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

To determine whether glucose depletion is a principal determinant of hyperoxic cell death in vitro, human lung epithelial-like cells (A549) were exposed to hyperoxia (95% O2) in either 10, 30, or 50 ml of medium (Ham's F-12K). Glucose was depleted in the medium after 36, 60, or 96 h, respectively. Medium lactate dehydrogenase (LDH) activity increased only after glucose was depleted. To confirm that glucose depletion was critical to cell death, cells exposed to 95% O2 were supplemented with glucose at regular intervals to reestablish initial medium glucose concentrations. Other cells received no supplements. Without supplementation, glucose was depleted within 48 h, followed within 12 h by an almost complete loss of cell ATP and elevated medium LDH activity. Glucose-supplemented cells appeared normal microscopically and did not release LDH activity despite an extracellular pH of 6.5 due to fermentation. Additional experiments at sea-level pressure confirmed that glucose supplementation prevents extensive cell death in hyperoxia in cultured A549 cells.
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PMID:Glucose modulates cell death due to normobaric hyperoxia by maintaining cellular ATP. 945 14

We hypothesized that manganese superoxide dismutase (MnSOD), known to be induced in rat mesothelial cells by asbestos fibers, cytokines, and hyperoxia, may also be induced in asbestos-related pleural diseases such as mesothelioma. MnSOD was assessed in healthy human pleural mesothelium (n = 6), in biopsy samples of human pleural mesothelioma (n = 7), in transformed nonmalignant human mesothelial cells (Met5A), and in two human mesothelioma cell lines (M14K and M38K) established from the tumor tissue of mesothelioma patients. There was no MnSOD immunoreactivity in five of the six samples of healthy pleural mesothelium, whereas MnSOD immunoreactivity was high in the tumor cells in all the mesothelioma samples. Northern blotting, immunohistochemistry, Western blotting, and specific activity measurements showed lower MnSOD in the nonmalignant Met5A mesothelial cells than in the M14K and M38K mesothelioma cells. In additional experiments the mesothelial and mesothelioma cells were exposed to menadione, which generates superoxide intracellularly, and to epirubicin, a cytotoxic drug commonly used to treat mesothelioma. The M38K mesothelioma cells were most resistant to menadione and epirubicin when assessed by LDH release or by adenine nucleotide (ATP, ADP, and AMP) depletion. These same cells showed not only the highest MnSOD levels, but also the highest mRNA levels and activities of catalase, whereas glutathione peroxidase and glutathione reductase levels did not differ significantly. We conclude that MnSOD expression is low in healthy human pleural mesothelium and high in human malignant mesothelioma. The most resistant mesothelioma cells contained coordinated induction of MnSOD and catalase.
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PMID:Manganese superoxide dismutase in healthy human pleural mesothelium and in malignant pleural mesothelioma. 953 46

The brain is susceptible to oxidative stress. This is due to the high content of polyunsaturated fatty acids, high rate of oxygen consumption, regional high concentrations of iron, and relatively low antioxidant capacity. These factors may predispose the premature infant to brain damage. Brain damage may be due to: 1. Brief anoxia followed by hyperoxia (mimics parturition oxidative stress); or 2. Prolonged exposure to hyperoxia (mimics oxidative stress from postpartum maintenance in a hyperoxic environment). We have developed two animal models to examine these forms of oxidative stress on the brains of rats. In Model I rats were exposed to brief anoxic anoxia (100% N2) followed by hyperoxia (100% O2). Using T2-weighted Magnetic Resonance Imaging (MRI) brain intensity decreased following the treatment suggesting water loss or free radical production. In vivo 1H-NMR showed brain water content appeared to increase, however variability rendered this result insignificant. Electron spin resonance (ESR) spin trapping, using a-phenyl-N-tert-butylnitrone (PBN) produced a free radical signal from the anoxic-anoxia hyperoxia treated animals which suggests the decrease in MRI T2-weighted image signal intensity was due to free radicals. In Model II, we examined the effects of prolonged normobaric hyperoxia (85% O2) on blood-brain barrier (BBB) integrity and brain phosphorous metabolism. BBB permeability increased following 1 week of hyperoxia. In addition, measurement of high energy phosphates, using in vivo 31P-NMR, showed the PCr/ATP ratio significantly decreased, the ATP/Pi ratio increased and the (ATP+PCr)/Pi ratio increased. Because the BBB is sensitive to oxidative stress its loss of integrity may be due to free radicals. The level of oxidative stress may result in brain elevation of ATP as an adaptation mechanism. In conclusion, anoxic-anoxia and prolonged hyperoxia exposure produce MRI visible changes in the brain. These two mechanisms may be important in the etiology of brain damage observed in many premature infants.
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PMID:Effect of oxidative stress on brain damage detected by MRI and in vivo 31P-NMR. 960 4

