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

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

Analysis is made of a complex of clinicoelectrophysiologic, biochemical and biophysical studies conducted in 220 patients with brain stroke, receiving a course of hyperbaric oxygenation (HBO) at minor differential pressure (1.2-1.3 absolute atmospheres). It is shown that HBO can be applied as pathogenetic therapy in patients afflicted with brain stroke. It produces a marked clinical effect and normalizes EEG, REG and acid-alkaline balance, brings about a decrease of initially high lipid peroxidation (LPO), activating antioxidative processes and superoxide dismutase. However, such an effect is only produced by the first HBO sessions at minor differential pressure, which is likely to be due to the substitution action of hyperoxia and activation of antioxidative processes. The studies thus made validate the efficacy of short-term sessions of HBO in patients with brain stroke and the possibility of hyperoxia over-dosage in patients with disturbed antioxidant defence.
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PMID:[Mechanisms of the therapeutic effect of hyperbaric oxygenation in minor differential pressure in stroke]. 215 24

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

Tracheal insufflation of tumor necrosis factor (TNF) enhances pulmonary antioxidant enzyme activities and protects rats against oxygen toxicity (J. Appl. Physiol. 68: 1211-1219, 1990). We now report that tracheal insufflation of TNF selectively induced pulmonary Mn-superoxide dismutase (SOD) mRNA in normoxia- and hyperoxia-exposed rats, leading to increased amounts of Mn-SOD specific protein and enzyme activity. Tracheal insufflation of TNF had no effect on the levels of pulmonary Cu,Zn-SOD mRNA or specific protein. Hyperoxia alone also selectively induced pulmonary Mn-SOD mRNA. However, the hyperoxia-induced increase in Mn-SOD mRNA was not associated with an increase in Mn-SOD specific protein or enzyme activity. The results suggest that the increased pulmonary Mn-SOD in TNF-insufflated rats may contribute to the TNF-induced protection against oxygen toxicity.
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PMID:Molecular basis for tumor necrosis factor-induced increase in pulmonary superoxide dismutase activities. 226 Jun 78

Antioxidant enzymes (catalase, superoxide dismutase and glutathione peroxidase) have been injected into human fibroblasts exposed to 2 atm O2 in order to test if the threshold of oxidative damage versus antioxidant defenses could be modulated and if the damage remains reversible beyond the threshold. Cell damage was estimated by thymidine incorporation and cell survival curves. The proportion of dividing cells, measured by thymidine incorporation, rapidly decreased after O2 incubation: no cells could divide after 15 h of hyperoxia. However, cells incubated for a short time and injected with a high concentration of any of the three enzymes divided like non-oxygen-incubated cells: the enzymes could protect the cells against their loss of division potential. However, when cells were incubated for a longer period and/or when the injected enzyme concentration was lower, cells were either less or not protected and could no longer divide. These results suggest the presence of a threshold for the oxidative damage which cannot be totally repaired and which impairs the cell division; this threshold can, however, be modulated by supplementation of antioxidant enzymes, glutathione peroxidase being the most efficient.
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PMID:Importance of a threshold for error accumulation in cell degenerative processes. I. Modulation of the threshold in a model of free radical-induced cell degeneration. 229 89

Oxidants from cigarette smoke or those produced by phagocytes are implicated in the pathogenesis of emphysema. We reasoned that augmentation of antioxidant enzymes in cigarette smokers may be important in restricting direct and indirect oxidant damage to alveolar structures. Accordingly, we studied the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSHPx), in alveolar macrophages (AM) from cigarette smokers and from smoke-exposed hamsters. The activities of these antioxidant enzymes were compared with the activities found in AM from nonsmoking control subjects. The activities of SOD and CAT from AM of smokers and smoke-exposed hamsters were twice that found in control subjects (p less than 0.01), but there was no change in the activity of GSHPx. Using the hamster model, we found that filtration of smoke attenuated the increase in antioxidant activities, and that after smoking cessation, the increased activities had returned to those found with control subjects. An adaptive response was further suggested by prolonged survival of smoke-exposed hamsters in normobaric hyperoxia (O2 greater than 95%). Chronic smoke exposure in humans or hamsters causes increased SOD and CAT activities in AM. This augmented activity may serve as a mechanism to limit oxidant-mediated damage to alveolar structures.
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PMID:Selective increase of antioxidant enzyme activity in the alveolar macrophages from cigarette smokers and smoke-exposed hamsters. 231 98

