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

Oxygen toxicity to the lung is characterized by injury of the pulmonary capillary endothelium with progressive loss of functioning alveolar-capillary units. Current concepts suggest that the risk of O2 toxicity in human subjects is greatly increased with O2 concentrations exceeding 50% to 60%, although there are no data to support a cellular basis for this apparent threshold of toxicity. Our study suggests that a cellular threshold may exist in human pulmonary endothelial cells for O2 toxicity. Hyperoxia was directly toxic to cultured human pulmonary artery endothelial (HPAE) cells, with impairment of replicative function, expressed as growth impairment (GI) index, monitored by two independent parameters: cell number determination and tritiated thymidine incorporation. Impaired cell growth occurred as early as 8 hours after beginning exposure to 95% O2 and with concentrations as low as 60% during a 48-hour incubation. For example, 60% O2 resulted in an impairment of HPAE cell growth at 48 hours with a GI index (cell number) of 37.5 +/- 2.1 (p less than 0.001, comparison with control cells in normoxia). Furthermore, 95% O2 impaired cell growth, as monitored by tritiated thymidine incorporation, as early as 8 hours after exposure (GI index of 43.6 +/- 4.9) however, the injury was completely reversible when cells were reincubated in normoxia for 6 hours (GI index of 4.2 +/- 4.7), p less than 0.001. O2 toxicity was associated with an increase in cellular glutathione levels but was not associated with a detectable loss of antioxidant enzyme activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxygen-mediated impairment of human pulmonary endothelial cell growth: evidence for a specific threshold of toxicity. 246 57

Pretreatment with the combination of tumor necrosis factor/cachectin (TNF/C) and interleukin 1 (IL-1) increased glucose-6-phosphate dehydrogenase (G6PDH), glutathione reductase (GR), glutathione peroxidase (GPX), catalase (CAT), and superoxide dismutase (SOD) activities in lungs of rats continuously exposed to hyperoxia for 72 h, a time when all untreated rats had already died. Pretreatment with TNF/C and IL-1 also increased, albeit slightly, lung G6PDH and GR activities of rats exposed to hyperoxia for 4 or 16 h. By comparison, no differences occurred in lung antioxidant enzyme activities of TNF/C and IL-1- or saline-pretreated rats exposed to hyperoxia for 36 or 52 h; the latter is a time just before untreated rats began to succumb during exposure to hyperoxia. The results raise the possibility that TNF/C and IL-1 treatment can increase lung antioxidant enzyme activities and that increased lung antioxidant enzymes may contribute to the increased survival of TNF/C and IL-1-pretreated rats in hyperoxia for greater than 72 h.
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PMID:Cytokines increase rat lung antioxidant enzymes during exposure to hyperoxia. 265 81

Instillation of exogenous surfactant into rabbits exposed to 100% O2 increases survival time and decreases alveolar epithelial injury. In this study we investigated whether rabbits with increased levels of endogenous pulmonary surfactant are more resistant to hyperoxia. Rabbits were exposed to 100% O2 for 64 h and then returned to room air for 8 days (preexposed). At this time, they had normal gas exchange and alveolar permeability to solute and increased levels of lavageable alveolar phospholipids compared with control rabbits breathing air (26 +/- 2 vs. 12 +/- 2 mumol/kg). Preexposed rabbits survived significantly longer than control rabbits when reexposed to 100% O2 (166 +/- 24 vs. 80 +/- 6 h; n = 7; P less than 0.05) and had significantly higher values of total lavageable phospholipids after 72 h in 100% O2 (15 +/- 2 vs. 5 +/- 2 mumol/kg). Controls developed arterial hypoxemia after 72 h in 100% O2. On the other hand, preexposed rabbits maintained arterial PO2 values greater than 100 Torr throughout the hyperoxic exposure and developed progressive respiratory acidosis. Specific activities of CuZn and Mn superoxide dismutase, catalase, and glutathione peroxidase in lung homogenates and isolated alveolar type II pneumocytes of preexposed rabbits were unchanged from those of controls before O2 reexposure and after 72 h in 100% O2. We concluded that 1) increases in pulmonary antioxidant enzyme specific activities are not necessary for the development of O2 tolerance in rabbits and 2) pulmonary surfactant may play a role in O2 adaptation.
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PMID:Development of O2 tolerance in rabbits with no increase in antioxidant enzymes. 273 59

We report a new protocol for inducing marked tolerance to prolonged exposure to hyperoxia in adult rats that entails the use of a single "rest period" between exposures to a usually lethal concentration of O2. Exposure of adult rats to greater than 95% O2 for 48 h followed by a rest in air, or a rest even in 50-75% O2, consistently resulted in 100% survival with evidence of only slight pulmonary edema during continuation of exposure to greater than 95% O2 for 3-7 more days (7-day survival for rats rested in room air for 24 h = 23/23; for rats rested in 50-75% O2 for 24 h = 27/27; for continuously O2-exposed control rats = 0/11). Induction of tolerance to hyperoxia was associated with significant increases in the lungs' antioxidant enzyme activities during the reexposure to greater than 95% O2 following the rest period. The molecular means by which the events in this protocol lead to increased lung antioxidant enzyme activity is only partially known, but because of the marked tolerance produced, the elucidation of the mechanisms must be important to our understanding of tolerance to hyperoxia.
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PMID:New "rest period" protocol for inducing tolerance to high O2 exposure in adult rats. 280 50