Acute and chronic lung injury secondary to hyperoxia remains an important complication in critically ill patients, and, consequently, there is interest in developing strategies to protect the lung against hyperoxia. Heat shock proteins (HSPs) confer protection against a broad array of cytotoxic agents. In this study, we tested the hypothesis that increased expression of the 70-kDa HSP (HSP70) would protect cultured human respiratory epithelium against hyperoxia. Recombinant A549 cells were generated in which human HSP70 was increased by stable transfection with a plasmid containing human HSP70 cDNA under control of the cytomegalovirus promoter (A549-HSP70 cells). A549-HSP70 cells exposed to hyperoxia had greater acute survival rates and clonogenic capacity compared with wild-type A549 cells and with control cells stably transfected with the empty expression plasmid. Hyperoxia-mediated lipid peroxidation and ATP depletion were also attenuated in A549-HSP70 cells exposed to hyperoxia. Increased expression of HSP70 did not detectably alter mRNA levels of the intracellular antioxidants manganese superoxide dismutase, catalase, and glutathione peroxidase. Collectively, these data demonstrate a specific in vitro protective role for HSP70 against hyperoxia and suggest that potential mechanisms of protection involve attenuation of hyperoxia-mediated lipid peroxidation and ATP depletion.
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PMID:Increased expression of heat shock protein-70 protects A549 cells against hyperoxia. 975 17

This study was undertaken to examine the combined effect of nitric oxide (NO) and hyperoxia on lung edema and Na,K-ATPase expression. Newborn piglets were exposed to room air (FiO2 = 0.21), room air plus 50 ppm NO, hyperoxia (FiO2 >/= 0.96) or to hyperoxia plus 50 ppm NO for 4-5 days. Animals exposed to NO in room air experienced only a slight decrease in Na,K-ATPase alpha subunit protein level. Hyperoxia, in the absence of NO, induced both the mRNA and the protein level of Na,K-ATP-ase alpha subunit and significantly increased wet lung weight, extravascular lung water, and alveolar permeability. NO in hyperoxia decreased the hyperoxic-mediated induction of Na,K-ATPase alpha subunit mRNA and protein while wet lung weight, extravascular lung water, and alveolar permeability remained elevated. These results suggest that 50 ppm of inhaled NO may not improve hyperoxic-induced lung injury and may interfere with the expression of Na,K-ATPase which constitutes a part of the cellular defense mechanism against oxygen toxicity.
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PMID:Influence of inhaled nitric oxide and hyperoxia on Na,K-ATPase expression and lung edema in newborn piglets. 992 7

Cyclosporin A (CsA), an inhibitor of protein phosphatase 2B (calcineurin), has been shown to play a role in exocytosis and neutrophil mobility. Hyperoxia (>95% oxygen for 72 h) causes lung injury and reduces lung compliance. This model is indicative of deficiencies in surfactant and elicits a vigorous immune response leading to further damage. We examined the effects of CsA on surfactant-secreting lung alveolar type II cells. CsA enhances ATP-stimulated increases in whole cell capacitance in the presence of 2 mM extracellular Ca2+. This measurement corresponds with increases in exocytosis. Because of its effect on the immune system and exocytosis from type II cells, CsA was examined for its protective effects against hyperoxia-induced lung damage in mice. We found that CsA (50 mg. kg-1. day-1) attenuated hyperoxia-induced reductions in lung compliance when administered before or during 72 h of >95% oxygen (P < 0.05). CsA (10 mg. kg-1. day-1) also had a protective effect against hyperoxia-induced changes in neutrophil infiltration, capillary congestion, edema, and hyaline membrane formation. Wet lung weight-to-dry lung weight ratios did not show any significant changes after hyperoxia or hyperoxia plus CsA (P < 0. 05). CsA may be useful to treat patients undergoing prolonged high-oxygen therapy and possibly other lung injuries.
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PMID:Cyclosporin A protects lung function from hyperoxic damage. 1033 35

