no significant differences in overall mortality (risk ratio (RR)=0.37; 95% confidence interval (CI): 0.06-2.37; p=0.300) or infectious morbidities (RR=0.73; 95% CI: 0.41-1.31; p=0.290). The incidence of multiple organ dysfunction syndrome was similar between the 2 groups (RR=0.27; 95% CI: 0.03-2.24; p=0.220). The LOS (mean difference (MD)=-8.97; 95% CI:-15.22 to-2.71; p=0.005) and LOS/total burn surface area (MD=-0.27; 95% CI:-0.54 to 0.00; p=0.050) decreased in the enteral glutamine group. The incidence of wound infection was significantly reduced (RR=0.42; 95% CI: 0.16-1.06; p=0.070). Compared to the control group, enteral glutamine administration may not improve the mortality, although it may be associated with a shorter LOS, a lower LOS/total burn surface area ratio, and may reduce the risk of wound infection in patients with severe burns.

Spotlight in Plastic Surgery: April 2023.

Spotlight in Plastic Surgery: April 2023.

Postoperative parenteral glutamine supplementation improves the short-term outcomes in patients undergoing colorectal cancer surgery: A propensity score matching study.

The clinical utility of glutamine in patients undergoing colorectal cancer (CRC) surgery remains unclear. Therefore, we aimed to investigate the impact of postoperative treatment with glutamine on postoperative outcomes in patients undergoing CRC surgery. We included patients with CRC undergoing elective surgery between January 2014 and January 2021. Patients were divided into the glutamine and control groups. We retrospectively analyzed postoperative infections complications within 30 days and other outcomes using propensity score matching and performed between-group comparisons. We included 1,004 patients who underwent CRC surgeries; among them, 660 received parenteral glutamine supplementation. After matching, there were 342 patients in each group. The overall incidence of postoperative complications was 14.9 and 36.8% in the glutamine and control groups, respectively, indicating that glutamine significantly reduced the incidence of postoperative complications [p < 0.001; risk ratio (RR) 0.41 [95% CI 0.30-0.54]]. Compared with the control group, the glutamine group had a significantly lower postoperative infection complications rate (10.5 vs. 28.9%; p < 0.001; RR 0.36 [95% CI 0.26-0.52]). Although there was no significant between-group difference in the time to first fluid diet (p = 0.052), the time to first defecation (p < 0.001), first exhaust (p < 0.001), and first solid diet (p < 0.001), as well as hospital stay (p < 0.001) were significantly shorter in the glutamine group than in the control group. Furthermore, glutamine supplementation significantly reduced the incidence of postoperative intestinal obstruction (p = 0.046). Moreover, glutamine supplementation alleviated the decrease in albumin (p < 0.001), total protein (p < 0.001), and prealbumin levels (p < 0.001). Taken together, postoperative parenteral glutamine supplementation can effectively reduce the incidence of postoperative complications, promote the recovery of intestinal function, and improve albumin levels in patients undergoing CRC surgery.

Effect of Glutamine on Short-term Surgical Outcomes in Rectal Cancer Patients Receiving Neoadjuvant Therapy: A Propensity Score Matching Study

The effect of glutamine on postoperative complications and postoperative recovery in rectal cancer (RC) patients receiving neoadjuvant therapy (NT) is unclear. This study aimed to investigate the effects of intravenous glutamine supplementation on short-term postoperative outcomes in these patients. This retrospective study included patients with RC who received NT and underwent radical surgery between January 2013 and July 2022 and were either administered glutamine (glutamine group) or not administered glutamine (non-glutamine group). Propensity score matching method was used to analyze and compare postoperative complications and other outcome indicators. A total of 208 patients were reviewed, and 53 were included in each group post matching. While no significant difference in the time to first solid food intake between the two groups was observed, the glutamine group had a significantly reduced incidence of postoperative complications, shorter length of hospital stay, and shorter time to first defecation, first exhaust, and first fluid diet intake than those of the control group. Moreover, glutamine alleviated the reduction in albumin and prealbumin levels. Perioperative parenteral glutamine supplementation effectively reduces the incidence of postoperative complications, promotes postoperative recovery, and improves albumin levels in patients undergoing RC surgery and receiving NT.

Glutamine alleviated heat stress-induced damage of porcine intestinal epithelium associated with the mitochondrial apoptosis pathway mediated by heat shock protein 70.

The present study aimed to investigate the effect of glutamine (Gln) addition on the damage of porcine intestinal epithelial cells (IPEC-J2) induced by heat stress (HS). IPEC-J2 cultured in logarithmic growth period in vitro were firstly exposed to 42 °C for 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 h for cell viability and cultured with 1, 2, 4, 6, 8, or 10 mmol Gln per L of culture media for heat shock protein 70 (HSP70) expression to determine the optimal disposal strategy (HS, 42 °C for 12 h and HSP70 expression, 6 mmol/L Gln treatment for 24 h). Then IPEC-J2 cells were divided into three groups: control group (Con, cultured at 37 °C), HS group (HS, cultured at 42 °C for 12 h), and glutamine group (Gln+HS, cultured at 42 °C for 12 h combined with 6 mmol/L Gln treatment for 24 h). The results showed that HS treatment for 12 h significantly decreased the cell viability of IPEC-J2 (P < 0.05) and 6 mmol/L Gln treatment for 12 h increased HSP70 expression (P < 0.05). HS treatment increased the permeability of IPEC-J2, evidenced by the increased fluorescent yellow flux rates (P < 0.05) and the decreased transepithelial electrical resistance (P < 0.05). Moreover, the downregulated protein expression of occludin, claudin-1, and zonula occludens-1 was observed in HS group (P < 0.05), but Gln addition alleviated the negative effects on permeability and the integrity of intestinal mucosal barrier induced by HS (P < 0.05). In addition, HS resulted in the elevations in HSP70 expression, cell apoptosis, cytoplasmic cytochrome c potential expression, and the protein expressions of apoptosis-related factors (apoptotic protease-activating factor-1, cysteinyl aspartate-specific proteinase-3, and cysteinyl aspartate-specific proteinase-9) (P < 0.05); however, the reductions in mitochondrial membrane potential expression and B-cell lymphoma-2 expression were induced by HS (P < 0.05). But Gln treatment attenuated HS-induced adverse effects mentioned above (P < 0.05). Taken together, Gln treatment exhibited protective effects in protecting IPEC-J2 from cell apoptosis and the damaged integrity of epithelial mucosal barrier induced by HS, which may be associated with the mitochondrial apoptosis pathway mediated by HSP70.

