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

Toxicity to the central nervous system (CNS) by hyperbaric oxygen (HBO) presumably relates to increased production of reactive oxygen species. The sites of generation of reactive oxygen species during HBO, however, have not been fully characterized in the brain. We investigated the relationship between regional generation of hydrogen peroxide (H2O2) in the brain in the presence of an irreversible inhibitor of catalase, aminotriazole (ATZ), and protection from CNS O2 toxicity by a monoamine oxidase (MAO) inhibitor, pargyline. At 6 ATA of oxygen, pargyline significantly protected rats from CNS O2 toxicity whereas ATZ enhanced O2 toxicity. In animals pretreated with ATZ, HBO inactivated 21-40% more catalase than air exposure in the six brain regions studied. Because ATZ-mediated inactivation of catalase was H2O2 dependent, the decrease in catalase activity during hyperoxia was proportional to the intracellular production of H2O2. Pargyline, administered 30 min before HBO, inhibited MAO by greater than 90%, prevented ATZ inhibition of catalase activity during HBO, and reversed the augmentation of CNS O2 toxicity by ATZ. These findings indicate that H2O2 generated by MAO during hyperoxia is important to the pathogenesis of CNS O2 toxicity in rats.
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PMID:Prevention of H2O2 generation by monoamine oxidase protects against CNS O2 toxicity. 175 1

The ability of niacin to relieve the growth-inhibiting effect of hyperoxia on Escherichia coli can be attributed to the dioxygen sensitivity of quinolinate synthetase. The activity of this enzyme within E. coli was diminished by exposure of the cells to 4.2 atm O2, while the activity in extracts was rapidly decreased by 0.2 atm O2. Neither catalase nor superoxide dismutase afforded detectable protection against the inactivating effect of O2, indicating that H2O2 and O2- were not significant intermediates in this process. Nevertheless, H2O2 at 1.0 mM did inactivate quinolinate synthetase, even under anaerobic conditions and in the absence of catalatic activity which might have generated O2. Addition of paraquat to aerobic cultures of E. coli caused an inactivation of quinolinate synthetase, which may be explained in terms of an increase in the production of H2O2. The O2-dependent inactivation of quinolinate synthetase in extracts was gradually reversed during anaerobic incubation and this reactivation was blocked by alpha, alpha'-dipyridyl or by 1,10-phenanthroline. The sequence of the quinolinate synthetase "A" protein contains a--cys-w-x-cys-y-z-cys--sequence, which is characteristic of (Fe-S)4-containing proteins. This sequence, together with the effect of the Fe(II)-chelating agents, suggests that the O2-sensitive site of quinolinate synthetase is an iron-sulfur cluster which is essential for the dehydration reaction catalyzed by the A protein.
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PMID:Quinolinate synthetase: the oxygen-sensitive site of de novo NAD(P)+ biosynthesis. 184 9

Extracellular H2O2 release and intracellular H2O2 production were determined in rat lung alveolar macrophages, rat alveolar type II cells, and cultured bovine aortic endothelial cells. Isolated macrophages (5 h ex vivo) released 3.1 +/- 0.09 nmol H2O2.min-1.mg cell protein-1, freshly isolated (5 h ex vivo) type II cells released 0.7 +/- 0.07 nmol H2O2.min-1.mg protein-1, and cultured endothelial cells released 0.06 +/- 0.005 nmol H2O2.min-1.mg protein-1. The rate of extracellular H2O2 release decreased rapidly over time in both fresh macrophages and freshly isolated type II cells. When the measurements were repeated at different times ex vivo, the decrease was greater than 20%/h, and H2O2 release was almost undetectable 12 h ex vivo. The decrease occurred while lactate dehydrogenase release, catalase activity, and intracellular H2O2 production remained unchanged. Catalase activity was 59.3 +/- 4.9 nmol O2 produced.min-1.mg protein-1 in type II cells, 13.2 +/- 1.8 in macrophages, and 11.4 +/- 2.7 in endothelial cells. Aminotriazole is a compound that inhibits catalase in the presence of H2O2 at a rate that is proportional to the rate of intracellular H2O2 production in or near peroxisomes. Incubation of the cells with aminotriazole led to a rapid inhibition of catalase. In 15 min the reduction of catalase activity was 69% in type II cells, 53% in macrophages, and 37% in endothelial cells. When freshly isolated type II cells were exposed to hyperoxia (95% O2) for 30 min, no changes in the rate of either intracellular H2O2 production or extracellular H2O2 release were seen.
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PMID:Hydrogen peroxide production by alveolar type II cells, alveolar macrophages, and endothelial cells. 187 19

