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

O2 toxicity of the central nervous system (CNS) may be a result of enhanced generation of reactive O2 species such as superoxide and H2O2 at high PO2. In this study, we measured H2O2 production in six regions of the rat brain before and after convulsions induced by hyperbaric hyperoxia (HBO). H2O2 concentration was determined ex vivo using a method based on the H2O2-dependent decline in catalase activity in the presence of the irreversible inhibitor of compound I, 3-amino-1,2,4-triazole. Regional catalase activity in the brain ranged from 0.029 +/- 0.004 to 0.055 +/- 0.004 mumol O2.min-1.micrograms DNA-1 in cerebellum and medulla-pons, respectively. In the presence of aminotriazole, catalase activity declined after HBO-induced convulsions to 26-45% of normoxic values. The rates of inactivation of catalase were used to predict average steady-state values for H2O2 concentration in different brain structures. Estimated H2O2 concentrations during HBO varied from 31 to 51 pM in cerebellum and posterior subcortex and represented increases of 2.2-7.3 times normoxic values. These findings suggest that H2O2 is an important mediator of selective neuronal vulnerability to CNS O2 toxicity.
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PMID:Regional H2O2 concentration in rat brain after hyperoxic convulsions. 227 69

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

In order to clarify the physiological role in vivo of H2O2-detoxifying enzymes at low and high levels of O2 tension we studied catalase (CAT), glutathione peroxidases (GP), and in vivo peroxidation (TBA-RS) in the lung and heart of Rana perezi frogs chronically treated with hyperoxia, aminotriazole (AT) -a CAT inhibitor-, or both. Hyperoxia did not change CAT, GP or TBA-RS. Aminotriazole caused an almost complete depletion of CAT, a 30% decrease of GP and a 132% (lung) to 200% (heart) increase of TBA-RS. Changes similar to these were found in the group treated with AT in hyperoxia. No mortality or changes in total or organ weight occurred in the experimental groups. Main conclusions are: (1) The maximal hyperoxia tolerance showed by frogs among vertebrates does not need antioxidant enzyme induction from lung or heart and is probably related to the presence of high constitutive levels of GP in relation to metabolic rate. (2) Even in normoxia the tissues present significant amounts of H2O2, and CAT is needed to avoid oxidative damage. GP does not compensate its absence. The implications of these results in relation to oxygen toxicity in man is discussed.
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PMID:Aminotriazole effects on lung and heart H2O2 detoxifying enzymes and TBA-RS at two pO2. 230 4

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

The purpose of this study was to determine whether pretreatment of rabbits with bleomycin would modify their response to 100% O2 and, if so, to identify the mechanism of this action. A single intratracheal injection of bleomycin (5 U/kg) resulted in a transient decrease of the arterial Po2, its mean value (+/- SE) 7 days postinjection being 59 +/- 3 Torr. All animals were either killed or exposed to 100% O2 35 days postinjection. At this time, arterial Po2 had returned to its control level. On the other hand, lung hydroxyproline content had doubled and static compliance and the total lung capacity had decreased by 22 and 31%, respectively, indicating the existence of significant lung fibrosis. Furthermore, activities of catalase and superoxide dismutase in lung homogenates were higher than control and were further augmented by exposure to 100% O2 for 64 h. These biochemical changes may account, at least in part, for the mitigation of the toxic effects of hyperoxia, as shown by the delayed appearance of arterial hypoxemia, and the 50% increase in survival time when bleomycin injected rabbits were exposed to 100% O2 35 days postinjection.
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PMID:Modification of pulmonary oxygen toxicity by bleomycin treatment. 240 69

Cultured type II pneumocyte responses to in vitro normoxia (95% air:5% CO2) or hyperoxia (95% O2:5% CO2) were quantified. Normoxic culture (0 to 96 h) of rabbit type II cells resulted in enhanced cell-monolayer protein and DNA content. During this same time, cellular activities of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH Px) decreased. Compared to cultures maintained in normoxia, hyperoxic exposure of cultures resulted in decreased cell-associated protein and DNA content. Exposure to hyperoxia also resulted in cytotoxicity as demonstrated by elevated cellular release of DNA, lactate dehydrogenase (LDH), and preincorporated 8-[14 C]adenine. Cellular catalase and GSH Px activities in hyperoxic cells decreased similarly to normoxic controls. In contrast, cellular SOD activity in hyperoxic cells decreased less than in normoxic cultures. Cellular SOD activity in hyperoxic cultures, when normalized for cellular protein, but not DNA, was greater than normoxic values after 24 to 96 h of exposure. Unlike the decrease in cellular antioxidant enzymes during normoxic and hyperoxic culture, cellular LDH activity increased during both these exposures. Cellular LDH activity in 24 to 96 h hyperoxia-exposed cells increased to a lesser extent than normoxic controls. The extent of depression in LDH activity was dependent on whether the activity was normalized for cellular protein or DNA. Type II pneumocytes, which normally undergo hyperplasia and hypertrophy during hyperoxia in vivo, exhibited oxygen sensitivity in vitro. Exposure of type II cells to hyperoxia in vitro resulted in alterations in cellular SOD and LDH activities, but recognition of such changes were dependent on whether enzymatic activities were normalized for cellular DNA or protein.
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PMID:Responses of type II pneumocyte antioxidant enzymes to normoxic and hyperoxic culture. 250 12


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