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

Prenatal dexamethasone (DEX) treatment is known to accelerate the maturation of both the surfactant system and the fetal lung antioxidant enzyme (AOE) system (Frank L, Lewis P, Sosenko IRS: Pediatrics 75:569-574, 1985). Because of this stimulatory effect of prenatal DEX on the normal late gestational development of the AOE system, we questioned whether this treatment might have a salutary effect on the ability of the newborn rat to tolerate early and prolonged exposure to hyperoxia, inasmuch as the AOE are the primary lung defensive system against high O2 challenge. In nine experiments with term newborn rats in greater than 95% O2, the composite percentage of survival was significantly greater in the prenatal DEX pups at all time periods in hyperoxia from 7 d [control pups, 67 of 94 (71%); prenatal DEX, 96 of 99 (97%)] to 14 d [controls, 10 of 32 (31%); prenatal DEX, 18 of 33 (55%)] (p less than 0.01). In addition to survival per se, the prenatal DEX pups showed significantly decreased lung wet weight/dry weight ratios, pathologic evidence of pulmonary edema, and lung conjugated dienes versus the O2 control newborn group. Of the many comparative parameters examined, the major difference found between the two groups was in the pulmonary AOE responses to hyperoxia. By 2 d in hyperoxia, the prenatal DEX rat pups showed significantly elevated superoxide dismutase, catalase, and glutathione peroxidase activities compared to air control pups, and at 4 and 7 d in O2 the AOE levels were consistently greater in the DEX group than the AOE responses in the control O2 pups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prenatal dexamethasone treatment improves survival of newborn rats during prolonged high O2 exposure. 150 13

Neonatal animals of several species are more tolerant of hyperoxic exposure than are adults, but the mechanisms of increased neonatal tolerance are unknown, as are the cell types, if any, that contribute to oxygen resistance. We studied the effect of in vivo exposure to 85% oxygen for 72 h on the activities of the antioxidant enzymes, glutathione peroxidase, catalase and superoxide dismutase (SOD), in alveolar type II cells and whole lung from adult and neonatal rats. Baseline antioxidant enzyme activities were generally lower in neonatal type II cells compared with adults. Baseline enzyme activities did not differ in neonatal type II cells and lung homogenates except for lower catalase activity in type II cells. Hyperoxic exposure resulted in 35-38% increases in antioxidant enzyme activities in neonatal whole lung. In neonatal type II cells, SOD activity increased by 170% after hyperoxia, whereas catalase and glutathione peroxidase were not significantly changed. In the adult whole lung, hyperoxic exposure resulted in increases in only glutathione peroxidase activity, whereas in adult type II cells there was a significant decrease in SOD activity after O2 exposure. Therefore, although baseline antioxidant enzyme activities were not higher in neonatal type II cells compared with whole lung, there were differences in the antioxidant enzyme responses of adult and neonatal type II cells to hyperoxia, particularly with respect to SOD. The ability of the neonatal type II cell to respond to hyperoxia with an early increase in SOD activity may contribute to the enhanced oxygen tolerance of the neonate.
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PMID:The effect of hyperoxic exposure on antioxidant enzyme activities of alveolar type II cells in neonatal and adult rats. 160 20

