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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The content of ammonia, glutamine, dicarboxylic amino acids and GABA was studied in the brain under 1, 2, 4-fold separate and simultaneous effect of hypothermia (19-20 C) and hyperoxia (3 atm.). A two-fold hypothermia of rats is accompanied by a greater increase of ammonia in the brain than a three-fold one. The content of glutamine under two-fold cooling is unchanged and under three-fold cooling it is twice as low as compared to its content in the brain of the control rats. The content of glutamic acid decreased after two-fold hypothermia is almost unchanged by the third seance of hypothermia. The repeated actions of hyperoxia also cause a considerable increase in the ammonia content but the dynamics of changes in the content of the nitrogenous metabolic products is contary to that in animals subjected to repeated seances of hypothermia. A simultaneous combined action of hypothermia and hyperoxia produces no additive effect on the system ammonia-glutaminic acid.
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PMID:[Effect of hypothermia and hyperoxia on the ammonia-glutamic acid system in the brain of rats]. 96 Feb 39

Cellular intoxication by elevated concentrations of O2 may be considered as a model for accelerated cellular aging processes resulting from excessive free radical production by normal metabolic pathways. We describe here that exposure of HeLa cell cultures to 80% O2 for 2 days causes progressive growth inhibition and loss of reproductive capacity. This intoxication was correlated with inhibition of cellular O2 consumption and inactivation of 3 mitochondrial flavoproteins, i.e., partial inactivation of NADH and succinate dehydrogenases and total inactivation of alpha-ketoglutarate dehydrogenase. As alpha-ketoglutarate dehydrogenase controls the influx of glutamine/glutamate into the Krebs cycle, which is the major pathway for oxidative ATP generation in HeLa cells, the inactivation of alpha-ketoglutarate dehydrogenase was expectedly correlated with a net fall in glutamine/glutamate utilization. Furthermore, a simultaneous increase in glucose consumption and lactate production was observed, indicating that the cellular response to respiratory failure is to generate more ATP from glycolysis. In spite of this response, extensive depletion of ATP was observed. Thus, hyperoxia-induced growth inhibition and loss of clonogenicity seem to be due primarily to an impairment of mitochondrial energy metabolism resulting from inactivation of SH-group-containing flavoprotein enzymes localized at or near the inner mitochondrial membrane. These observations may be relevant for theories implicating loss of mitochondrial function as a prime factor in the aging process.
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PMID:Hyperoxia-induced clonogenic killing of HeLa cells associated with respiratory failure and selective inactivation of Krebs cycle enzymes. 223 21

Continuous exposure of Chinese hamster ovary (CHO) cells to an atmosphere of 98% O2, 2% CO2 (normobaric hyperoxia) leads within a period of several days to cytostasis and clonogenic cell death. Here we report respiratory failure as an important early symptom of oxygen intoxication in CHO cells, resulting in a more than 80% inhibition of oxygen consumption within 3 days of hyperoxic exposure. This inhibition appeared to be correlated with selective inactivation of three mitochondrial key enzymes, NADH dehydrogenase, succinate dehydrogenase, and alpha-ketoglutarate dehydrogenase. The latter enzyme controls the influx of glutamate into the Krebs cycle and is particularly critical for oxidative ATP generation in most cultured cells, which depends on exogenous glutamine rather than glucose as a carbon source. As expected, the inactivation of alpha-ketoglutarate dehydrogenase was correlated with a fall in cellular glutamine utilization, which became apparent from the first day of hyperoxic exposure. Thereafter, glucose utilization and lactate excretion started to increase, up to 3-fold, indicating a cellular response to respiratory failure aimed at increased ATP generation from glycolysis. However, in spite of this response, the cellular ATP level progressively decreased, up to 2.5-fold. Thus, killing of CHO cells by normobaric hyperoxia seems to be due to a severe disturbance of mitochondrial metabolism eventually leading to a depletion of cellular ATP pools.
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PMID:Respiratory failure and stimulation of glycolysis in Chinese hamster ovary cells exposed to normobaric hyperoxia. 235 58

CNS oxygen (O2) toxicity is complex, and the etiology of its most severe manifestation, O2 convulsions, is yet to be determined. A role for depletion of the brain GABA pool has been proposed, although recent data have implicated production of reactive O2 species, e.g. H2O2, in this process. We hypothesized that the production of H2O2 and NH3 produced by monoamine oxidase (MAO) would lead to depletion of GABA and production of nitric oxide (NO.) respectively, and thereby enhance CNS O2 toxicity. In this study, rats treated with an MAO inhibitor (pargyline) or a nitric oxide synthase inhibitor (LNNA) were protected against O2-induced convulsions. Selected cerebral amino acids including arginine were measured in control and O2 treated rats (6 ATA, 20 min) with or without drug pretreatment. After O2 exposure, the cerebral pools of glutamate, aspartate, and GABA decreased significantly while glutamine content increased relative to control (P < 0.05). After treatment with either enzyme inhibitor, glutamine, glutamate and aspartate concentrations were maintained near control levels. Remarkably, GABA depletion by O2 was not prevented despite protection from seizures by both pargyline and LNNA. The NO. precursor, arginine, was increased significantly in the brain by toxic O2 exposure, but both pargyline and LNNA inhibited this effect. Simultaneous norepinephrine measurements indicated that its storage substantially decreased during hyperoxia (P < 0.05), but this effect too was blocked by either pargyline or LNNA. These data indicate that protection against O2 by these inhibitors is not related to preservation of the GABA pool. More importantly, O2 dependent norepinephrine metabolism and NO. synthesis appear to be interactive during CNS O2 toxicity.
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PMID:Cerebral amino acid, norepinephrine and nitric oxide metabolism in CNS oxygen toxicity. 846 4

