Short-term glutamine supplementation decreases lung inflammation and the receptor for advanced glycation end-products expression in direct acute lung injury in mice

Chuang, Yin-Ching; Shaw, Huey-Mei; Chen, Chi‐Chung; Pan, He-Jia; Lai, Wei–Chih; Huang, Hui-Ling

doi:10.1186/1471-2466-14-115

Cited by 9 publications

(6 citation statements)

References 40 publications

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“…Two and 18 h after induction of lung injury, glutamine prevented morphological changes in the lung parenchyma and neutrophil infiltration in the alveolar space, enhanced reduced glutathione (GSH) synthesis, attenuated interleukin (IL)-8 release in lung tissue, and prevented higher CD11b expression in blood neutrophils [ 53 ]. Another study performed in mice fed a glutamine-supplemented diet (0.8 g/kg body weight from feed conversion) 10 days before intratracheal administration of hydrochloric acid plus E. coli LPS-induced ARDS showed that glutamine pretreatment reduced levels of the receptor for advanced glycation end-products (RAGE) and interleukin (IL)-1β in bronchoalveolar lavage fluid (BALF), with corresponding decreases in mRNA expression [ 54 ]. In a two-hit model of hydrochloric acid aspiration plus injurious mechanical ventilation, intravenous glutamine, administered 30 min before the randomization for recruitment maneuver and soon after inducing acid aspiration, improved lung morphofunction as well as neutrophil recruitment and cytokine production in lung tissue [ 55 ].…”

Section: Glutamine Therapy In Respiratory Diseasesmentioning

confidence: 99%

Exogenous Glutamine in Respiratory Diseases: Myth or Reality?

et al. 2016

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Several respiratory diseases feature increased inflammatory response and catabolic activity, which are associated with glutamine depletion; thus, the benefits of exogenous glutamine administration have been evaluated in clinical trials and models of different respiratory diseases. Recent reviews and meta-analyses have focused on the effects and mechanisms of action of glutamine in a general population of critical care patients or in different models of injury. However, little information is available about the role of glutamine in respiratory diseases. The aim of the present review is to discuss the evidence of glutamine depletion in cystic fibrosis (CF), asthma, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), and lung cancer, as well as the results of exogenous glutamine administration in experimental and clinical studies. Exogenous glutamine administration might be beneficial in ARDS, asthma, and during lung cancer treatment, thus representing a potential therapeutic tool in these conditions. Further experimental and large randomized clinical trials focusing on the development and progression of respiratory diseases are necessary to elucidate the effects and possible therapeutic role of glutamine in this setting.

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Section: Glutamine Therapy In Respiratory Diseasesmentioning

confidence: 99%

Exogenous Glutamine in Respiratory Diseases: Myth or Reality?

et al. 2016

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“…Here, we tested the hypothesis that 4% glutamine supplementation in mice with SSADHD would be therapeutically beneficial via restoration of brain neurotransmitter homeostasis. 4% glutamine supplementation has been shown to promote rescuing effects in several mouse models . Since low glutamine levels were reported as early as post‐natal day of life (P) 3, we postulated that glutamine deficiency occurred already during fetal life and chose to begin supplementation during the prenatal period via maternal supplementation, with continuation throughout weaning and until P30.…”

Section: Introductionmentioning

confidence: 99%

“…4% glutamine supplementation has been shown to promote rescuing effects in several mouse models. [6][7][8] Since low glutamine levels were reported as early as post-natal day of life (P) 3, 2 we postulated that glutamine deficiency occurred already during fetal life and chose to begin supplementation during the prenatal period via maternal supplementation, with continuation throughout weaning and until P30. Prenatal supplementation of nutrients and other amino acids has proven to be effective in other animal studies in the literature.…”

Section: Introductionmentioning

confidence: 99%

Maternal glutamine supplementation in murine succinic semialdehyde dehydrogenase deficiency, a disorder of γ‐aminobutyric acid metabolism

