Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Further characteristics of an oxygen-tolerant variant of Chinese hamster ovary cells (CHO-99) capable of stable proliferation at 99% O2/1% CO2, and O2 level that is lethal to the parental line (CHO-20), are described. Previous work has revealed that CHO-99 cells have 2- to 4-fold increased activities of superoxide dismutases, catalase and glutathione peroxidase, and substantially increased relative volumes of mitochondria and peroxisomes. To document possible additional mechanisms of O2 tolerance we compared CHO-20 cells growing at 20% O2 (normoxia) and CHO-99 cells at 99% O2 (normobaric hyperoxia). We show the following: (1) the estimated total (oxidative and glycolytic) ATP production in CHO-99 cells was 36% decreased. ATP production through oxidative phosphorylation was 52% lower in CHO-99 cells, while the relative contribution from glycolysis was increased from 6% to 30%. The ATP content was 29% lower in CHO-99 cells, the adenylate energy charge being also significantly decreased, indicating that energy production through oxidative phosphorylation is compromised in CHO-99 cells. Cyanide-resistant respiration was 4-fold higher in CHO-99 cells, probably reflecting, at least partly, the increased peroxisomal activity in these cells. (2) The level of reduced glutathione was several fold increased in CHO-99 cells, oxidized glutathione being unaltered; (NADPH + NADP+) levels were elevated 2.7-fold, while the ratio of NADPH to NADP+ was increased almost two-fold. These changes were associated with a 50% increased metabolism of glucose through the hexose monophosphate pathway. (3) No evidence was obtained for an increased steady-state level of endogenous lipid peroxidation in CHO-99 cells, in spite of a 50% increased content of polyunsaturated fatty acids in the phospholipid fraction.
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PMID:Characterization of oxygen-tolerant Chinese hamster ovary cells. II. Energy metabolism and antioxidant status. 338 44

Single, preexposure, parenteral injection with both recombinant tumor necrosis factor/cachectin (TNF/C) and interleukin-1 (IL-1) prolonged the survival of rats (144 +/- 9 h) in continuous hyperoxia (greater than 99% O2 at 1 atm) when compared with rats injected with boiled TNF/C and boiled IL-1 (61 +/- 2 h), TNF/C alone (61 +/- 2 h), IL-1 alone (62 +/- 2 h), or saline (64 +/- 3 h). After exposure to hyperoxia for 52 h, pleural effusion volume, pulmonary artery pressure, total pulmonary resistance, and lung morphologic damage were decreased in those rats given TNF/C and IL-1 as compared with saline-injected rats. In parallel, ratios of reduced (GSH) to oxidized (GSSG) glutathione were greater (P less than 0.05) in lungs of TNF/C + IL-1-injected rats (91 +/- 20) than of saline-injected rats (30 +/- 4) that had been exposed to hyperoxia for 52 h. No differences were found in superoxide dismutase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase, or catalase activities in lungs of TNF/C + IL-1- or saline-treated, hyperoxia-exposed rats. Our results indicate that pretreatment with TNF/C and IL-1 favorably altered lung glutathione redox status, decreased lung injury, and enhanced survival of rats exposed to hyperoxia.
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PMID:Recombinant tumor necrosis factor/cachectin and interleukin 1 pretreatment decreases lung oxidized glutathione accumulation, lung injury, and mortality in rats exposed to hyperoxia. 349 53

Monolayer cultures of fetal rat mixed lung cells respond to sublethal concentrations (50%) of oxygen by a reduced growth rate. Exposure to 95% O2 causes growth arrest and cell loss. In the presence of serum the addition of dexamethasone (5.5 nM), tri-iodothyronine (5.5 nM), or insulin (5 microU/ml) appeared to increase the cytotoxicity of 95% O2. Under growth-arrested conditions, in the absence of serum or elevated O2 concentrations, all three agents influence cellular antioxidant enzyme activities. Dexamethasone (0.055 nM) increased CuZn superoxide dismutase activity by 72% and glutathione peroxidase activity by 94%. Triiodothyronine (5.5 nM) increased CuZn superoxide dismutase activity 93%. Insulin (5 microU/ml) increased CuZn superoxide dismutase activity 90%, and catalase activity 58%. Dexamethasone, but not tri-iodothyronine or insulin, seems to have a protective effect against subsequent acute hyperoxia under serum-free conditions. Local non-hormonal factors may also influence lung cell responses to acute increases in oxygen concentrations, since cells acutely exposed to 50% or 95% O2 release a transferable factor(s) into their culture medium which increases antioxidant enzyme activities of non-hyperoxic lung cells.
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PMID:Hormonal and local factors influence antioxidant enzyme activity of rat fetal lung cells in vitro. 352 18