Science, Medicine, and the Anesthesiologist

Science, Medicine, and the Anesthesiologist

Glutamine supplementation attenuates intestinal apoptosis by inducing heat shock protein 70 in heatstroke rats.

Heatstroke is the most hazardous heat-related illness and has a high fatality rate. We investigated whether glutamine supplementation could have a protective effect on heatstroke rats. Twenty-five 12-week-old male Wistar rats (weight 305±16 g) were randomly divided into a control group (n=5), heatstroke (HS) group (n=10), and heatstroke+glutamine (HSG) group (n=10). Seven days before heat exposure, glutamine (0.4 g/[kg·d]) was administered to the rats in the HSG group by gavage every day. Three hours after heat exposure, serum samples were collected to detect white blood cells, coagulation indicators, blood biochemical indicators, and inflammatory cytokines in the rats. The small intestine tissue was stained to analyze pathological structural changes and apoptosis. Finally, immunohistochemistry and Western blotting were used to analyze the expression levels of heat shock protein 70 (HSP70). Multiple comparisons were analyzed by using one-way analysis of variance, and the Bonferroni test was conducted for the post hoc comparisons. After heat exposure, the core temperature of the HS group (40.65±0.31 °C) was higher than the criterion of heatstroke, whereas the core temperature of the HSG group (39.45±0.14 °C) was lower than the criterion. Glutamine supplementation restored the increased white blood cells, coagulation indicators, blood biochemical indicators, and inflammatory cytokines that were induced by heatstroke to normal levels. The intestinal mucosa was injured, and the structure of tight junctions was damaged in the HS group; however, the structure of intestinal mucosal epithelial cells was stable in the HSG group. Glutamine supplementation alleviated intestinal apoptosis and up-regulated HSP70 expression. Glutamine supplementation may alleviate intestinal apoptosis by inducing the expression of HSP70 and have a protective effect on heatstroke rats.

Effect of Glutamine Administration After Cardiac Surgery on Kidney Damage in Patients at High Risk for Acute Kidney Injury: A Randomized Controlled Trial.

Acute kidney injury (AKI) is a common complication after cardiac surgery and is associated with increased morbidity and mortality. However, no specific treatment options are available, emphasizing the need for preventive measures. The aim of this study was to clarify the effect of glutamine on [TIMP2]*[IGFBP7] levels at the end of the intervention period. In a randomized clinical, double-blind pilot study, 64 eligible cardiac surgery patients at high risk for AKI identified by high urinary [TIMP2]*[IGFBP7] were randomized, and body weight-adapted intravenous glutamine or saline-control was administered continuously for 12 hours postoperatively. The primary outcome was urinary [TIMP2]*[IGFBP7] at the end of the 12-hour study period. Secondary outcomes included kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) at 12 hours, overall AKI rates at 72 hours, free days through day 28 of mechanical ventilation and vasoactive medication, renal recovery at day 90, requirement of renal replacement therapy and mortality each at days 30, 60, and 90, length of intensive care unit (ICU) and hospital stay, and major adverse kidney events consisting of mortality, dialysis dependency, and persistent renal dysfunction (serum creatinine ≥2× compared to baseline value) at day 90 (major adverse kidney event; MAKE 90 ). Sixty-four patients (mean age, 68.38 [standard deviation {SD} ± 10.48] years; 10 of 64 women) were enrolled and randomized. Patients received coronary artery bypass graft surgery (32/64), valve surgery (18/64), coronary artery bypass graft and valve surgery (6/64), or other procedures (8/64). Mean on-pump time was 68.38 (standard deviation ± 10.48) minutes. After glutamine administration, urinary [TIMP-2]*[IGFBP7] was significantly lower in the glutamine compared to the control group (primary end point, intervention: median, 0.18 [Q1, Q3; 0.09, 0.29], controls: median, 0.44 [Q1, Q3; 0.14, 0.79]; P = .01). In addition, [KIM-1] and [NGAL] were also significantly lower in the glutamine group. The overall AKI rate within 72 hours was not different among groups: (intervention 11/31 [35.5%] versus control 8/32 [25.0%]; P = .419; relative risk [RR], 0.86% [95% confidence interval {CI}, 0.62-1.20]). There were no differences regarding secondary end points. Glutamine significantly decreased markers of kidney damage in cardiac surgery patients at high risk for AKI. Future trials have to be performed to investigate whether the administration of glutamine might be able to reduce the occurrence of AKI after cardiac surgery.