Treatment with endotoxin protects rats against lung injury during hyperoxia (greater than 98% oxygen at 1 atmosphere absolute for 60 h). This study demonstrates that serum from endotoxin-treated donor rats also protects recipients from oxygen toxicity. Rats treated with serum from saline-treated donors were not protected, and protection was not explained by residual endotoxin in protective sera. Unlike endotoxin-protected rats (where lung antioxidant enzyme activity is elevated after hyperoxia), postexposure superoxide dismutase (SOD) and catalase (CAT) activities in the lungs of serum-protected rats were not affected. Levels of tumor necrosis factor (TNF) and interleukin 1 (IL-1) in protective sera were increased. This study demonstrates that increases in lung SOD and CAT activity are not required for endotoxin protection from hyperoxia and suggests that TNF and IL-1 may participate in the mechanism of endotoxin protection.
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PMID:Endotoxin protection of rats from pulmonary oxygen toxicity: possible cytokine involvement. 231 67

Preexposure of male Lewis rats to Cd aerosols (1.6 mg Cd/m3, 3 hr/day, 5 days/week, for 4 weeks) has been found to produce a marked degree of tolerance to hyperoxia (greater than 96% O2). Cd-pretreated animals were still alive after 8 days of continuous exposure to oxygen. In contrast, hyperoxia was fatal to all air-preexposed animals within 54-62 hr. Lungs of Cd-pretreated animals were characterized by hyperplasia and/or hypertrophy of the type II alveolar cell compartment which may have enabled them to more rapidly repair oxidant damage resulting from hyperoxia. Cd pretreatment augmented enzymatic antioxidant enzyme activities, including total lung Se-dependent glutathione peroxidase, catalase, glutathione reductase, and Mn-superoxide dismutase, and caused elevations in pulmonary nonprotein thiols and metallothionein (MT). MT, a thiol-rich, low-molecular-weight protein, was 400-fold higher in Cd-pretreated animals and bound more than 80% of the total Cd in the lung. We have hypothesized that MT serves as an expendable yet renewable cellular target for free radical damage during oxygen exposure. A systemic acute-phase response, characterized by alterations in plasma Zn and Cu concentrations and increased ceruloplasmin oxidase activity, was initiated in Cd-pretreated animals by the fourth day of hyperoxia. This response was accompanied by improvement in pulmonary status and extensive pulmonary repair.
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PMID:Cross-tolerance to hyperoxia following cadmium aerosol pretreatment. 233 May 88

Two major lines of defense exist against oxidant lung injury: tissue antioxidants and antioxidant enzymes. We studied pretreatment with the antioxidants, vitamin E and butylated hydroxyanisole (BHA), and the antioxidant enzymes, superoxide dismutase (SOD) and catalase, in rabbits exposed to 100% O2 for 48 h. BHA (200 mg/kg ip) or vitamin E (50-100 mg/kg po) were given for 2 or 3 days, respectively, before O2 exposure. Combined therapy with polyethylene glycol- (PEG) conjugated SOD (12 mg/kg) and catalase (200,000 U/kg) was given intraperitoneally 1 h before and 24 h after beginning 100% O2. Hyperoxia significantly increased the pulmonary content of malondialdehyde, indicating enhanced lipid peroxidation. One hundred percent O2 also increased lung weight gain and alveolar-capillary permeability to aerosolized 99mTc-labeled diethylenetriaminepentaacetate (99mTc-DTPA, 500 mol wt) and fluorescein isothiocyanate-labeled dextran (7,000 mol wt). Pretreatment with vitamin E, BHA, or the combination of PEG-SOD and PEG-catalase prevented the increase in malondialdehyde, lung weight gain, and alveolar-capillary permeability caused by hyperoxia. These results indicate that augmenting either tissue antioxidants or antioxidant enzymes can prevent the pulmonary injury caused by 48 h of 100% O2 in rabbits.
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PMID:Antioxidants and antioxidant enzymes protect against pulmonary oxygen toxicity in the rabbit. 234 49

Deficiencies of antioxidants and increased free radical generation may explain the high incidence of bronchopulmonary dysplasia in premature infants. Long-acting antioxidants such as polyethylene glycol (PEG) conjugated superoxide dismutase (SOD), and catalase might modify this process. We delivered 32 premature lambs, 16 pairs of twins, by cesarean section at 125-141 days of gestation (term 146 days) and stabilized them on ventilators in normocapnic hyperoxia for a period of 8 h. One lamb of each twin pair received an intravenous dose of 7,500-50,000 IU/kg of PEG-SOD and of 37,500-1,000,000 IU/kg of PEG-catalase at birth. Their siblings acted as controls. Mean airway pressure, arterial pressure, and heart rate were recorded continuously. Arterial blood gases and pH were obtained every 30 min. After sacrifice, standardized lung biopsies were prepared for quantitative morphometrics and electron microscopy. Administration of PEG antioxidants at birth reduced the influx of neutrophils and macrophages into the lung and damage to arterioles, bronchiolar mucosa, and type II pneumocytes without major changes in alveolar surface area or pulmonary function. These effects were dose-related and detectable even at the lowest doses of PEG antioxidants administered.
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PMID:Mitigation of pulmonary oxygen toxicity in premature lambs with intravenous antioxidants. 235 45


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