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

To study the cellular defense mechanism against oxygen toxicity, an oxygen-tolerant cell line from Chinese hamster ovary (CHO) was obtained by multistep adaptation to increased O2 levels. The hyperoxia-adapted (HA) cells were able to proliferate under an atmosphere of 99% O2/1% CO2, an O2 tension lethal to the parental (control) cells. When grown under normoxic conditions (20% O2/1% CO2/79% N2) the cells remained tolerant for at least 8 weeks, suggesting a genetic basis for the oxygen tolerance. Compared to the parental cells, the HA cells were irregularly shaped, had larger mitochondria, contained more lipid droplets and showed a reduced growth rate. Ultrastructural morphometry revealed a 1.8-fold (p less than 0.001) increase of the mitochondrial volume fraction in the HA cells, resulting from an increase in both number and average volume of the mitochondria. The volume fraction of peroxisomes was increased over two-fold in the HA cells, as appeared from a approximately 1.9-fold (p less than 0.001) increase in number and a 1.2-fold (p less than 0.025) increase in size. There was no evidence for ultrastructural damage in the HA cells. Specific activities of antioxygenic enzymes were considerably higher in the HA cells compared to controls: CuZn-superoxide dismutase, X 2.5; Mn-superoxide dismutase, X 2.1; catalase, X 4.0; glutathione peroxidase, X 1.9. Oxygen tolerance in CHO cells is therefore associated with increased levels of antioxygenic enzymes, confirming the proposed important role of these enzymes in the defense against oxygen toxicity.
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PMID:Characterization of an oxygen-tolerant cell line derived from Chinese hamster ovary. Antioxygenic enzyme levels and ultrastructural morphometry of peroxisomes and mitochondria. 396 86

Hyperoxia and gamma-irradiation were found to be mutagenic in a transformed Syrian hamster cell line in a dose-dependent manner. The frequency of resistance to 6-thioguanine increased from 10 per 10(6) survivors after 48 h of growth in 70% O2 to 32.6 (highly significant) after 75 h. Increasing the oxygen tension to 95% resulted in a significant mutagenic response in only 44 h. At equitoxic doses, gamma-irradiation was 4 times more mutagenic than 70% O2. After growth in hyperoxia, the cells showed an enhancement of catalase activity, glutathione peroxidase activity and glutathione levels but there was little effect on superoxide dismutase activity. Diethyldithiocarbamate (3 mM, 1.5 h) was mutagenic in normoxia and potentiated the mutagenic activity of both gamma-irradiation and hyperoxia. Cells thus treated showed an 855 reduction in superoxide dismutase activity. When diethyldithiocarbamate was used in conjunction with a direct-acting alkylating agent, the mutagenic response was only additive. Depletion of cellular glutathione with buthionine sulfoximine (0.2 mM) or inhibition of catalase activity with aminotriazole (100 mM) was also effective in potentiating the mutagenic response of gamma-irradiation and hyperoxia. The data demonstrates that endogenously produced activated oxygen species are mutagenic to hamster cells in culture and suggest that aerobic organisms are subject to an unavoidable background risk due to living in an oxygen atmosphere.
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PMID:Induction of 6-thioguanine-resistant mutants by hyperoxia and gamma-irradiation: effect of compromising cellular antioxidant systems. 397 18

We used a nutritional deprivation model to produce intrauterine growth-retarded (IGR) rat pups (birth weight = approximately 75% of normal). The IGR newborns evidenced a marked reduction in tolerance to greater than 95% O2 exposure: 10-day survival = 10/47 (21%) versus 18/36 (50%) for control pups, and LT50 = 7.2 days versus 10 days for controls (p less than 0.01). Various lung parameters at birth and during O2 exposure were examined to try to define why prenatal undernutrition should compromise the survival of IGR rats in hyperoxia. We found decreased lung glutathione peroxidase and glucose-6-phosphate dehydrogenase activity (with normal superoxide dismutase and catalase levels) in the IGRs at birth; decreased lung disaturated phosphatidylcholine content (even more markedly decreased in 1-day premature pups); and decreased lung surface area/body weight. These factors and other features of newborn IGRs reported in the literature may help to explain how prenatal undernutrition compromises postnatal tolerance to prolonged high-O2 exposure.
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PMID:Intrauterine growth-retarded rat pups show increased susceptibility to pulmonary O2 toxicity. 398 89