Superoxide dismutase is considered important in protection of aerobes against oxidant damage, and increased tolerance to oxidant stress is associated with induction of this enzyme. However, the importance of superoxide dismutase in this tolerance is not clear because conditions which promote the synthesis of superoxide dismutase likewise affect other antioxidant enzymes and substances. To clarify the role of superoxide dismutase per se in organismal defense against oxidant-generating drugs, we employed Escherichia coli transformed with multiple copies of the gene for bacterial iron superoxide dismutase. These bacteria have greater than ten times the superoxide dismutase activity of wild-type E. coli but, importantly, are normal in other oxidant defense parameters including catalase, peroxidases, glutathione, and glutathione reductase. High superoxide dismutase and control bacteria were exposed to the O2- -generating drug paraquat and to elevated pO2. We find; high superoxide dismutase E. coli are more readily killed by paraquat under aerobic, but not anaerobic, conditions. During exposure to paraquat, high superoxide dismutase E. coli accumulate more H2O2. Coincidentally, the reduced glutathione content of high superoxide dismutase E. coli declines more than in control E. coli. E. coli with high superoxide dismutase activity are also more readily killed by hyperoxia. Interestingly, the susceptibility of the parental and high superoxide dismutase E. coli to killing by exogenous H2O2 is not significantly different. Thus, under these experimental conditions, greatly enhanced superoxide dismutase activity accelerates H2O2 formation. The increased H2O2 probably accounts for the exaggerated sensitivity of high superoxide dismutase bacteria to oxidant-generating drugs. These results support the concept that the product of superoxide dismutase, H2O2, is at least as hazardous as the substrate, O2-. We conclude that effective organismal defense against reactive oxygen species may require balanced increments in antioxidant enzymes and cannot necessarily be improved by increases in the activity of single enzymes.
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PMID:Superoxide dismutase-rich bacteria. Paradoxical increase in oxidant toxicity. 354 14

Whereas guinea pigs have advanced prenatal morphological lung development, their surfactant development is not "precocious" compared with other small laboratory animals. To investigate whether maturation of the antioxidant enzyme (AOE) system coincides more closely with surfactant development or with morphological maturation, we assayed fetal guinea pig lungs at gestational days 49-69 for superoxide dismutase, catalase, and glutathione peroxidase activities. We found that elevations in pulmonary AOE occurred in parallel with increases in surfactant during the final 10-15% of gestation. Since newborn guinea pigs behave more like adult animals in their relative intolerance to hyperoxia, we explored whether prematurely delivered guinea pigs would tolerate high O2 exposure better than full-term newborns. We found that prematures have markedly improved hyperoxic tolerance compared with newborns (time at which 50% of animals died in greater than 95% O2, 6.4 days vs. 4.5 days, respectively, P less than 0.05); and (unlike newborns) premature pups are capable of mounting an elevated AOE response to hyperoxic challenge. Thus premature guinea pigs behave more like full-term newborns of other species in respect to hyperoxic tolerance, an additional precocious feature of guinea pig development.
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PMID:Guinea pig lung development: antioxidant enzymes and premature survival in high O2. 356 1

Adult rats were exposed to room air, 50%, 65%, or 80% oxygen for 6 wk. Subsets were sacrificed periodically in order to establish alterations in growth parameters and lung antioxidant responses. Prolonged exposure to 50% or 65% oxygen did not result in weight loss or changes in lung-to-body weight ratios relative to control values. Treatment with 50% oxygen produced delayed increases in nonprotein sulfhydryl (NPSH) content and catalase (CAT) activity, while treatment with 65% oxygen produced delayed increases in NPSH, CAT, and glutathione peroxidase (GPx) content. Rats treated for 6 wk with either 50% or 65% oxygen died significantly earlier than room-air control animals when these groups were subsequently exposed to 100% oxygen. Rats exposed to 80% oxygen had significantly decreased body weight, increased lung-to-body weight ratios, and increased levels of NPSH, CAT, GPx, total superoxide dismutase, and glutathione reductase by 11 days of treatment. At 6 wk they had significantly altered growth parameters and increased GPx catalase, and NPSH levels. Their final antioxidant profile was not significantly different from 65% oxygen-exposed rats. However, these animals survived significantly longer than any group when exposed to 100% oxygen. In summary, lower concentrations of sublethal hyperoxia (less than or equal to 65%) were capable of eliciting significant antioxidant enzyme responses. Levels of antioxidant enzymes in the lungs of rats chronically exposed to sublethal hyperoxia did not appear to be solely responsible for enhanced survival in subsequent lethal hyperoxia.
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PMID:Adaptation to chronic hyperoxia. Biochemical effects and the response to subsequent lethal hyperoxia. 357

An animal model was established to study the toxic effects of hyperoxia and the consequent changes in intracellular antioxidant status. Superoxide dismutase, catalase and glutathione peroxidase activities were measured in erythrocytes, liver and lung, in addition to cellular glutathione concentrations and its associated metabolism. Overt cellular damage was assessed biochemically by measurement of lipid peroxidation, hydrogen peroxide-induced haemolysis and osmotic fragility. Pathological changes were assessed by light and electron microscopy. Up to 11 days exposure of rats to 80% oxygen was not lethal, but resulted in overt cellular damage to red blood cells (haemoglobin concentration decreased from 13.8 +/- 1.4 (SD) g dl-1 to 12.4 +/- 0.5 g dl-1; hydrogen peroxide-induced haemolysis increased from 7.7 +/- 1.6% to 75.1 +/- 13.5% after 11 days of hyperoxia) and to cells of lung (4-fold increase in lipid peroxidation) as well as a biochemical adaptation to the increased concentration of oxygen metabolites (superoxide dismutase increased 3-fold, catalase 5-fold and glutathione peroxidase 2-fold). It is suggested that red cell hydrogen peroxide-induced haemolysis and reduced glutathione concentration may be useful indicators of oxidant stress in the clinical situation.
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PMID:Tissue responses to hyperoxia. Biochemistry and pathology. 360 20

