Glutamine-Enriched Total Parenteral Nutrition Enhances Plasma Glutathione in the Resting State

doi:10.1006/jsre.1996.0077

Journal of Surgical Research

Volume 61, Issue 1, 15 February 1996, Pages 35-38

https://doi.org/10.1006/jsre.1996.0077 Get rights and content

Abstract

Glutathione (GSH) is the major intracellular antioxidant and is essential to normal cell function and replication. Cysteine and other thiol compounds have been considered rate-limiting for GSH biosynthesis, but recent studies have demonstrated that glutamine (GLN) becomes essential during metabolic stress to replete tissue GSH levels which have become depleted. To determine the role of GLN supplementation in the resting, nonstressed state, we studied three groups of Wistar rats. The animals were catheterized and randomly assigned to one of three groups: (1) chowad libitumgroup receiving iv saline (control), (2) standard total parenteral nutrition (STA-TPN) group, and (3) glutamine-enriched TPN (GLN-TPN) group. The intravenously fed animals received no rat chow. The infusions were administered at a rate of 2.2 ml/hr for 4 days and all animals were harvested on the fifth day of study. The GLN-TPN group had a significantly higher plasma GSH level than STA-TPN or control animals (P< 0.01). The hepatic concentration of GSH and the oxidized GSH/reduced GSH were similar in all groups. GLN-TPN had a significantly lower plasma ALT level than the control group (P< 0.05). The control group had a significantly higher ALP level than STA-TPN and GLN-TPN animals (P< 0.01). There were no significant differences in other measures of hepatic functions among the three groups. Our data demonstrate that in this model GLN-enriched TPN enhances plasma GSH concentrations, while maintaining hepatic GSH stores. This suggests that GSH turnover is altered during glutamine-enriched TPN, which may explain how dietary GLN supplementation enhances tissue antioxidant capacity.

References (0)

Cited by (58)