Our study was designed to assess the role of selenium (Se) in development of neonatal lungs under conditions of normoxia and hyperoxia. Thirty-six female Sprague Dawley rats were bred and fed a Se-deficient (0.03 ppm Se) or a Se-adequate (0.5 ppm Se) diet during pregnancy and lactation. At d 2 postpartum, 24 litters were randomly assigned to either high oxygen (greater than 95%) or air and were cross-fostered for 4 d. Lung weight was significantly enhanced in Se-adequate pups and was not related to high oxygen or air exposure of either the pups or dams. Two types of histologic lesions were observed in the lungs of the pups: septal attenuation and interstitial inflammation. When reared in oxygen, all (17 of 17) Se-deficient pups had lesions. In contrast, only 60% (9 of 15) of Se-adequate pups were affected (p less than 0.01). Lung lesions also were more severe in Se-deficient pups. Se-deficient pups also displayed a significant degree of septal attenuation when reared in air. Se-dependent glutathione peroxidase activity in the pup lung was significantly elevated in response to hyperoxia and was unrelated to Se nutriture. No differences in activities of lung superoxide dismutase, catalase, and glutathione s-transferase were noted between Se-deficient and Se-adequate pups reared in air or high oxygen environments. These data indicate that Se has an important role in the development of neonatal lungs, a role that is even more pronounced during conditions of hyperoxia. The protective role of Se in developing lung tissue cannot be completely explained by enhanced glutathione peroxidase activity.
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PMID:The role of selenium nutrition in the development of neonatal rat lung. 189 47

Exposure of cultured pulmonary artery endothelial cells to 95% O2 resulted in the following sequence of events: decrease in [3H]thymidine incorporation after 24 h; increase of intracellular glutathione (GSH) and loss of cellular protein after 48 h; increase of spontaneous and decrease of provoked prostacyclin formation as well as increased release of cellular LDH after 72 h. This oxygen toxicity model was used to study the following 2 questions. (1) What is the relative importance of the GSH redox cycle compared to catalase as antioxidative defense against hyperoxia? Endothelial cells were grown in selenium-depleted medium to inhibit glutathione peroxidase activity. Endothelial GSH biosynthesis was inhibited by buthionine sulfoximine. Catalase activity was reduced by aminotriazole. Endothelial cells with an impaired GSH redox cycle were easily killed by hyperoxia within 24 h, while inhibition of catalase did not enhance the susceptibility of endothelial cells to hyperoxia. (2) Can endothelial GSH content be increased by exogenous sulfhydryl reagents and does this result in an increase of endothelial cells' resistance to hyperoxia? Exogenous GSH, N-acetylcysteine, cysteine, and L-2-oxothiazolidine-4-carboxylate (L-2-oxo) increased intracellular GSH. All sulfhydryl reagents (with the exception of L-2-oxo) protected endothelial cells from hyperoxia. Concentrations of exogenous GSH and N-acetylcysteine that did not increase intracellular GSH reduced hyperoxia-induced endothelial cell injury. Thus the capacity of the GSH redox cycle rather than intracellular GSH levels or catalase determines endothelial cells' resistance to hyperoxia.
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PMID:Glutathione redox cycle is an important defense system of endothelial cells against chronic hyperoxia. 192 73