HA-1 hamster fibroblasts receiving fresh media every 24 h were continuously passaged in progressively increasing O2 concentrations for 18 mo (designated O2R95). These cells were significantly more resistant than parental HA-1 to clonogenic inactivation mediated by 95% O2 without media replacement. The O2R95 cell line exhibited increases in the activities of catalase (CAT), Mn superoxide dismutase (MnSOD), Cu,Zn superoxide dismutase (Cu,Zn SOD), and glutathione peroxidase (GPx). O2R95 cells demonstrated uniformly distributed increased staining for CAT, MnSOD, Cu,Zn SOD, and GPx proteins, as determined by immunohistochemistry. Cellular resistance to and metabolism of 4-hydroxy-2-nonenal (4HNE), a toxic byproduct of lipid peroxidation implicated in mechanisms of O2 toxicity, was examined in HA-1 and O2R95 cell lines. O2R95 cells were significantly more resistant to 4HNE cytotoxicity, which was accompanied by a significant increase in 4HNE metabolism. O2R95 cells also demonstrated an increase in total glutathione (GSH) and glutathione S-transferase (GST) activity, an enzymatic system believed to be involved with 4HNE metabolism. Furthermore, homogenates from O2R95 cells consumed greater quantities of 4HNE in the presence of NADPH (but not NADH, NAD+, or NADP+), suggesting that an enzyme(s) utilizing NADPH contributes to 4HNE metabolism, resistance to 95% O2 and 4HNE as well as increased total GSH, antioxidant enzyme activities, and NADPH-dependent metabolism of 4HNE, persisted in O2R95 cells for 75 days of growth in 21% O2. These findings are compatible with the hypothesis that aldehydic byproducts of lipid peroxidation contribute to mechanisms of O2 toxicity and the selective pressure exerted by exposure of cells to hyperoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A stable O2-resistant cell line: role of lipid peroxidation byproducts in O2-mediated injury. 161 58

Rats were exposed to 100% O2 atmosphere for 12, 36 or 48 h, and their lungs, brain, liver and kidneys were studied for signs of oxidative damage. Oxidative damage at molecular level was estimated by: (1) the appearance of conjugated diene double bonds and (2) the amount of fluorescent chromolipids in lipids extracted from tissues. As important intracellular regulators of oxidative stress, the response of enzymes detoxifying reactive oxygen species was also studied. Macroscopically, the brain and the lungs were most susceptible to oxygen-induced effects. As an indication of oxidative tissue damage, hyperoxia caused accumulation of fluorescent chromolipids in brain and lung tissues, whereas diene conjugation did not reveal any signs of lipid peroxidation. Accumulation of fluorescent chromolipids was most prominent in the brain, where 99 and 138% increases over the control were detected after 36 and 48 h hyperoxia, respectively. Fluorescent chromolipids appeared in urine already before their concentrations were elevated in tissues. The activity of superoxide dismutase in the brain was initially decreased, followed then by a slight induction of activity at the later time-points. Pulmonary and hepatic catalase activities were markedly decreased after prolonged (36 and 48 h) hyperoxia. In conclusion, fluorescent chromolipid formation seems to be a sensitive indicator of hyperoxia-induced oxidative damage in rat tissues. The lipid peroxidation-derived fluorescent chromolipids are eliminated from the body via urinary excretion. Moreover, impaired detoxication of reactive oxygen may be implicated in tissue damage due to hyperoxia.
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PMID:Pro-oxidant effects of normobaric hyperoxia in rat tissues. 163 44

Mutants of Escherichia coli lacking superoxide dismutase (SOD) activity were used to explore the sensitivity of aconitase toward O2 and O2-. The aconitase activity in SOD-free extracts was rapidly lost under aerobic conditions and exogenous SOD afforded a concentration-dependent protection. The rate of the inactivating reaction between O2- and aconitase was estimated to be of the order of 10(9) M-1 s-1. The competitive inhibitors fluorocitrate and tricarballylate provided some protection, and at saturating concentrations, they decreased the rate of the inactivating reaction by 100- and 10-fold, respectively. Aconitase was markedly less sensitive to O2 than it was to O2-. Aerobic growth on succinate involves a greater dependence upon aconitase than does growth on glucose and, as expected, the deleterious consequences of SOD deficiency were more pronounced on succinate than on glucose. Moreover, aconitase activity was lower in extracts of aerobically grown SOD mutants, than it was in the parental strain. We suppose that inactivation of aconitase by O2- involves oxidative attack on the prosthetic iron-sulfur cluster. The extreme sensitivity of aconitase to inactivation by O2- suggests that its inactivation will be an early event in the oxidative stress imposed by hyperoxia, ultraviolet irradiation or redox-cycling agents, such as viologens or quinones.
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PMID:Superoxide sensitivity of the Escherichia coli aconitase. 165 83

