Oral supplementations with free and dipeptide forms of L-glutamine in endotoxemic mice: effects on muscle glutamine-glutathione axis and heat shock proteins

Sepsis is a leading cause of death in intensive care units worldwide. Low availability of glutamine contributes to the catabolic state of sepsis. l-Glutamine supplementation has antioxidant properties and modulates the expression of heat shock proteins (HSPs). This study investigated the effects of...

Full description

Bibliographic Details
Main Authors: Cruzat, Vinicius, Pantaleao, L., Donato Jr, J., de Bittencourt Jr, P., Tirapegui, J.
Format: Journal Article
Published: Elsevier Inc 2014
Subjects:
Online Access:http://hdl.handle.net/20.500.11937/34658
_version_ 1848754283065901056
author Cruzat, Vinicius
Pantaleao, L.
Donato Jr, J.
de Bittencourt Jr, P.
Tirapegui, J.
author_facet Cruzat, Vinicius
Pantaleao, L.
Donato Jr, J.
de Bittencourt Jr, P.
Tirapegui, J.
author_sort Cruzat, Vinicius
building Curtin Institutional Repository
collection Online Access
description Sepsis is a leading cause of death in intensive care units worldwide. Low availability of glutamine contributes to the catabolic state of sepsis. l-Glutamine supplementation has antioxidant properties and modulates the expression of heat shock proteins (HSPs). This study investigated the effects of oral supplementation with l-glutamine plus l-alanine (GLN+ALA), both in the free form and l-alanyl-l-glutamine dipeptide (DIP), on glutamine-glutathione (GSH) axis and HSPs expression in endotoxemic mice. B6.129F2/J mice were subjected to endotoxemia (lipopolysaccharides from Escherichia coli, 5 mg.kg−1, LPS group) and orally supplemented for 48 h with either l-glutamine (1 g.kg−1) plusl-alanine (0.61 g.kg−1) (GLN+ALA-LPS group) or 1.49 g.kg−1 of DIP (DIP-LPS group). Endotoxemia reduced plasma and muscle glutamine concentrations [relative to CTRL group] which were restored in both GLN+ALA-LPS and DIP-LPS groups (P<.05). In supplemented groups were re-established GSH content and intracellular redox status (GSSG/GSH ratio) in circulating erythrocytes and muscle. Thiobarbituric acid reactive substance was 4-fold in LPS treated mice relative to the untreated CTRL group, and plasma TNF-α and IL-1β levels were attenuated by the supplements. Heat shock proteins 27, 70 and 90 (protein and mRNA) were elevated in the LPS group and were returned to basal levels (relative to CTRL group) in both GLN+ALA-LPS and DIP-LPS groups. Supplementations to endotoxemic mice resulted in up-regulation of GSH reductase, GSH peroxidase and glutamate cysteine ligase mRNA expression in muscle. In conclusion, oral supplementations with GLN+ALA or DIP are effective in reversing the conditions of LPS-induced deleterious impact on glutamine-GSH axis in mice under endotoxemia.
first_indexed 2025-11-14T08:37:57Z
format Journal Article
id curtin-20.500.11937-34658
institution Curtin University Malaysia
institution_category Local University
last_indexed 2025-11-14T08:37:57Z
publishDate 2014
publisher Elsevier Inc
recordtype eprints
repository_type Digital Repository
spelling curtin-20.500.11937-346582017-09-13T16:07:21Z Oral supplementations with free and dipeptide forms of L-glutamine in endotoxemic mice: effects on muscle glutamine-glutathione axis and heat shock proteins Cruzat, Vinicius Pantaleao, L. Donato Jr, J. de Bittencourt Jr, P. Tirapegui, J. Glutamine Sepsis Alanine Oxidative stress HSPs GSH Sepsis is a leading cause of death in intensive care units worldwide. Low availability of glutamine contributes to the catabolic state of sepsis. l-Glutamine supplementation has antioxidant properties and modulates the expression of heat shock proteins (HSPs). This study investigated the effects of oral supplementation with l-glutamine plus l-alanine (GLN+ALA), both in the free form and l-alanyl-l-glutamine dipeptide (DIP), on glutamine-glutathione (GSH) axis and HSPs expression in endotoxemic mice. B6.129F2/J mice were subjected to endotoxemia (lipopolysaccharides from Escherichia coli, 5 mg.kg−1, LPS group) and orally supplemented for 48 h with either l-glutamine (1 g.kg−1) plusl-alanine (0.61 g.kg−1) (GLN+ALA-LPS group) or 1.49 g.kg−1 of DIP (DIP-LPS group). Endotoxemia reduced plasma and muscle glutamine concentrations [relative to CTRL group] which were restored in both GLN+ALA-LPS and DIP-LPS groups (P<.05). In supplemented groups were re-established GSH content and intracellular redox status (GSSG/GSH ratio) in circulating erythrocytes and muscle. Thiobarbituric acid reactive substance was 4-fold in LPS treated mice relative to the untreated CTRL group, and plasma TNF-α and IL-1β levels were attenuated by the supplements. Heat shock proteins 27, 70 and 90 (protein and mRNA) were elevated in the LPS group and were returned to basal levels (relative to CTRL group) in both GLN+ALA-LPS and DIP-LPS groups. Supplementations to endotoxemic mice resulted in up-regulation of GSH reductase, GSH peroxidase and glutamate cysteine ligase mRNA expression in muscle. In conclusion, oral supplementations with GLN+ALA or DIP are effective in reversing the conditions of LPS-induced deleterious impact on glutamine-GSH axis in mice under endotoxemia. 2014 Journal Article http://hdl.handle.net/20.500.11937/34658 10.1016/j.jnutbio.2013.11.009 Elsevier Inc restricted
spellingShingle Glutamine
Sepsis
Alanine
Oxidative stress
HSPs
GSH
Cruzat, Vinicius
Pantaleao, L.
Donato Jr, J.
de Bittencourt Jr, P.
Tirapegui, J.
Oral supplementations with free and dipeptide forms of L-glutamine in endotoxemic mice: effects on muscle glutamine-glutathione axis and heat shock proteins
title Oral supplementations with free and dipeptide forms of L-glutamine in endotoxemic mice: effects on muscle glutamine-glutathione axis and heat shock proteins
title_full Oral supplementations with free and dipeptide forms of L-glutamine in endotoxemic mice: effects on muscle glutamine-glutathione axis and heat shock proteins
title_fullStr Oral supplementations with free and dipeptide forms of L-glutamine in endotoxemic mice: effects on muscle glutamine-glutathione axis and heat shock proteins
title_full_unstemmed Oral supplementations with free and dipeptide forms of L-glutamine in endotoxemic mice: effects on muscle glutamine-glutathione axis and heat shock proteins
title_short Oral supplementations with free and dipeptide forms of L-glutamine in endotoxemic mice: effects on muscle glutamine-glutathione axis and heat shock proteins
title_sort oral supplementations with free and dipeptide forms of l-glutamine in endotoxemic mice: effects on muscle glutamine-glutathione axis and heat shock proteins
topic Glutamine
Sepsis
Alanine
Oxidative stress
HSPs
GSH
url http://hdl.handle.net/20.500.11937/34658