Characterization and function of mandarin fish c-Myc during viral infection process
2022, Fish and Shellfish Immunology
Citation Excerpt :
Normally, glucose is considered to be the main source of ATP production in the cell via glycolysis and the tricarboxylic acid (TCA) cycle. However, the glucose metabolism remodeling in virus-infected cells results in glucose metabolism entering into the aerobic glycolysis pathway to produce lactic acid, rather than entering the TCA cycle [9,10]. Meanwhile, glutamine has often been shown to reload the TCA cycle via α-ketoglutaric acid (α-KG), a process termed as glutaminolysis [11].
c-Myc is a transcription factor and master regulator of cellular metabolism, and plays a critical role in virus replication by regulating glutamine metabolism. In this study, the open-reading frame (ORF) of c-Myc, designated as Sc-c-Myc, was cloned and sequenced. Multiple alignment of the amino acid sequence showed that the conserved domain of Sc-c-Myc, including the helix–loop–helix-zipper (bHLHzip) domain and Myc N-terminal region, shared high identities with other homologues from different species. Sc-c-Myc mRNA was widely expressed in the examined tissues of mandarin fish, and the higher mRNA levels was expressed in hind kidney. Moreover, mRNA and protein level of Sc-c-Myc was significantly increased in the Chinese perch brain (CPB) cells and spleen of mandarin fish post infection with infectious spleen and kidney necrosis virus (ISKNV) and Siniperca chuatsi rhabdovirus (SCRV). Sc-c-Myc overexpression promoted ISKNV and SCRV replication, on the contrary, knocking down Sc-c-Myc restrained ISKNV and SCRV replication. These results indicated that Sc-c-Myc involved in ISKNV and SCRV replication and proliferation, providing a potential target for the development of new therapic strategy against ISKNV and SCRV.
Quantitation of the glutathione in human peripheral blood by matrix-assisted laser desorption ionization time-of-flight mass spectrometry coupled with micro-scale derivatization
2011, Analytica Chimica Acta
Citation Excerpt :
Cysteine is generally considered to be the rate-limiting substrate for the formation of GSH, so reducing the intake of protein may decrease the synthesis of GSH [50]. Moreover, supplementation in the clinical diet can be used to maintain high levels of glutathione and to avoid oxidative stress damage [51,52]. GSH aids in the protection of cells against toxicants and in the metabolism of endogenous and xenobiotic compounds [53–55].
Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been broadly applied to analyze high-molecular-weight compound (such as polymer or proteomic research) but seldom used for low-molecular-weight compound analysis. The objective of this study is the development of a simple analytical method for the determination of the concentration of tripeptide glutathione (GSH) by MALDI-TOF MS. Unfortunately, GSH could not be detected directly by MALDI-TOF MS. Our method is based on the derivatization of GSH with 4-bromomethyl-6,7-dimethoxycoumarin (BrDMC) in acetonitrile using potassium hydroxide (KOH) as a base catalyst. After simple extraction step, the supernatant is spotted on a target plate, mixed with matrix α-cyano-4-hydroxycinnamic acid (CHCA) and then detected by MALDI-TOF MS.
Some parameters affecting the derivatization of GSH were investigated, such as the concentration of BrDMC, KOH, different base catalyst, and reaction time, etc. The regression equations of GSH derivative possessed good linearity (r ≧ 0.995) over the range of 1.0–100.0 μM. The relative standard deviation (R.S.D.) and relative error (R.E.) values in intra- and inter-day assays were below 13%, which showed good precision and accuracy. This proposed method was successfully applied to monitor the concentration of GSH in human blood at micro-scale level.
Effect of exclusive enteral nutritional treatment on plasma antioxidant concentrations in childhood Crohn's disease
2007, Clinical Nutrition
Citation Excerpt :
A decrease in glutathione concentration has been described in intestinal tissues of patients with CD.23 Glutamine infusion has been shown to increase both intestinal mucosal24 and plasma25 glutathione concentrations in experimental animals. In the present study, glutamine supplementation of an enteral diet did not increase the concentrations of whole blood glutathione in children with active CD.
Oxidative stress and depletion of antioxidants may play a role in the pathogenesis of Crohn's disease (CD). The aim of this study was to determine the effect of exclusive enteral nutrition, which is increasingly being used as primary therapy for CD, on plasma antioxidant concentrations in children with active CD.
In a double-blind randomised controlled trial, 15 children with active CD (mean age, 11.3 years, range 6.8–15.7) attending a paediatric gastroenterology referral centre, were assigned to receive either a standard polymeric diet (Group S, n=8) or a glutamine-enriched polymeric diet (Group G, n=7) as primary therapy for active CD. Plasma concentrations of selenium, urates, vitamin A, vitamin E, vitamin C, glutathione, and also malondialdehyde (MDA) were measured at baseline and after 4 weeks of exclusive enteral nutritional treatment.
Mean (95% CI) selenium concentration of the cohort increased significantly from 0.82 μmol/l (0.72, 0.91) to 1.14 μmol/l (0.98, 1.3), P<0.001. There were, however, significant reductions in mean concentrations of vitamin C {11.8 mg/l (7.7, 15.8) to 6.5 mg/l (4.5, 8.7), P=0.01} and vitamin E {11.3 mg/l (10.3, 12.4) to 9.4 mg/l (8.7, 10.1), P=0.03}. The concentrations of vitamin A, urates, glutathione and MDA did not change significantly over the study period. Glutamine supplementation did not have any significant effect on plasma antioxidant concentrations.
Significant changes in circulating antioxidant concentrations occurred in children with active CD receiving exclusive enteral nutritional treatment. Glutamine supplementation was not beneficial in improving plasma antioxidant status.
No evidence for oxidative stress in patients on home parenteral nutrition
2006, Clinical Nutrition
Patients on total parenteral nutrition depend on the composition of the nutritional formulation for maintenance of their oxidant–antioxidant balance. The present observational study was conducted to evaluate a substantial part of our patient population for evidence of oxidative stress.
Venous blood samples were obtained from 41 patients on home parenteral nutrition (HPN) and 41 healthy controls. Glutathione in plasma and whole blood, glutathione peroxidase and superoxide dismutase in erythrocytes and total plasma antioxidant capacity were measured to assess the antioxidant status. Oxidant status was evaluated by measuring the production of reactive oxygen species by leukocytes. Oxidative damage was assessed by measuring lipid peroxidation and protein oxidation products.
Patients on HPN showed some signs of increased oxidative stress, however, there were no signs for oxidative damage, compared with healthy controls. In addition, activity of any underlying disease was not associated with increased oxidative stress.
The current treatment regime for patients on HPN at our center apparently prevents the development of significant oxidative damage, despite signs of some oxidative stress. Based on these data, adaptations in the composition of parenteral nutritional formulations do not seem mandatory.
Why should a single nutrient - Glutamine - Improve outcome? The remarkable story of glutamine dipeptides
2004, Clinical Nutrition, Supplement
Citation Excerpt :
In a current report, parenteral glutamine promoted growth of the remnant liver in malnourished rats after partial hepatectomy, and maintained hepatic morphology after surgery.107 Recent reports emphasize that supplemental glutamine preserves hepatic and intestinal stores of glutathione and maintains plasma concentrations.108–110 Experimental feeding with glutamine resulted in a considerable increase in gut fractional uptake and a marked increase in intestinal glutathione fractional release,111 suggesting increased intestinal glutathione production.
Recent knowledge about efficient utilization of intravenously supplied dipeptides has made it possible to supplement available amino acids solutions with stable, highly soluble glutamine-containing dipeptides. This novel approach has opened up a new dimension: today, glutamine-containing dipeptides are an integral part of the routine in clinical practice. In numerous controlled clinical trials it could be convincingly demonstrated that supplemental glutamine (dipeptide) nutrition was associated with improved nitrogen balance and mood; increased protein synthesis and lymphocyte count (total and subpopulation); maintained intestinal function; intracellular muscle free glutamine pool; gut permeability and function; and reduced 3-MeHis excretion. More importantly it could be demonstrated that glutamine (dipeptide) supplementation reduced the rate of infectious complications, length of hospital stay and mortality.
Stable glutamine containing dipeptides introduced a new dimension in clinical glutamine research; at present these dipeptides are integral parts of routine clinical practice.
Metabolic, antioxidant, nutraceutical, probiotic, and herbal therapies relating to the management of hepatobiliary disorders
2004, Veterinary Clinics of North America - Small Animal Practice

View all citing articles on Scopus

View full text

Regular ArticleGlutamine-Enriched Total Parenteral Nutrition Enhances Plasma Glutathione in the Resting State

Abstract

Regular Article
Glutamine-Enriched Total Parenteral Nutrition Enhances Plasma Glutathione in the Resting State