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

Hyperoxia and hyperbaric hyperoxia increased the rate of cerebral hydrogen peroxide (H2O2) production in unanesthetized rats in vivo, as measured by the H2O2-mediated inactivation of endogenous catalase activity following injection of 3-amino-1,2,4-triazole. Brain catalase activity in rats breathing air (0.2 ATA O2) decreased to 75, 61, and 40% of controls due to endogenous H2O2 production at 30, 60, and 120 min, respectively, after intraperitoneal injection of 3-amino-1,2,4-triazole. The rate of catalase inactivation increased linearly in rats exposed to 0.6 ATA O2 (3 ATA air), 1.0 ATA O2 (normobaric 100% O2) and 3.0 ATA O2 (3 ATA 100% O2) compared with 0.2 ATA O2 (room air). Catalase inactivation was prevented by pretreatment of rats with ethanol (4 g/kg), a competitive substrate for the reactive catalase-H2O2 intermediate, compound I. This confirmed that catalase inactivation by 3-amino-1,2,4-triazole was due to formation of the catalase-H2O2 intermediate, compound I. The linear rate of catalase inactivation allows estimates of the average steady-state H2O2 concentration within brain peroxisomes to be calculated from the formula: [H2O2] = 6.6 pM + 5.6 ATA-1 X pM X [O2], where [O2] is the concentration of oxygen in ATA that the rats are breathing. Thus the H2O2 concentration in brains of rats exposed to room air is calculated to be about 7.7 pM, rises 60% when O2 tension is increased to 100% O2, and increases 300% at 3 ATA 100% O2, where symptoms of central nervous system toxicity first become apparent. These studies support the concept that H2O2 is an important mediator of O2-induced injury to the central nervous system.
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PMID:Hyperoxia increases H2O2 production by brain in vivo. 362 37

Oxidants are generated in vivo by multiple mechanisms, including stimulation of leukocytes, hyperoxia, metabolism of arachidonic acid, and the activation of various oxidases. When the biochemical defences to the oxidants are inadequate, injury of tissues results. This injury was observed in rabbits and rhesus monkeys when pulmonary inflammation was induced with phorbol esters or formylated peptide given intrabronchially. We have recently investigated metabolic changes in various cells exposed to oxidants that are generated from stimulated leukocytes, including H2O2, O2, and HOCl. The target cells used were P388D1 murine macrophage-like tumour cells, human peripheral lymphocytes, GM 1380 human fibroblasts and rabbit alveolar macrophages. The oxidants used were H2O2 and PMA stimulated PMNs or neutroplasts. Lysis could only be prevented when catalase was added within the first 30-40 min of H2O2 exposure indicating that early metabolic changes determined the fate of the cell. Within seconds after the addition of H2O2 to P388D1 cells activation of the hexose monophosphate shunt (HMPS) was observed indicative of increased glutathione cycle activity. At the same time DNA strand breaks (determined by an alkaline unwinding technique) were detected. They resulted in the activation of the DNA repair enzyme poly-ADP-ribose polymerase (pADP-RP) within minutes after the addition of H2O2. At the same time ATP and NAD (the substrate of pADP-RP) concentrations dropped and nicotinamide accumulated extracellularly. 10-15 min after oxidant exposure free intracellular Ca++ concentrations determined by Quin 2 fluorescence started to increase due to release from intracellular stores.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxidant and protease injury of the lung. 369 17

Increased cellular generation of partially reduced species of oxygen mediates the toxicity of hyperoxia to cultured endothelial cells and rats exposed to 95-100% oxygen. Liposomal entrapment and intracellular delivery of superoxide dismutase (SOD) to cultured porcine aortic endothelial cells increased the specific activity of cellular SOD up to 15-fold. The liposome-mediated augmentation of SOD activity persisted in cell monolayers and rendered these cells resistant to oxygen-induced injury in a cell SOD activity-dependent manner. Addition of free SOD to culture medium had no effect on cell SOD activity or resistance to oxygen toxicity. SOD and catalase-containing liposomes injected i.v. into rats increased lung-associated enzyme specific activities two- to fourfold. Liposome entrapment of both SOD and catalase significantly increased the circulating half-lives of these enzymes and was critical for prevention of in vivo oxygen toxicity. Free SOD and catalase injected i.v. in the absence or presence of control liposomes did not increase corresponding lung enzyme activities or survival time in 100% oxygen. These studies show that O2- and H2O2 are important mediators of oxygen toxicity and that intracellular delivery of oxygen protective enzymes can reduce tissue injury owing to overproduction of partially reduced oxygen species.
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PMID:Modulation of oxidant lung injury by using liposome-entrapped superoxide dismutase and catalase. 400 80