The supply of oxygen is a crucial parameter when cultivating animal cells in fixed-bed reactors because of the reaction-diffusion limitation within the porous carriers. To reduce limitation and increase productivity, the dissolved oxygen concentration was raised to above air saturation (hyperoxia) in long-term experiments using hybridoma cultures. This resulted in a threefold increase of the steady-state antibody production at high dilution rates compared to air saturated medium. A reaction-diffusion model was developed as a tool to describe the oxygen distribution in fixed-bed systems. The model corresponded well to the experimental data. It was also used to study the influence of several parameters on the performance of the fixed-bed system, such as the carrier size, the dissolved oxygen concentration, or the superficial flow velocity. By adapting the model it was shown that reaction-diffusion limitation is generally not a problem for other substrates such as glucose or glutamine.
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PMID:Experimental and theoretical considerations on oxygen supply for animal cell growth in fixed-bed reactors. 1044 23

Exposure to hyperoxia (500-600 torr) or low pH (4.5) for 72 h or NaHCO(3) infusion for 48 h were used to create chronic respiratory (RA) or metabolic acidosis (MA) or metabolic alkalosis in freshwater rainbow trout. During alkalosis, urine pH increased, and [titratable acidity (TA) - HCO(-)(3)] and net H(+) excretion became negative (net base excretion) with unchanged NH(+)(4) efflux. During RA, urine pH did not change, but net H(+) excretion increased as a result of a modest rise in NH(+)(4) and substantial elevation in [TA - HCO(-)(3)] efflux accompanied by a large increase in inorganic phosphate excretion. However, during MA, urine pH fell, and net H(+) excretion was 3.3-fold greater than during RA, reflecting a similar increase in [TA - HCO(-)(3)] and a smaller elevation in phosphate but a sevenfold greater increase in NH(+)(4) efflux. In urine samples of the same pH, [TA - HCO(-)(3)] was greater during RA (reflecting phosphate secretion), and [NH(+)(4)] was greater during MA (reflecting renal ammoniagenesis). Renal activities of potential ammoniagenic enzymes (phosphate-dependent glutaminase, glutamate dehydrogenase, alpha-ketoglutarate dehydrogenase, alanine aminotransferase, phosphoenolpyruvate carboxykinase) and plasma levels of cortisol, phosphate, ammonia, and most amino acids (including glutamine and alanine) increased during MA but not during RA, when only alanine aminotransferase increased. The differential responses to RA vs. MA parallel those in mammals; in fish they may be keyed to activation of phosphate secretion by RA and cortisol mobilization by MA.
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PMID:Renal responses of trout to chronic respiratory and metabolic acidoses and metabolic alkalosis. 1044 55

Glutamine is an important mitochondrial substrate implicated in the protection of cells from oxidant injury, but the mechanisms of its action are incompletely understood. Human pulmonary epithelial-like (A549) cells were exposed to 95% O2 for 4 days in the absence and presence of glutamine. Cell proliferation in normoxia was dependent on glutamine, and glutamine deprivation markedly accelerated cell death in hyperoxia. Glutamine significantly increased cellular ATP levels in normoxia and prevented the loss of ATP in hyperoxia seen in glutamine-deprived cells. Mitochondrial membrane potential as assessed by flow cytometry with chloromethyltetramethylrosamine was increased by glutamine in hyperoxia-exposed A549 cells, and a glutamine dose-dependent increase in mitochondrial membrane potential was detected. Glutamine-supplemented, hyperoxia-exposed cells had a higher O2 consumption rate and GSH content. Electron and fluorescence microscopy revealed that, in hyperoxia, glutamine protected cellular structures, especially mitochondria, from damage. In hyperoxia, activity of the tricarboxylic acid cycle enzyme alpha-ketoglutarate dehydrogenase was partially protected by its indirect substrate, glutamine, indicating a mechanism of mitochondrial protection.
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PMID:Glutamine protects mitochondrial structure and function in oxygen toxicity. 1123 20

