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

Exposure to hyperoxia causes loss of alveolar macrophage cell function. Toxicity was measured as suppression of the respiratory burst stimulated by phorbol myristate acetate subsequent to exposure (43.5% depression by 2-h exposure to 5 atm absolute O2 vs. controls). The presence of extracellular glutathione significantly protected these cells (7% loss). gamma-Glutamyl transpeptidase, a membrane enzyme with its active site directed outward, was necessary for use of extracellular glutathione. This was demonstrated using the gamma-glutamyl transpeptidase inhibitor, serine-borate complex, which significantly blocked both protection of cells by extracellular glutathione and extracellular glutathione-dependent synthesis of glutathione. The principal use of glutathione in antioxidant defense is as a substrate for glutathione peroxidase. The apparent Km for glutathione of glutathione peroxidase of rat alveolar macrophages was determined to be 2 mM; however, rat alveolar macrophages have approximately 1.3 mM intracellular glutathione, which is insufficient for maximal enzymatic activity. During hyperoxic exposure, this deficit would probably be more significant. Thus the ability of extracellular glutathione along with gamma-glutamyl transpeptidase activity to provide amino acids for de novo glutathione synthesis appears to be a potentially important component of antioxidant defense.
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PMID:Protection of alveolar macrophages from hyperoxia by gamma-glutamyl transpeptidase. 197 90

The effects of hyperoxia and the response of oxygen free radical defense enzymes in the lung and extracellular environment of the lung were measured in Zn-deficient rats. Although lung was the target organ as indicated by the increased lung:body weight ratio in all hyperoxia-exposed rats regardless of dietary regimen, 85% oxygen exposure seemed to impose a stress on the whole animal as indicated by decreased feed intake and body weight in ad libitum-fed rats. Hyperoxia exposure superimposed on Zn deficiency did not further reduce the feed intake or body weight of Zn-deficient rats. After 7 d of hyperoxia exposure, the Zn-repleted and ad libitum-fed groups consistently had increased activity of lung CuZn-superoxide dismutase (CuZnSOD), glutathione peroxidase and catalase; but changes in CuZnSOD activity were not related to lung Cu or Zn concentrations. Although Zn-deficient and pair-fed rats were unable to increase CuZnSOD activity, they had an increased lung Zn concentration compared with their air-exposed counterparts. Hyperoxia exposure also caused an increase in ceruloplasmin activity of pair-fed and ad libitum-fed control rats. We concluded that dietary Zn repletion started at the beginning of 85% oxygen exposure was effective for increasing the activity of the lung oxygen free radical defense enzymes, thus preventing hyperoxia-induced lung damage in Zn-deficient rats.
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PMID:Effect of hyperoxia on oxygen free radical defense enzymes in the lung of zinc-deficient rats. 200 99

Although the prematurely born are known to have decreased baseline levels of protective antioxidant enzymes (Frank L, Sosenko IRS: J Pediatr 110:9 and 106, 1987), the ability to augment the baseline values during high O2 exposure is the key factor determining O2 tolerance versus O2 susceptibility. We have compared the pulmonary antioxidant enzyme responses of prematurely delivered rabbits (gestational d 29 of 32) and full-term rabbits to 48-72 h of hyperoxic exposure. We found that although full-term newborns exposed to greater than 90% O2 consistently showed elevated superoxide dismutase, catalase, glutathione peroxidase, and glucose-6-phosphate dehydrogenase activities, the premature animals repeatedly failed to respond to hyperoxia with increased antioxidant enzyme activity levels. Consistent with the comparative antioxidant enzyme responses were the evidences of O2 toxicity in the two age groups. The prematurely born rabbits had significantly increased lung lavage protein content, lung conjugated diene levels, and more severe light microscopic lung pathology compared with the full-term animals during equal O2 exposure time. This first reported comparison of prematurely born versus full-term animal responses to hyperoxia might help to explain the clinical observation that the very prematurely born infant is excessively prone to the development of O2-induced lung injury and the progressive development of bronchopulmonary dysplasia.
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PMID:Failure of premature rabbits to increase antioxidant enzymes during hyperoxic exposure: increased susceptibility to pulmonary oxygen toxicity compared with term rabbits. 203 78