Toxic, partially reduced metabolites of oxygen (toxic oxygen radicals) are increasingly implicated in acute leukocyte-mediated tissue injury. To further probe the roles of oxygen radicals in acute lung edema, I studied the effects of a recently described and very potent oxygen radical scavenger, dimethylthiourea (DMTU) (Fox, R. B., R. N. Harada, R. M. Tate, and J. E. Repine, 1983, J. Appl. Physiol., 55:1456-1459) on polymorphonuclear leukocyte (PMN) oxidant function and on two types of lung injury mediated by oxygen radicals and PMN. DMTU (10 mM) blocked 79% of hydroxyl radical (OH) production by PMN in vitro without interfering with other PMN functions, such as O-2 production, myeloperoxidase activity, chemotaxis, degranulation, or aggregation. When isolated rat lung preparations were perfused with PMN activated to produce OH, lung weights were increased from 2.3 +/- 0.2 to 11.2 +/- 0.8 g. DMTU (10 mM) prevented 70% of these increases (lung weights, 5.0 +/- 1.1 g, P less than 0.005). Finally, when intact rats were exposed to 100% O2 for 66 h, lung weight:body weight ratios were increased from 5.78 +/- 0.33 to 8.87 +/- 0.16 g. DMTU (500 mg/kg) prevented 83% of this hyperoxia-induced lung edema in vivo (lung:body weight ratios, 6.05 +/- 0.21, P less than 0.001). Pharmacokinetic studies showed that DMTU diffused effectively into lung interstitial fluids and had a relatively long half-life (25-35 h) in the circulation. Because a variety of oxygen radicals, such as superoxide (O-2), hydrogen peroxide (H2O2), or OH are produced by PMN, there is usually some uncertainty about which one is responsible for injury. However, in these studies, DMTU did not scavenge O-2 and scavenged H2O2 only very slowly while scavenging OH very effectively. Therefore, DMTU may be useful in the investigation of the roles of oxygen radicals, especially OH, in acute granulocyte-mediated tissue injury.
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PMID:Prevention of granulocyte-mediated oxidant lung injury in rats by a hydroxyl radical scavenger, dimethylthiourea. 609 May 4

The oxidant damage of lung tissue during in vivo hyperoxic exposure appears to be amplified by neutrophils that release toxic amounts of oxygen metabolites. In our studies cloned lung epithelial cells (L2 cells), lung fibroblasts, and pulmonary artery endothelial cells were cultured under either ambient (Po(2) approximately 140 torr) or hyperoxic (Po(2) approximately 630 torr) conditions for 48 h (24 h for endothelial cells). After cultivation, phorbol myristate acetate- or opsonized zymosan-stimulated neutrophils were added to the cultivated monolayers for 4 h, and lung cell damage was quantitated using (51)Cr release as an index. The data show that stimulated neutrophils are able to injure the three lung cell lines tested, with endothelial cells being highly susceptible to this injury and L2 cells being slightly more susceptible than lung fibroblasts. The studies also demonstrate that all three lung cell lines exposed to sustained hyperoxia are more susceptible to neutrophil-mediated cytotoxicity than their time-matched air controls. Hydrogen peroxide was the main toxic oxygen metabolite because catalase (2,500 U/ml) completely protected the target cells. Equivalent quantities of hydrogen peroxide generated by glucose oxidase instead of by neutrophils gave a similar degree of target cell injury. Superoxide dismutase at high concentrations (250 mug/ml) provided some protection. Other systems that detoxify oxygen metabolites were without protective effect. These findings indicate that the increase in susceptibility of lung cells to neutrophil-mediated oxidant damage is a toxic effect of hyperoxia on lung cells. This specific manifestation of oxygen damage provides insight into the integration between primary mechanisms (oxygen exposure) and secondary mechanisms (release of oxygen metabolites by neutrophils) with respect to the cellular basis for pulmonary oxygen toxicity.
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PMID:Lung cell oxidant injury. Enhancement of polymorphonuclear leukocyte-mediated cytotoxicity in lung cells exposed to sustained in vitro hyperoxia. 628

Lung macrophages (LM) play a crucial role in pulmonary bacterial defense. High inspired oxygen concentrations are used in a variety of diseases and "oxygen toxicity" could impair antibacterial function. We therefore examined the effect of sustained in vitro hyperoxia on LM bactericidal function, and on generation of two bactericidal oxygen metabolites. The LM were cultivated under aerobic (PO2 approximately 140 mmHg) or hyperoxic (PO2 approximately 630 mmHg) conditions for 48 h, and then incubated with Staphylococcus aureus labeled with 3H thymidine for 30 min. Incubated monolayers were processed for measurement of total bacterial uptake and for number of viable intracellular bacteria. Superoxide anion (O2-) and hydrogen peroxide (H2O2) generation was determined in similarly cultivated cells stimulated with opsonized zymosan. The results indicate that the bacterial killing capacity of oxygen-cultivated LM is significantly decreased (p less than 0.001). In addition, a significant (p less than 0.001) decrease in generation of O2- and H2O2 was noted after exposure to high oxygen tensions. The data suggest that decreased bactericidal function after sustained hyperoxia may be due to an impairment of a specific bactericidal mechanism, i.e., an impaired "respiratory burst."
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PMID:Decreased bactericidal function and impaired respiratory burst in lung macrophages after sustained in vitro hyperoxia. 631 Oct 64