Hyperoxia and hyperbaric hyperoxia increased the rate of cerebral hydrogen peroxide (H2O2) production in unanesthetized rats in vivo, as measured by the H2O2-mediated inactivation of endogenous catalase activity following injection of 3-amino-1,2,4-triazole. Brain catalase activity in rats breathing air (0.2 ATA O2) decreased to 75, 61, and 40% of controls due to endogenous H2O2 production at 30, 60, and 120 min, respectively, after intraperitoneal injection of 3-amino-1,2,4-triazole. The rate of catalase inactivation increased linearly in rats exposed to 0.6 ATA O2 (3 ATA air), 1.0 ATA O2 (normobaric 100% O2) and 3.0 ATA O2 (3 ATA 100% O2) compared with 0.2 ATA O2 (room air). Catalase inactivation was prevented by pretreatment of rats with ethanol (4 g/kg), a competitive substrate for the reactive catalase-H2O2 intermediate, compound I. This confirmed that catalase inactivation by 3-amino-1,2,4-triazole was due to formation of the catalase-H2O2 intermediate, compound I. The linear rate of catalase inactivation allows estimates of the average steady-state H2O2 concentration within brain peroxisomes to be calculated from the formula: [H2O2] = 6.6 pM + 5.6 ATA-1 X pM X [O2], where [O2] is the concentration of oxygen in ATA that the rats are breathing. Thus the H2O2 concentration in brains of rats exposed to room air is calculated to be about 7.7 pM, rises 60% when O2 tension is increased to 100% O2, and increases 300% at 3 ATA 100% O2, where symptoms of central nervous system toxicity first become apparent. These studies support the concept that H2O2 is an important mediator of O2-induced injury to the central nervous system.
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PMID:Hyperoxia increases H2O2 production by brain in vivo. 362 37

Studies about the proposed antioxidant physiological role of the catalase (CAT) enzyme in relation to different environmental oxygen tensions are reported for the first time in amphibian larvae of Discoglossus pictus and Rana ridibunda perezi during their development. The CAT levels of whole tadpoles increased constantly in both species during the larval period, reaching a maximum during the metamorphic climax. All through development, CAT activity levels were always greater in D. pictus than in R. ridibunda perezi. This correlates well with the already reported higher SOD activity and hyperoxia resistance of the D. pictus species when compared to R. ridibunda perezi. Long-term acclimation to different levels of hyperoxia (40, 60, and 100% O2) showed dose-related increases in the CAT activity of D. pictus tadpoles. These increases did not take place when the animals were subjected to acute hyperoxia (24 h). The increase in CAT activity observed after 15 days of acclimation to acute hyperoxia (710 mm Hg: 100% O2) was reversed after 15 additional days of postacclimation to normal air (149 mm Hg O2). When recently metamorphosed frogs were acclimated to acute hyperoxia, significant increases in CAT activity were observed after 15 days, but not after 7 days. The results are interpreted as supporting a protective role for the CAT enzyme in amphibian larvae and froglets against oxygen toxicity.
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PMID:Different levels of hyperoxia reversibly induce catalase activity in amphibian tadpoles. 366 17

Oxidants are generated in vivo by multiple mechanisms, including stimulation of leukocytes, hyperoxia, metabolism of arachidonic acid, and the activation of various oxidases. When the biochemical defences to the oxidants are inadequate, injury of tissues results. This injury was observed in rabbits and rhesus monkeys when pulmonary inflammation was induced with phorbol esters or formylated peptide given intrabronchially. We have recently investigated metabolic changes in various cells exposed to oxidants that are generated from stimulated leukocytes, including H2O2, O2, and HOCl. The target cells used were P388D1 murine macrophage-like tumour cells, human peripheral lymphocytes, GM 1380 human fibroblasts and rabbit alveolar macrophages. The oxidants used were H2O2 and PMA stimulated PMNs or neutroplasts. Lysis could only be prevented when catalase was added within the first 30-40 min of H2O2 exposure indicating that early metabolic changes determined the fate of the cell. Within seconds after the addition of H2O2 to P388D1 cells activation of the hexose monophosphate shunt (HMPS) was observed indicative of increased glutathione cycle activity. At the same time DNA strand breaks (determined by an alkaline unwinding technique) were detected. They resulted in the activation of the DNA repair enzyme poly-ADP-ribose polymerase (pADP-RP) within minutes after the addition of H2O2. At the same time ATP and NAD (the substrate of pADP-RP) concentrations dropped and nicotinamide accumulated extracellularly. 10-15 min after oxidant exposure free intracellular Ca++ concentrations determined by Quin 2 fluorescence started to increase due to release from intracellular stores.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxidant and protease injury of the lung. 369 17


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