We evaluated the effects of intraalveolar oxygen concentration on alveolar fluid absorption and metabolism in isolated rat lungs. Alveolar fluid absorption was determined by measuring increase in albumin concentration in the instillate solution during 2 h of incubation. Oxidative phosphorylation was assessed by gas analysis of the solution. Glycolysis was assessed by determining glucose escape and lactate release in the solution. We found that alveolar fluid absorption did not change under hyperoxic and hypoxic experimental environments (range 100-10% oxygen). Glycolysis was reduced under hyperoxia and stimulated under hypoxia, however, lung ATP content did not change. When oxidative phosphorylation was inhibited by NaCN, both alveolar fluid absorption and lung ATP content were reduced. Our data indicate that isolated rat lungs maintain optimal energy production for alveolar fluid absorption by stimulating glycolysis, even though glycolysis alone is not enough. We conclude that alveolar fluid absorption determined in isolated rat lungs is not influenced by intraalveolar oxygen concentration in the range above 10% oxygen.
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PMID:Effects of intraalveolar oxygen concentration on alveolar fluid absorption and metabolism in isolated rat lungs. 1042 62

The hyperoxia-improved tolerance to maximal aerobic performance was studied in relation to exercising muscle metabolic state. Five students were submitted to four different tests on a cycle ergometer, each being conducted under normoxia and hyperoxia (60% FiO2) on separate days: Test 1, a progressive exercise until exhaustion to determine the maximal work load (Wmax) which was unchanged by hyperoxia; Test 2, an exercise at Wmax (287 +/- 12 W) until exhaustion to determine the performance time (texh) which was elevated by 38% under hyperoxia but exhaustion occurred at the same arterial proton and lactate concentrations; Test 3 (S-Exercise test) consisted of cycling at Wmax for 90% normoxic-texh (4.8 +/- 0.5 min under both O2 conditions) then followed by a 10-s sprint bout during which the total work output (Wtot) was determined; Wtot was elevated by 15% when exercising under hyperoxia; Test 4 (M-Exercise test) consisted also of cycling at Wmax for 4.8 +/- 0.5 min with blood and muscle samples taken at rest and at the end of the exercise to compare the level of different metabolites. During hyperoxic M-Exercise test, glycogen was twice more depleted whereas glucose-6-phosphate and lactate were less accumulated when compared with normoxia. No significant differences were observed for pyruvate, phosphocreatine and muscle/blood lactate ratio between the two conditions. Conversely to normoxia, levels of ATP, ADP and total NADH were maintained at their resting level under 60% FiO2. These data lead us to suppose a higher oxidation rate for pyruvate and NADH in mitochondria, thereby lowering the metabolic acidosis and allowing a better functioning of the glycolytic and contractile processes to delay the time to exhaustion.
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PMID:Effect of hyperoxia on aerobic and anaerobic performances and muscle metabolism during maximal cycling exercise. 1071 78

At term of pregnancy, oxygen consumption by the human or ovine placenta accounts for 40 per cent of total oxygen uptake by the gravid uterus. In the sheep, most oxygen is used for oxidative phosphorylation of glucose; the remainder is probably utilized for non-mitochondrial processes. The ATP yield is expended mainly in protein synthesis and cation transport. The fractional protein synthesis rate of ovine placenta is 60 per cent per day. Applying these data to man, protein synthesis is estimated to account for about 30 per cent of placental oxygen uptake. Probably this reflects the high rates of synthesis of peptide and steroid hormones. The Na+ gradient is the basis for secondary active transport of amino acids and other substances, and the Na(+)-K(+)-pump probably accounts for 20-30 per cent of oxygen uptake, with a smaller contribution from Ca(2+)-ATPase. Placental oxygen uptake remains constant during acute reductions in uterine oxygen supply and is maintained at the expense of the fetus. In the longer term, in experimental models of fetal growth restriction, placental oxygen consumption is reduced to a greater extent than fetal oxygen consumption. Placental oxygen consumption is greatly reduced under in vitro experimental conditions, due largely to an inadequate oxygen supply. This results in reduced protein synthesis and possibly inhibition of Na(+)-K(+)-ATPase. However, if the placenta is subjected to hyperoxia, by raising the PO2 of the medium, there is an increase in anaerobic glycolysis and structural damage may ensue. Premature exposure of trophoblast to high oxygen tensions in vivo may result in reduced villous branching, but this is likely to be a cause, rather than a consequence, of reduced fetal growth and oxygen consumption.
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PMID:Placental oxygen consumption. Part I: in vivo studies--a review. 1083 Nov 19

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


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