Damage to alveolar macrophages (AM) from hyperoxia (95% O2) is associated with release of factors that recruit and activate neutrophils, but the mechanisms underlying injury to AM from hyperoxia are unknown. We hypothesized that damage to AM from hyperoxia involves generation of highly reactive toxic oxygen derivatives, and we tested this premise by exposing cultured rabbit AM to hyperoxia in the presence of scavengers that inactivate various reactive oxygen species. We found that either dimethyl thiourea, a scavenger of hydroxyl radical, or catalase, a scavenger of H2O2, protected cultured rabbit AM against hyperoxic damage, which suggests that H2O2 or an H2O2-derived product, such as hydroxyl radical, contribute to damage to AM from hyperoxia.
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PMID:Oxygen radical scavengers protect alveolar macrophages from hyperoxic injury in vitro. 641 52

Correlation between a pro-oxidant activity of blood, estimated by means of chemoluminescence in the system H2O2-luminol-blood plasma, and individual sensitivity of rabbits to the effect of oxygen was studied. Alterations in the blood pro-oxidant activity, as shown by treatment of the blood sample with 0.7 MPa of oxygen in vitro, correlated distinctly with the period of convulsions as well as with viability of animals during acute hyperoxia.
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PMID:[Biochemical estimation of individual sensitivity to oxygen intoxication in rabbits]. 650 86

Hyperoxia induced cellular damage was used as an experimental model system for examining the ameliorative role of antioxidants. Multiplication of HEp-2 cells in monolayer culture was inhibited after exposure to 100% O2 either hyperbarically at 3 atm absolute (atma) or normobarically at 1 atma for periods from 15 s to 4 h. The inhibition was characterized by a slower rate of replication for a period from 1 to 3 d after exposure than in unexposed cultures, and then massive cellular death. Less killing followed exposure to normobaric O2 than to hyperbaric O2, and the shorter the period of exposure to hyperoxia the less killing. Addition of 100 micrograms/ml of sodium L-ascorbate to unexposed cultures enhanced growth (cell number at 6 d) almost twofold. When added ascorbate was present only during hyperoxic exposure (but not afterward), subsequent growth in air was enhanced 1.6-fold. However, when cells were exposed without added ascorbate, there was from 2 to 12-fold greater growth in air in the presence of the added ascorbate (as compared to exposed controls). This greater growth was always only a partial reversal of the lethal effect resulting from hyperoxia. Addition of 25 micrograms/ml catalase did not affect control or exposed cultures. Addition of ascorbate plus catalase was not as effective as ascorbate alone in promoting growth; the catalase moiety antagonized some of the growth enhancing influence of ascorbate. This suggests that extracellular H2O2 was not a factor in the lethal effect resulting from hyperoxia.
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PMID:Partial reversal by sodium ascorbate of hyperoxia-induced damage to HEp-2 cell cultures. 685 35

Adult rats preexposed to 10% O2 for 3 days had marked tolerance to hyperoxia-induced lung damage and lethality. The survival of preexposed vs. nonpreexposed rats at 72 h of hyperoxic exposure was 62/62 vs. 7/47 (15%), P less than 0.0001; and after 7 days in 96-98% O2, the comparative survival was 31/33 (94%) vs. 1/20 (5%), P less than 0.0005. Hypoxic exposure produced significant elevations in rat lung superoxide dismutase, catalase, glutathione peroxidase, and glucose-6-phosphate dehydrogenase activities. In contrast, in adult mice and hamsters, no increased lung antioxidant enzyme levels were produced by preexposure to hypoxia and no significant tolerance to high O2 was realized. (Lethal time50 values for hypoxia-preexposed and nonpreexposed mice, 5.2 and 4.4 days, respectively; and for hamsters, 6.4 and 6.1 days, respectively.) Thus the protective effect of hypoxic preexposure is correlated with adaptive changes in lung antioxidant enzyme activity. Evidence in the literature suggests that superoxide anion (O-2) and H2O2 production may increase under hypoxic conditions. Increased cellular concentrations of their normal substrates could stimulate antioxidant enzyme rises during the preexposure period in hypoxia.
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PMID:Protection from O2 toxicity by preexposure to hypoxia: lung antioxidant enzyme role. 711 67


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