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

To test the feasibility of using liposomes to deliver therapeutic agents to the lungs, the effect of liposome-encapsulated superoxide dismutase (SOD) or catalase on pulmonary oxygen toxicity was studied in rats. The SOD or catalase was encapsulated in negatively changed multilamellar liposomes and administered directly into the trachea of adult rats, which were subsequently exposed to hyperoxia (greater than 95% O2). Response to hyperoxia was examined by studying lung SOD and catalase activities, survival rates, and lung morphology. Rats receiving liposome-encapsulated SOD or catalase showed increased levels of enzyme activities in the lung homogenates compared with those in the control groups after 24 to 72 h of hyperoxic exposure. Elevated enzyme levels in the lungs of rats treated with liposome-encapsulated SOD or catalase were accompanied by a significant improvement in survival rates after 72 h of hyperoxic exposure and less lung injury than in the other control groups.
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PMID:Protection against pulmonary oxygen toxicity in rats by the intratracheal administration of liposome-encapsulated superoxide dismutase or catalase. 401 61

Rats given disulfiram (200 mg/kg) or diethyldithiocarbamate (200 mg/kg) by intraperitoneal injection were exposed to 2 atmospheres absolute oxygen in a hyperbaric chamber or kept in normoxia. By 12 hr of hyperoxia exposure, none of the control but 30% of the disulfiram-treated and 87% of the diethyldithiocarbamate-treated rats had died. Both disulfiram and diethyldithiocarbamate administration decreased lung cytosolic superoxide dismutase activity, but the pharmacokinetics were different. At 1 hr postinjection of diethyldithiocarbamate superoxide dismutase activity was 40% decreased but returned to control activity within 13 hr (4 hr, 18% inhibited). In contrast, disulfiram administration produced a greater decrease at 4 hr (31%) than at 1 hr (16%) and was still effective at 13 hr (28% less than control). Although disulfiram did not produce as great a decrease at 1 hr as did diethyldithiocarbamate, it's effect was more persistent. In vitro, diethyldithiocarbamate inactivated superoxide dismutase at 10(-4) M, although 10(-3) M disulfiram did not cause any reduction in enzymatic activity. The contrast between the inhibition by disulfiram of lung superoxide dismutase activity in vivo and its lack of effect in vitro suggests metabolism of disulfiram to diethyldithiocarbamate. It is likely that disulfiram administration potentiates oxygen toxicity via in vivo reduction to diethyldithiocarbamate and subsequent inhibition of superoxide dismutase.
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PMID:Mechanism for the potentiation of oxygen toxicity by disulfiram. 624 85

Induction of two forms of superoxide dismutase, catalase and glutathione peroxidase, occurs very rapidly in neonatal rat lung tissue upon exposure of these animals to 94 + % normobaric oxygen. No such oxygen-mediated enzyme induction occurs in the lungs of adult rats. The aged-dependent pattern of enzyme induction correlates with the well-established age-dependent tolerance of neonatal rats to hyperoxia. Enzyme induction occurs in the lungs of neonates in only those species known to be resistant to oxygen-provoked lung damage. Compromise of oxygen-mediated enzyme induction predisposed the neonatal rats to pulmonary oxygen toxicity. These data have formed the basis of the proposal that oxygen induction of the superoxide dismutases catalase and glutathione peroxidase provides a vital part of the defense mechanism against oxygen toxicity. A biochemical mechanism of oxygen-provoked pulmonary damage has been elaborated to explain the role of each enzyme in the protection against oxygen and free radical toxicity.
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PMID:Proposed mechanism for neonatal rat tolerance to normobaric hyperoxia. 625 31