Rats were pretreated with various inducers of cytochrome P-450 before being exposed to pure normobaric oxygen (O2) in order to determine whether the inducers interfere with toxicity. The pulmonary and liver inducers beta-naphthoflavone (beta NF) and 3-methylcholanthrene (3MC) increased the survival rate and decreased the amount of pleural and lung fluid accumulation in adult rats exposed to oxygen. Phenobarbital (PB), which is essentially active in the hepatic microsomal cytochrome P-450, was less effective in counteracting oxygen toxicity. After 7 days of exposure to oxygen, none of the untreated rats survived, whereas 40, 73, and 90% survival was observed in rats treated with PB, 3MC, and beta NF, respectively. After 60 h of O2 exposure, significantly less pleural and lung fluid accumulation was observed in beta NF- and 3MC-treated rats than in untreated or PB-treated rats (p less than 0.001). Both beta NF and 3MC prevented the increase of lung peroxidation (assessed by measuring of malondialdehyde) and that of hydrogen peroxide production by lung microsomes induced by O2 exposure. These protective effects are associated with a large increase in the components of the pulmonary cytochrome P-450 system and its peroxidase activity and with an increased response to hyperoxia by lung antioxidant enzyme activities. In contrast, in control rats, the activities of the antioxidant enzymes were not increased, and both the quantity and the peroxidase activity of cytochrome P-450 were significantly decreased by O2 exposure. We conclude that in the rat, pretreatment by inducers of pulmonary cytochrome P-450 results in marked protection against O2 toxicity and an increase of antioxidant enzyme response to hyperoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protection of rat from oxygen toxicity by inducers of cytochrome P-450 system. 283 Aug 13

1. Small mammals have been used to study the effects of O2 toxicity. The aim of the present study was to investigate whether body size should be considered when applying the results of these studies to man. 2. Oxygen toxicity is enhanced as perfusion and metabolism increase: specific animal tissues of high perfusion are more susceptible to O2 toxicity. Exercise, high metabolic rate, and increased brain blood flow enhance O2 toxicity. 3. Increased specific O2 consumption and perfusion as body mass decreases may enhance O2 toxicity in small mammals. 4. Survival time in normobaric hyperoxia (1 atm O2) and the time to first appearance of convulsions in hyperbaric oxygen (4-5 atm) were collected from the literature and showed no relation to body size. 5. Known difference in antioxidant enzyme activity cannot explain the findings. 6. Independence of tissue PO2 on body size, or equal rates of free radical formation and degradation, are suggested as possible mechanisms. 7. Small mammals can serve as a good model for O2 toxicity in man.
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PMID:Oxygen toxicity is not related to mammalian body size. 290 37

The activity of antioxidant enzymes were measured in alveolar type II cells isolated from control and 85% oxygen-exposed rats to determine if type II cells, an oxygen-resistant lung cell type had constitutively high enzyme activities and to measure the effect of hyperoxia on these antioxidant enzyme. Type II cells were isolated from lungs of control rats and rats exposed to 85% O2 for 7 days. In whole lungs of rats exposed to 85% oxygen there is an increase in activity (per lung or per mg lung DNA) in the antioxidant enzymes CuZn superoxide dismutase, Mn superoxide dismutase, catalase, glutathione peroxidase and glucose-6-phosphate dehydrogenase. Oxygen exposure significantly increased (p less than 0.05) all type II cell antioxidant enzyme activities when expressed per mg DNA. The protein content of oxygen exposed type II cells increased 25% from (63.9 +/- 4.8 micrograms/10(6) cells to 79.6 +/- 4.2 micrograms/10(6) cells, p less than 0.05). When type II cell enzyme activities were expressed in U/mg cell protein, only CuZn superoxide dismutase and Mn superoxide dismutase increased in activity following oxygen exposure (by 43% and 28% relative to air exposed lung type II cells, respectively, p less than 0.05). This suggested that most lung cell antioxidant enzymes increased in activity following oxidant stress in proportion to increased cell mass. CuZn and Mn superoxide dismutase increased activity to an extent greater than the increase in type II cell protein content after oxygen exposure. Alveolar macrophages lavaged from control and oxygen-exposed rats were also evaluated, and they had no significant change in CuZn and Mn superoxide dismutase activities. Type II cells accounted for 10% and 17% of alveolar cells in control and oxygen treated rats. By knowing the antioxidant enzyme activities in type II cells, the total enzyme activity of whole lung and the number of type II cells in control and oxygen exposed rats from morphometric data, we calculated the percent of whole lung enzyme activity accounted for by type II cells. Type II cells accounted for a high percentage of lung glucose-6-phosphate dehydrogenase (58% in control rats, 65% in oxygen exposed rats) but a low percentage of Mn superoxide dismutase (4% in control rats, 6% in oxygen exposed rats).
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PMID:Antioxidant enzyme activity in alveolar type II cells after exposure of rats to hyperoxia. 300 82