The effects of hyperoxia and the response of oxygen free radical defense enzymes in the lung and extracellular environment of the lung were measured in Zn-deficient rats. Although lung was the target organ as indicated by the increased lung:body weight ratio in all hyperoxia-exposed rats regardless of dietary regimen, 85% oxygen exposure seemed to impose a stress on the whole animal as indicated by decreased feed intake and body weight in ad libitum-fed rats. Hyperoxia exposure superimposed on Zn deficiency did not further reduce the feed intake or body weight of Zn-deficient rats. After 7 d of hyperoxia exposure, the Zn-repleted and ad libitum-fed groups consistently had increased activity of lung CuZn-superoxide dismutase (CuZnSOD), glutathione peroxidase and catalase; but changes in CuZnSOD activity were not related to lung Cu or Zn concentrations. Although Zn-deficient and pair-fed rats were unable to increase CuZnSOD activity, they had an increased lung Zn concentration compared with their air-exposed counterparts. Hyperoxia exposure also caused an increase in ceruloplasmin activity of pair-fed and ad libitum-fed control rats. We concluded that dietary Zn repletion started at the beginning of 85% oxygen exposure was effective for increasing the activity of the lung oxygen free radical defense enzymes, thus preventing hyperoxia-induced lung damage in Zn-deficient rats.
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PMID:Effect of hyperoxia on oxygen free radical defense enzymes in the lung of zinc-deficient rats. 200 99

Although the prematurely born are known to have decreased baseline levels of protective antioxidant enzymes (Frank L, Sosenko IRS: J Pediatr 110:9 and 106, 1987), the ability to augment the baseline values during high O2 exposure is the key factor determining O2 tolerance versus O2 susceptibility. We have compared the pulmonary antioxidant enzyme responses of prematurely delivered rabbits (gestational d 29 of 32) and full-term rabbits to 48-72 h of hyperoxic exposure. We found that although full-term newborns exposed to greater than 90% O2 consistently showed elevated superoxide dismutase, catalase, glutathione peroxidase, and glucose-6-phosphate dehydrogenase activities, the premature animals repeatedly failed to respond to hyperoxia with increased antioxidant enzyme activity levels. Consistent with the comparative antioxidant enzyme responses were the evidences of O2 toxicity in the two age groups. The prematurely born rabbits had significantly increased lung lavage protein content, lung conjugated diene levels, and more severe light microscopic lung pathology compared with the full-term animals during equal O2 exposure time. This first reported comparison of prematurely born versus full-term animal responses to hyperoxia might help to explain the clinical observation that the very prematurely born infant is excessively prone to the development of O2-induced lung injury and the progressive development of bronchopulmonary dysplasia.
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PMID:Failure of premature rabbits to increase antioxidant enzymes during hyperoxic exposure: increased susceptibility to pulmonary oxygen toxicity compared with term rabbits. 203 78

It is now becoming increasingly clear that free radicals contribute to brain damage in several conditions, such as hyperoxia and trauma. It has been more difficult to prove that free radical production mediates ischemic brain damage, but it has often been suggested that it may be a major contributor to reperfusion damage, observed following transient ischemia. Recent results demonstrate that cerebral ischemia of long duration, particularly when followed by reperfusion, leads to enhanced production of partially reduced oxygen species, notably hydrogen peroxide (H2O2). It has also been suggested that postischemic hyperoxia, e.g. an increased oxygen tension during the recirculation period, adversely affects recovery following transient ischemia. Other data support the notion that brain damage caused by permanent ischemia (stroke) is significantly influenced by production of free radicals. The present study, however, fails to show that recirculation following brief periods of ischemia (15 min) leads to an enhanced H2O2 production, and that hyperoxia aggravates the ischemic damage. This study was undertaken to reveal whether variations in oxygen supply in the postischemic period following forebrain ischemia in rats affect free radical production and the brain damage incurred. To that end, rats ventilated on N2O/O2 (70:30) were subjected to 15 min of transient ischemia. Normoxic animals were ventilated with the N2O/O2 mixture, hyperoxic animals with 100% O2, and hypoxic ones with about 10% O2 (balance either N2O/N2 or N2) during the recirculation. At the end of this period, the animals were decapitated for assessment of H2O2 production with the aminotriazole/catalase method. This method is based on the notion that aminotriazole interacts with H2O2 to inactivate catalase; thus, the rate of inactivation of catalase in aminotriazole treated animals reflects H2O2 production. In a parallel series, animals ventilated with one of the three gas mixtures in the early recirculation period, respectively, were allowed to recover for 7 days, with subsequent perfusion-fixation of brain tissues and light microscopical evaluation of the brain damage. Animals given aminotriazole, whether rendered ischemic or not, showed a reduced tissue catalase activity, reflecting H2O2 production in the brain. Hyperoxic animals failed to show increased tissue H2O2 production, while hypoxic ones showed a tendency towards decreased production. However, all three groups (hypo, normo- and hyperoxic) had similar density and distribution of neuronal damage. These results suggest that although postischemic oxygen tensions may determine the rates of H2O2 production, variations in oxygen tensions do not influence the final brain damage incurred.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Free radical production and ischemic brain damage: influence of postischemic oxygen tension. 205 15