To test the hypothesis that increases in lung superoxide dismutase can cause tolerance to pulmonary oxygen toxicity, we studied transgenic mice which constitutively express elevated levels of the human copper-zinc SOD (CuZnSOD). Upon exposure to hyperoxia (greater than 99% O2, 630 torr) the transgenic CuZnSOD mice showed increased survival, decreased morphologic evidence of lung damage such as edema and hyaline membrane formation, and reduction in the number of lung neutrophils. During continuous exposure to oxygen, both control and transgenic animals who successfully adapted to hyperoxia showed increased activity of lung antioxidant enzymes such as glutathione peroxidase (GPX), glutathione reductase (GR), and glucose-6-phosphate dehydrogenase (G6PD), whereas superoxide dismutase activity remained unchanged. The results show that expression of elevated levels of CuZnSOD decreases pulmonary oxygen toxicity and associated histologic damage and mortality.
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PMID:Transgenic mice with expression of elevated levels of copper-zinc superoxide dismutase in the lungs are resistant to pulmonary oxygen toxicity. 204 Jun 98

Replacement of media in cell cultures during exposure to hyperoxia was found to alter oxygen toxicity. Following 100 hr of exposure to 95% or 80% O2, the surviving fraction (SF) of Chinese hamster fibroblasts, as assayed by clonogenicity, was less than 1 x 10(-3) when the culture media was replaced only at the onset of the O2 exposure. Media replacement every 24 hr throughout the hyperoxic exposure resulted in SFs of 1.7 x 10(-1) (95% O2) and 1.9 x 10(-1) (80% O2) at 95 hr. Cellular resistance to and metabolism of 4-hydroxy-2-nonenal (4HNE), a cytotoxic byproduct of lipid peroxidation, was examined in cells 24 hr following exposure to 80% O2 for 144 hr with media replacement. These O2-exposed cells were resistant to 4HNE, requiring 2.6 times as long in 80 microM 4HNE to reach 30% survival as compared to density-matched normoxia control. Furthermore, during 40 and 60 min of exposure to 4HNE, the O2-preexposed cells metabolized greater quantities of 4HNE (fmole/cell) relative to control. The activity of glutathione S-transferase (GST), an enzyme believed to be involved with the detoxification of 4HNE, was significantly increased in the O2-preexposed cells compared with controls. Catalase activity was significantly increased, but no change was found in total glutathione content, glutathione peroxidase, manganese superoxide dismutase, and copper-zinc superoxide dismutase activities at the time of 4HNE treatment in the O2-preexposed cells relative to density-matched control. The results demonstrate that in vitro tolerance to the cytotoxic effects of hyperoxia can be achieved through media replacement during O2 exposure. Tolerance to oxygen toxicity conferred resistance to the cytotoxic effects of 4HNE, possibly through GST-catalyzed detoxification. These results provide further support for the hypothesis that toxic aldehydic byproducts of lipid peroxidation contribute to hyperoxic injury.
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PMID:Replacement of media in cell culture alters oxygen toxicity: possible role of lipid aldehydes and glutathione transferase in oxygen toxicity. 206 63

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

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

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

Female Wistar rats (n = 11) received bleomycin 10 mg kg-1 i.p. three times weekly for 6 weeks. Four weeks later part of the group (n = 7) were exposed to 50% oxygen in air for 4 h; the others served as unexposed controls. A further control group (n = 5) received physiological saline i.p. and was not exposed to oxygen. One week after the hyperoxia treatment all animals were sacrificed and the lungs prepared for histological and biochemical determinations. Although the average body weight of the bleomycin-treated rats decreased significantly compared with the saline-treated controls, no significant alterations in lung histology were found in regard to the occurrence of oedema, fibrosis, and type II pneumocytes. Intra-alveolar macrophages were significantly increased. Subsequent hyperoxia did not lead to a more pronounced effect, except for macrophage accumulation. The activities of superoxide dismutase and glutathione peroxidase were not changed either after administration of bleomycin alone or after combination with hyperoxia. It is concluded that bleomycin i.p. in doses comparable to those encountered clinically, administered alone or combined with hyperoxia, does not result in pulmonary damage in female Wistar rats.
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PMID:Pulmonary toxicity after treatment with bleomycin alone or in combination with hyperoxia. Studies in the rat. 244 26


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