Brown

Walters

Schmidt

et al. 2019

J of Inher Metab Disea

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Murine succinic semialdehyde dehydrogenase deficiency (SSADHD) manifests with high concentrations of γ‐aminobutyric acid (GABA) and γ‐hydroxybutyrate (GHB) and low glutamine in the brain. To understand the pathogenic contribution of central glutamine deficiency, we exposed aldh5a1−/− (SSADHD) mice and their genetic controls (aldh5a1+/+) to either a 4% (w/w) glutamine‐containing diet or a glutamine‐free diet from conception until postnatal day 30. Endpoints included brain, liver and blood amino acids, brain GHB, ataxia scores, and open field testing. Glutamine supplementation did not improve aldh5a1−/− brain glutamine deficiency nor brain GABA and GHB. It decreased brain glutamate but did not change the ratio of excitatory (glutamate) to inhibitory (GABA) neurotransmitters. In contrast, glutamine supplementation significantly increased brain arginine (30% for aldh5a1+/+ and 18% for aldh5a1−/− mice), and leucine (12% and 18%). Glutamine deficiency was confirmed in the liver. The test diet increased hepatic glutamate in both genotypes, decreased glutamine in aldh5a1+/+ but not in aldh5a1−/−, but had no effect on GABA. Dried bloodspot analyses showed significantly elevated GABA in mutants (approximately 800% above controls) and decreased glutamate (approximately 25%), but no glutamine difference with controls. Glutamine supplementation did not impact blood GABA but significantly increased glutamine and glutamate in both genotypes indicating systemic exposure to dietary glutamine. Ataxia and pronounced hyperactivity were observed in aldh5a1−/− mice but remained unchanged by the diet intervention. The study suggests that glutamine supplementation improves peripheral but not central glutamine deficiency in experimental SSADHD. Future studies are needed to fully understand the pathogenic role of brain glutamine deficiency in SSADHD.

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“…In the field of acute lung injury, a few studies have shown a beneficial effect of Gln supplementation 26,27 , while others have deemed Gln inhibition to be important for preventing progression following injury 28 . In the case of TB, Mtb infection has been shown to induce glutamine metabolism transcripts 29,30 .…”

Section: Discussionmentioning

confidence: 99%

Glutamine metabolism inhibition has dual immunomodulatory and antibacterial activities againstMycobacterium tuberculosis

Parveen¹,

Shen²,

Lun³

et al. 2023

Preprint

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As one of the most successful human pathogens, Mycobacterium tuberculosis (Mtb) has evolved a diverse array of determinants to subvert host immunity and alter host metabolic patterns. However, the mechanisms of pathogen interference with host metabolism remain poorly understood. Here we show that a novel glutamine metabolism antagonist, JHU083, inhibits Mtb proliferation in vitro and in vivo. JHU083-treated mice exhibit weight gain, improved survival, a 2.5 log lower lung bacillary burden at 35 days post-infection, and reduced lung pathology. JHU083 treatment also initiates earlier T-cell recruitment, increased proinflammatory myeloid cell infiltration, and a reduced frequency of immunosuppressive myeloid cells when compared to uninfected and rifampin-treated controls. Metabolomics analysis of lungs from JHU083-treated Mtb-infected mice revealed reduced glutamine levels, citrulline accumulation suggesting elevated NOS activity, and lowered levels of quinolinic acid which is derived from the immunosuppressive metabolite kynurenine. When tested in an immunocompromised mouse model of Mtb infection, JHU083 lost its therapeutic efficacy suggesting the drug host-directed effects are likely to be predominant. Collectively, these data reveal that JHU083-mediated glutamine metabolism inhibition results in dual antibacterial and host-directed activity against tuberculosis.

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Short-term glutamine supplementation decreases lung inflammation and the receptor for advanced glycation end-products expression in direct acute lung injury in mice

Cited by 9 publications

References 40 publications

Exogenous Glutamine in Respiratory Diseases: Myth or Reality?

Exogenous Glutamine in Respiratory Diseases: Myth or Reality?

Maternal glutamine supplementation in murine succinic semialdehyde dehydrogenase deficiency, a disorder of γ‐aminobutyric acid metabolism

Glutamine metabolism inhibition has dual immunomodulatory and antibacterial activities againstMycobacterium tuberculosis

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