The changes of free radicals and the effect of anisodamine and vitamin E on hyperoxic lung injury were studied. Ninety adult Wistar rats were exposed to greater than 95% O2. Nine a normal rats served as controls. The animals in group A were only exposed to hyperoxia, while in group B and C, they were treated intramuscularly with anisodamine (15 mg/kg, bid) and vitamin E (75 mg/kg, bid) respectively. The rats in each group were killed after 12, 24 or 48 hours oxygen exposure. The blood and lung were examined for SOD, GSH-PX and MDA. In Group A, the quantity of peroxide free radical increased 20%. The activity of SOD and GSH-PX decreased and MDA increase were in lower degree. Changes of SOD, GSH-PX, MDA, PaO2 and lung damage were also in lower degree. The results indicated that the increase of oxygen free radicals may be the pathophysiological factor in hyperoxic lung injury.
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PMID:[The mechanism of the effects of 654-2 and vitamin E on hyperoxic lung injury]. 166 87

Experiments were designed to investigate the role of oxygen tension on modulation of endothelium-derived relaxing factor/nitric oxide (EDRF/NO) synthase activity. EDRF/NO synthase from bovine cerebellum was confirmed to have cofactor and kinetic characteristics similar to that reported in endothelium and other tissues. The effect of oxygen tension on EDRF/NO synthase activity as assessed by L-[3H]citrulline production was investigated. Hypoxia markedly inhibited EDRF/NO synthase activity whereas hyperoxia increased the initial rate of enzyme activity. The inhibition of EDRF/NO synthase activity by hypoxia was reversed by normoxia as well as by hyperoxia. The Km values for L-arginine in hyperoxia, normoxia and hypoxia were 7 +/- 0.7, 4.8 +/- 0.4 and 7 +/- 1.3 microM whereas the Vmax values were 94 +/- 8, 66 +/- 7, and 32 +/- 2 pmol/min/mg of protein, respectively. The effect of oxygen tension on EDRF/NO synthase activity as determined by L-[3H]citrulline production was correlated with EDRF/NO production using a bioassay in which an EDRF/NO synthase preparation was incubated in wells of cultured vascular smooth muscle and cyclic GMP production was measured. Hypoxia almost inhibited the production of cyclic GMP completely, which was comparable to its inhibition of L-[3H]citrulline production. Hyperoxia, however, showed partial inhibition of cyclic GMP accumulation with no significant effect on L-[3H]citrulline production. This cyclic GMP inhibition by hyperoxia was reversed partially by superoxide dismutase. We conclude that hypoxia inhibits EDRF/NO synthase activity primarily through depletion of oxygen, one of the substrates for the enzyme. In hyperoxia, the initial rate of EDRF/NO synthase activity (Vmax) is significantly enhanced with no significant change in enzyme activity at longer time intervals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of endothelium-derived relaxing factor/nitric oxide synthase from bovine cerebellum and mechanism of modulation by high and low oxygen tensions. 171 81

Exposure to hyperoxia results in endothelial necrosis followed by type II cell proliferation. This suggests that type II cells are resistant to hyperoxia. Oxygen-induced lung injury may result from an overproduction of oxygen metabolites normally scavenged by antioxidants such as superoxide dismutase (SOD), glutathione peroxidase, catalase and reduced glutathione (GSH). Therefore, resistance of type II cells to hyperoxia may be linked to high antioxidant activities. To test this hypothesis we compared in vitro the effects of a 24 h exposure period to 95% O2 on cultured type II cells, lung fibroblasts and alveolar macrophages isolated from rats. We show that type II cells, when compared with other cell types, are highly sensitive to hyperoxia as shown by increased lactate dehydrogenase (LDH) release, decreased deoxyribose nucleic acid (DNA) and protein content of Petri dishes and decreased thymidine incorporation into DNA. Synthesis of dipalmitoylphosphatidylcholine was also significantly reduced. Antioxidant enzyme activities as well as glutathione content were not higher in type II cells than in other cell types. However, hyperoxia results in a decreased SOD activity and glutathione content in type II cells which was not observed in fibroblasts. We conclude that adaptative changes in SOD and glutathione metabolism could be important defence mechanisms in cells exposed to hyperoxia.
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PMID:Toxic effects of oxygen on cultured alveolar epithelial cells, lung fibroblasts and alveolar macrophages. 175 40