We tested the hypothesis that pulmonary indoleamine 2,3-dioxygenase (indole:oxygen 2,3-oxidoreductase (decyclizing), EC 1.13.11.17), an enzyme that consumes superoxide anion (O-2), might have an antioxidant role under conditions of hyperoxia. We measured indoleamine 2,3-dioxygenase in three experimental models in which pulmonary superoxide dismutase, catalase and glutathione peroxidase (the known antioxidant enzymes) show increased activity and are associated with greater tolerance to 96-98% O2 exposure: (1) adult rats preexposed to 85% O2 for 5-7 days; (2) neonatal rats exposed directly to greater than 95% O2; and (3) adult rats treated with bacterial endotoxin during O2 exposure. Indoleamine 2,3-dioxygenase did not increase in response to O2 exposure in any of these rat models. Conversely, in adult mice treated with endotoxin, lung indoleamine 2,3-dioxygenase activity did increase, but no protection against O2 toxicity occurred. Thus, a rise in indoleamine 2,3-dioxygenase is neither necessary nor sufficient to confer resistance to O2 toxicity. These data taken together are evidence against its having any important role in the antioxidant defense system of the lung.
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PMID:The activity of pulmonary indoleamine 2,3-dioxygenase in rats and mice is not altered by oxygen exposure. 628 1

Factors responsible for the loss of respiratory burst capacity (stimulated extracellular O2-. release) of alveolar macrophages (AM) exposed to prolonged hyperoxia were assessed. Specific pathogen-free rats were exposed to 1 ATA O2 for 24-72 h, and lungs of survivors lavaged. Release of O2-. by cells after addition of concanavalin A, which stimulated AM but not polymorphonuclear leukocytes (PMN), or digitonin, which stimulated both cell types, was measured using cytochrome c reduction +/- superoxide dismutase. O2-. release by AM declined 47.2% (P less than 0.05) after 24 h of hyperoxia and 100% after 60 h. Percent PMN in the lavage was less than 3% at 0-36 h but increased to 16% at 48 h and to 44% at 72 h. Although addition of PMN to AM in vitro caused inhibition of AM O2-. release, the percent PMN required for inhibition was not reached in vivo until after a significant decline in AM O2-.-releasing capacity had already occurred. Cell-free lavage fluid from either control or hyperoxic rats did not affect AM O2-. release. AM in culture for 24 h in hyperoxia lost 76.7% (P less than 0.005) of O2-.-releasing capacity vs. cells incubated in 20% O2, although dye exclusion was unaffected. The results indicate that the major cause of loss of AM O2-. release by hyperoxia is a direct effect of O2 on the cells.
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PMID:Hyperoxia inhibits stimulated superoxide release by rat alveolar macrophages. 629 Apr 36

Porcine lung and liver nuclei generated superoxide (O-2) at a rate which increased with increasing oxygen concentration. NADH-dependent O-2 generation increased from 0 to 2.21 +/- 0.11 nmol/min per mg protein for lung nuclei and from 0.16 +/- 0.09 to 1.34 +/- 0.14 nmol/min per mg protein for liver nuclei, when oxygen concentration increased from 0 to 100%. NADPH-dependent O-2 generation increased similarly in liver nuclei (from 0.20 +/- 0.09 to 1.20 +/- 0.12 nmol/min per mg protein), while lung nuclei produced only 0.45 +/- 0.09 nmol/min per mg protein at 100% oxygen. NADH and NADPH had an additive effect on O-2 generation by liver nuclei, yielding 2.58 +/- 0.21 nmol/min per mg protein at 100% oxygen. Very little or no superoxide dismutase activity was present in washed nuclear preparations. The oxygen-dependence of nuclear O-2 generation shows that nuclear-derived partially reduced species of oxygen may affect nuclear function during hyperoxia or other metabolic situations where overproduction of oxygen radicals is problematic.
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PMID:Hyperoxia enhances lung and liver nuclear superoxide generation. 632 74


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