Metabolites of arachidonic acid (AA) released into bronchoalveolar lavage fluid of animals exposed to hyperoxia have previously been implicated as mediators of pulmonary oxygen toxicity. The alveolar macrophage (AM) represents an important potential source of these eicosanoids. We have therefore investigated the effects of in vitro hyperoxia (95% O2/5% CO2) versus normoxia (95% air/5% CO2) on the metabolism of AA in the AM of the rat. Exposure to 95% O2 for up to 72 h did not impair the viability or affect the protein content of cultured AMs. Hyperoxia for 24 to 72 h increased the accumulation of free AA liberated from endogenous stores in cultures of resting AMs. Despite this increase in free AA, no changes in synthesis of thromboxane B2, prostaglandin (PG) E2, PGF2 alpha, leukotriene (LT) B4, or LTC4 were observed in resting AMs exposed to hyperoxia for up to 72 h. This was not due to degradation of eicosanoids in hyperoxia. However, formation of cyclooxygenase metabolites from exogenously supplied AA was reduced in hyperoxia-incubated AMs, suggesting that hyperoxia inhibited the cyclooxygenase enzyme. In AMs stimulated with calcium ionophore A23187, both AA release and synthesis of cyclooxygenase and lipoxygenase eicosanoids were augmented after incubation in hyperoxia for 24 to 72 h. The increase in A23187-stimulated LTB4 synthesis caused by hyperoxia was inhibited by the antioxidants catalase, superoxide dismutase, and the intracellular cysteine loading agent L-2-oxothiazolidine-4-carboxylic acid, suggesting that the augmentation by hyperoxia of A23187-induced AA metabolism was mediated by reactive oxygen metabolites. Thus, hyperoxia has complex effects on AA metabolism in the AM, which include the ability to augment the release of AA and formation of bioactive eicosanoids. These findings support a possible role for eicosanoid synthesis by the AM in the pathogenesis of oxygen toxicity of the lung.
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PMID:Complex effects of in vitro hyperoxia on alveolar macrophage arachidonic acid metabolism. 215 14

The Fischer rat is known for its susceptibility to develop liver necrosis when challenged with paraquat (Smith et al., J. Pharmacol. Exp. Ther. 235: 172-177, 1985). We postulated that other organs, specifically the lung, may also be more susceptible to injury and examined whether lungs from Fischer (F) rats were injured more easily when challenged with active oxygen species than Sprague-Dawley (SD) rat lungs. We aimed to investigate whether increased susceptibility to oxidant injury was related to differences in lung antioxidant defenses. Perfused lungs from both rat strains were challenged by addition of H2O2 to the perfusate or by short-term hyperoxic ventilation. To assess nonoxidant modes of lung injury, we examined lung responses after exposure to protamine sulfate or neutrophil elastase. Intravascular H2O2 or 3 h in vitro hyperoxia caused lung edema in F but not SD rats, and elastase injured F rat lungs more than the lungs from SD rats. Protamine, however, injured the lungs from both strains to a similar degree. Catalase, but not superoxide dismutase or allopurinol, protected F rat lungs against edema, resulting from 3 h in vitro hyperoxia. The lung homogenate levels for reduced glutathione or conjugated dienes and the activities of lung tissue catalase, glutathione peroxidase, and cytochrome P-450 were not different between the two strains. Lung tissue ATP levels, however, were lower in F than in SD rats. Although the F rat strain appears to have an altered oxidant-antioxidant defense balance, the exact cause of the greater susceptibility to oxidant stress of the F rat strain remains elusive.
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PMID:Lung injury in Fischer but not Sprague-Dawley rats after short-term hyperoxia. 226 Jun 76


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