The ability of niacin to relieve the growth-inhibiting effect of hyperoxia on Escherichia coli can be attributed to the dioxygen sensitivity of quinolinate synthetase. The activity of this enzyme within E. coli was diminished by exposure of the cells to 4.2 atm O2, while the activity in extracts was rapidly decreased by 0.2 atm O2. Neither catalase nor superoxide dismutase afforded detectable protection against the inactivating effect of O2, indicating that H2O2 and O2- were not significant intermediates in this process. Nevertheless, H2O2 at 1.0 mM did inactivate quinolinate synthetase, even under anaerobic conditions and in the absence of catalatic activity which might have generated O2. Addition of paraquat to aerobic cultures of E. coli caused an inactivation of quinolinate synthetase, which may be explained in terms of an increase in the production of H2O2. The O2-dependent inactivation of quinolinate synthetase in extracts was gradually reversed during anaerobic incubation and this reactivation was blocked by alpha, alpha'-dipyridyl or by 1,10-phenanthroline. The sequence of the quinolinate synthetase "A" protein contains a--cys-w-x-cys-y-z-cys--sequence, which is characteristic of (Fe-S)4-containing proteins. This sequence, together with the effect of the Fe(II)-chelating agents, suggests that the O2-sensitive site of quinolinate synthetase is an iron-sulfur cluster which is essential for the dehydration reaction catalyzed by the A protein.
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PMID:Quinolinate synthetase: the oxygen-sensitive site of de novo NAD(P)+ biosynthesis. 184 9

Antioxidant enzymes, including superoxide dismutase, are important for protecting the lung against O2 injury. Manganese superoxide dismutase (Mn-SOD) is a superoxide anion (O2-.) scavenger located in the mitochondria, a primary site of O2-. production during hyperoxia. We studied the effects of tumor necrosis factor (TNF-alpha), a macrophage-derived cytokine, on Mn-SOD expression in human pulmonary adenocarcinoma cells. TNF-alpha significantly increased Mn-SOD activity and mRNA in a dose-and time-dependent manner. Mn-SOD activity was increased 3-fold and mRNA 20-fold after a 48-h incubation with TNF-alpha (25 ng/ml). To examine the mechanism of this increase, cells were incubated for 48 h with TNF-alpha (25 ng/ml) with or without cycloheximide (10 microns) or actinomycin D (10 micrograms/ml). Actinomycin D blocked the induction of Mn-SOD mRNA by TNF-alpha, but cycloheximide did not. These findings suggest that the effect of TNF-alpha requires gene transcription but not synthesis of new protein intermediates. To test the hypothesis that increased Mn-SOD protects against oxidative injury, pulmonary adenocarcinoma cells were incubated in TNF-alpha (25 ng/ml) for 48 h and then exposed to paraquat (PQ+), an intracellular O2-. generator. Cells pretreated with TNF-alpha had significantly improved survival in PQ+ compared with controls. At the LD50 (6 microns) for control cells, 95% of TNF-alpha-treated cells survived, 85% at the LD75 (10 microns), and 77% at the LD90 (14 microns). Our results suggest that the induction of Mn-SOD by TNF-alpha in pulmonary adenocarcinoma cells is pretranslationally mediated and that increasing Mn-SOD activity with TNF-alpha confers protection against O2 radicals.
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PMID:Tumor necrosis factor-alpha increases Mn-SOD expression: protection against oxidant injury. 185 Feb 7


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