The failure of adult rats to survive prolonged exposure to greater than 95% O2 is generally ascribed to the inability of their lungs to increase antioxidant enzyme synthesis in response to the oxidant challenge. We studied the synthesis rate of the antioxidant enzyme CuZn superoxide dismutase (CuZn SOD) in lungs of adult and neonatal rats exposed to conditions that alter the lung's oxidant-to-antioxidant balance. Lung CuZn SOD synthesis in the adult was significantly increased after 24 h of hyperoxia but fell to control levels after further exposure, whereas in neonatal lungs an increased rate of synthesis of CuZn SOD was found only after 72 h of hyperoxia. The adult lung responded to two in vitro oxidant stresses, [diethyldithiocarbamate exposure and heat (42 degrees C)] with increases in CuZn SOD synthesis twice the magnitude of those in the neonatal lung. These data indicate that the adult lung is at least as capable as the neonatal lung of increasing its synthesis of CuZn SOD in response to an oxidative stress. However, the inability of the adult lung to maintain an increased rate of CuZn SOD synthesis during in vivo hyperoxia may contribute to the poor tolerance of the adult lung to greater than 95% O2.
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PMID:Differences in CuZn superoxide dismutase induction in lungs of neonatal and adult rats. 303 15

Preexposure of rats to sublethal levels of hyperoxia or ozone reduces morbidity and mortality when the animals are subsequently exposed to lethal levels of either oxidant stress. Lung homogenates and isolated type II pneumocytes from rats exposed to these oxidant stresses demonstrate enhanced antioxidant enzyme activities. Antioxidant enzymes, superoxide dismutase, catalase, and glutathione peroxidase are responsible for the detoxification of partially reduced oxygen species, superoxide and hydrogen peroxide, to less reactive states. Potential pulmonary cellular loci of partially reduced oxygen include mitochondrial NADH dehydrogenase, endoplasmic reticulum-derived NADPH cytochrome c reductase, and cytosolic xanthine oxido reductase. Thus partially reduced oxygen species are hypothesized to mediate hyperoxia and ozone-induced pulmonary damage. This damage may be attenuated by enhanced intracellular antioxidant enzyme activities. Pharmacologic augmentation of pulmonary antioxidant enzymes may be accomplished via intratracheal or intravascular delivery of liposomes containing antioxidant enzymes. Rats pretreated with liposomes containing both superoxide dismutase and catalase, when subsequently exposed to lethal levels of hyperoxia, demonstrate enhanced survival compared with control animals or with animals treated with control liposomes or native antioxidant enzymes. Finally, knowledge obtained from in vitro investigations optimizing liposomal delivery to specific pulmonary cell types may further aid in reducing in vivo pulmonary damage to hyperoxia and ozone.
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PMID:Pulmonary metabolism of reactive oxygen species. 306 93

Buthionine sulfoximine (BSO), an inhibitor of de novo synthesis of glutathione (GSH), was used to deplete rats of GSH and determine the effect of treatment on antioxidant enzyme responses, lung injury, and the susceptibility to concurrent sublethal or lethal hyperoxia. In a preliminary experiment, total lung nonprotein sulfhydryl (NPSH) and GSH levels were measured at various times after single doses of BSO. The lowest concentrations were observed at 12 to 18 h. These experiments were used to establish a repeated dosing protocol for more prolonged GSH depletion. The lungs of rats treated with BSO for 4 days demonstrated markedly decreased GSH and NPSH levels (10 to 40% of control values) and glutathione peroxidase activity (45 to 60% of control values). Superoxide dismutase activities were elevated, glutathione reductase activity was slightly elevated, and catalase activity was unchanged. These changes were dose-responsive. The lungs of treated rats were grossly and microscopically normal. BSO treatment of additional rats did not increase susceptibility to lethal hyperoxia (greater than 98% oxygen). Combined treatment of rats with both BSO and sublethal hyperoxia (80% oxygen) for 4 days did not alter the biochemical responses demonstrated by rats treated solely with BSO. The marked increase in catalase activity obtained after hyperoxia alone was not observed in rats treated with both hyperoxia and BSO. The lungs of saline- and BSO-treated rats exposed to sublethal hyperoxia demonstrated a patchy distribution of slight perivascular and peribronchiolar edema.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The pulmonary effects of buthionine sulfoximine treatment and glutathione depletion in rats. 320 1


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