High oxygen concentrations are used in the treatment of acute respiratory distress syndrome and hyaline membrane disease. Hyperoxia, however, can damage alveolar epithelial cells through the release of free oxygen radicals. Supplemental glutamine (Gln) has recently been shown to increase survival of A549 cells, a distal epithelial cell line, during hyperoxia (). We found that supplemental Gln (Gln+) is essential for cell growth in A549 cells. In room air, cells without supplemental Gln (Gln-) survived with BCL-2 levels similar to those of Gln+ cells, but cell growth was minimal. We also evaluated the role of glutamine synthetase (GS) in A549 cells during hyperoxia. L-methionine sulfoximine (MSO), an irreversible inhibitor of GS, was added to Gln+ and Gln- cells. In hyperoxia, Gln- cells had greater survival then Gln- cells treated with MSO. Supplemental Gln could rescue cells in hyperoxia from the effect of MSO, suggesting that GS, through the endogenous synthesis of Gln, could attenuate hyperoxic cell injury. In hyperoxia, cells treated with 10-mM concentrations of Gln had increased survival compared with cells receiving 2-mM concentrations. The higher concentration of Gln, however, did not decrease the percentage of cells undergoing necrosis.
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PMID:Inhibition of glutamine synthetase in a549 cells during hyperoxia. 1209 Dec 52

The use of high oxygen concentrations is frequently necessary in the treatment of acute respiratory distress syndrome (ARDS) and bronchopulmonary dysplasia (BPD). High oxygen concentrations, however, are detrimental to cell growth and cell survival. Glutamine (Gln) may be protective to cells during periods of stress and recently has been shown to increase survival in A549 cells exposed to lethal concentrations of oxygen (95% O2). We found that supplemental Gln enhances cell growth in A549 cells exposed to moderate concentrations of oxygen (60% O2). We therefore evaluated the effect of moderate hyperoxia on the cell cycle distribution of A549 cells. At 48 h there was no significant difference in the cell cycle distribution between 2 mM Gln cells in 60% O2 and 2 mM cells in room air. Furthermore, 2 mM Gln cells in 60% O2 had stable protein levels of cyclin B1 consistent with ongoing cell proliferation. In contrast, at 48 h, cells not supplemented with glutamine (Gln-) in 60% O2 had evidence of growth arrest by both flow cytometry (increased percentage of G1 cells) and by decreased protein levels of cyclin B1. G1 growth arrest in the Gln- cells exposed to 60% O2 was not, however, associated with induction of p21 protein. At 72 and 96 h, Gln- cells in 60% O2, began to demonstrate a partial loss of G1 checkpoint regulation and an increase in apoptosis, indicating an increased sensitivity to oxygen toxicity. Glutathione (GSH) concentrations were then measured. 2 mM Gln cells in 60% O2 were found to have higher concentrations of GSH compared to Gln- cells in 60% O2, suggesting that Gln confers protection to the cell during exposure to hyperoxia through up-regulation of GSH. When cells in 60% O2 were given higher concentrations of Gln (5 and 10 mM), cell growth at 96 h was increased compared to cells grown in 2 mM Gln (P<0.04). Clonal survival was also increased in cells exposed 60% O2 and supplemented with higher concentrations of Gln compared to Gln- cells in 60% O2. These studies suggest that supplemental glutamine may improve cell growth and cell viability and therefore may be beneficial to the lung during exposure to moderate concentrations of supplemental oxygen.
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PMID:The effect of glutamine on A549 cells exposed to moderate hyperoxia. 1499 Mar 41

Glutamine enhances the exercise-induced expansion of the tricarboxylic acid intermediate pool. The aim of the present study was to determine whether oral glutamine, alone or in combination with hyperoxia, influenced oxidative metabolism and cycle time-trial performance. Eight participants consumed either placebo or 0.125 g kg body mass(-1) of glutamine in 5 ml kg body mass(-1) placebo 1 h before exercise in normoxic (control and glutamine respectively) or hyperoxic (FiO(2) = 50%; hyperoxia and hyperoxia + glutamine respectively) conditions. Participants then cycled for 6 min at 70% maximal oxygen uptake (VO(2max)) immediately before completing a brief high-intensity time-trial (approximately 4 min) during which a pre-determined volume of work was completed as fast as possible. The increment in pulmonary oxygen uptake during the performance test (DeltaVO(2max), P = 0.02) and exercise performance (control: 243 s, s(x) = 7; glutamine: 242 s, s(x) = 3; hyperoxia: 231 s, s(x) = 3; hyperoxia + glutamine: 228 s, s(x) = 5; P < 0.01) were significantly improved in hyperoxic conditions. There was some evidence that glutamine ingestion increased DeltaVO(2max) in normoxia, but not hyperoxia (interaction drink/FiO(2), P = 0.04), but there was no main effect or impact on performance. Overall, the data show no effect of glutamine ingestion either alone or in combination with hyperoxia, and thus no limiting effect of the tricarboxylic acid intermediate pool size, on oxidative metabolism and performance during maximal exercise.
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PMID:No effect of glutamine supplementation and hyperoxia on oxidative metabolism and performance during high-intensity exercise. 1860 33


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