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

Although oxygen has been known to be toxic for more than 200 years, the clinical importance of oxygen toxicity was not appreciated until an epidemic of retrolental fibroplasia occurred in the early 1950s. Oxygen at high partial pressures is toxic to the respiratory, cardiovascular, nervous, and gastrointestinal systems. Toxicity results from the formation of oxygen-free radicals. These arise within mitochondria as oxygen is reduced to water, as byproducts of prostaglandin and thromboxane synthesis, and by the xanthine oxidase catalyzed reduction of xanthine or hypoxanthine. They are also produced by activated macrophages as part of the immune response. Superoxide anion is the radical most commonly produced. It dismutes to hydrogen peroxide, which is able to diffuse through lipid membranes. Hydrogen peroxide reacts with transition metals to produce the highly reactive hydroxyl radical which can initiate chain reactions of lipid peroxidation leading to cell rupture. Oxygen radical scavengers such as superoxide dismutase and catalase protect the body against normal levels of oxygen-free radicals. Oxygen toxicity can result from either reperfusion of ischemic tissue or prolonged exposure to high concentrations of oxygen. Limiting hyperoxia to maintain arterial oxygen percent saturation (SaO2) greater than or equal to 90% is recommended.
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PMID:Oxygen toxicity: an introduction. 267 91

The importance of respiratory chain activity in the induction of manganese superoxide dismutase biosynthesis was examined in the yeast Saccharomyces cerevisiae by immunological measurement of the level of manganese superoxide dismutase and comparison with copper/zinc superoxide dismutase and two subunits of respiratory chain proteins, cytochrome c1 and core 2, under conditions of growth in which respiratory chain activity was varied. Oxygen consumption by the yeast was also monitored during growth. These comparative studies indicated that under normoxic conditions, glucose repression of the respiratory chain subunits resulted in a parallel repression of the level of manganese superoxide dismutase protein. The increase in the protein levels of manganese superoxide dismutase and core 2 protein under derepressing growth conditions reflected an increase in the level of the mRNA for each protein; thus regulation is, at least in part, at the level of transcription. The following observations support the conclusion that under normoxic conditions manganese superoxide dismutase biosynthesis is primarily regulated by the same means as the respiratory chain components; that is, by glucose (catabolite) repression rather than by oxygen metabolites. 1) When yeast cells were transferred from repressing to derepressing growth conditions in normoxia, manganese superoxide dismutase biosynthesis increased at a rate parallel to that of core 2, and occurred approximately 5 h in advance of increased oxygen consumption by the yeast. 2) When an important site of mitochondrial superoxide radical generation, the cytochrome bc1 complex, was inactivated by deletion of the gene coding for one of its subunits, the level of manganese superoxide dismutase protein was not changed in the mutant compared with the parental strain. However, regulation of manganese superoxide dismutase can be separated from regulation of the respiratory chain proteins in certain instances. During the transition from the logarithmic growth phase to the stationary phase in non-fermentable carbon sources, the level of manganese superoxide dismutase decreased by approximately 50%, whereas the levels of cytochrome c1 and core 2 remained unchanged. Furthermore, yeast grown in hyperoxia of 70-80% oxygen utilizing either repressing or depressing carbon sources, contained significantly higher levels of manganese superoxide dismutase and copper/zinc superoxide dismutase compared to yeast grown in normoxia, whereas the levels of respiratory chain proteins were not affected by hyperoxia.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Regulation of manganese superoxide dismutase in Saccharomyces cerevisiae. The role of respiratory chain activity. 283 36

Lung macrophages (LM) play a crucial role in pulmonary bacterial defense. High inspired oxygen concentrations are used in a variety of diseases and "oxygen toxicity" could impair antibacterial function. We therefore examined the effect of sustained in vitro hyperoxia on LM bactericidal function, and on generation of two bactericidal oxygen metabolites. The LM were cultivated under aerobic (PO2 approximately 140 mmHg) or hyperoxic (PO2 approximately 630 mmHg) conditions for 48 h, and then incubated with Staphylococcus aureus labeled with 3H thymidine for 30 min. Incubated monolayers were processed for measurement of total bacterial uptake and for number of viable intracellular bacteria. Superoxide anion (O2-) and hydrogen peroxide (H2O2) generation was determined in similarly cultivated cells stimulated with opsonized zymosan. The results indicate that the bacterial killing capacity of oxygen-cultivated LM is significantly decreased (p less than 0.001). In addition, a significant (p less than 0.001) decrease in generation of O2- and H2O2 was noted after exposure to high oxygen tensions. The data suggest that decreased bactericidal function after sustained hyperoxia may be due to an impairment of a specific bactericidal mechanism, i.e., an impaired "respiratory burst."
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PMID:Decreased bactericidal function and impaired respiratory burst in lung macrophages after sustained in vitro hyperoxia. 631 Oct 64

Both distal (canine lung strips) and proximal (bovine trachealis strips) airway smooth muscle contract in isolated organ baths as the percentage of environmental oxygen is increased from 12% to 95%. This effect is blocked by prostaglandin synthetase inhibitors (indomethacin, 10(-4)M; meclofenamate, 10(-4)M). To determine whether this contractile response is due to molecular oxygen, or to other products of oxidative metabolism, we examined the effects of ozone, hydrogen peroxide, and superoxide radical generating systems (paraquat and xanthine-xanthine oxidase) on the smooth muscle preparations. Ozone (3 ppm), paraquat (2 mM), and xanthine (10(-3)M)-xanthine oxidase (1 unit) were without effect. Hydrogen peroxide (10(-5)-10(-3)M) produce consistent contractions in both preparations, an effect which was appreciably greater in an hypoxic environment and which was blocked by both indomethacin and meclofenamate. Contraction from both hyperoxia and hydrogen peroxide was partially reversed by various oxygen radical scavengers, including methional (10 mM), ascorbic acid (10 mM), nitroblue tetrazolium (0.3 mM), butylated hydroxyanisole (1 mM), and 2',7' naphthalonediol (1 mM). These results suggest that hyperoxic contraction in airway smooth muscle is mediated by active oxygen species, perhaps by their effects on prostaglandin metabolism.
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PMID:Hydrogen peroxide contracts airway smooth muscle: a possible endogenous mechanism. 733 Apr 88

Aconitase is a member of a family of iron-sulfur-containing (de)hydratases whose activities are modulated in bacteria by superoxide radical (O2-.)-mediated inactivation and iron-dependent reactivation. The inactivation-reactivation of aconitase(s) in cultured mammalian cells was explored since these reactions may impact important and diverse aconitase functions in the cytoplasm and mitochondria. Conditions which increase O2-. production including exposure to the redox-cycling agent phenazine methosulfate (PMS), inhibitors of mitochondrial ubiquinol-cytochrome c oxidoreductase, or hyperoxia inactivated aconitase in mammalian cells. Overproduction of mitochondrial Mn-superoxide dismutase protected aconitase from inactivation by PMS or inhibitors of ubiquinol-cytochrome c oxidoreductase, but not from normobaric hyperoxia. Aconitase activity was reactivated (t1/2 of 12 +/- 3 min) upon removal of PMS. The iron chelator deferoxamine impaired reactivation and increased net inactivation of aconitase by O2-.. The ability of ubiquinol-cytochrome c oxidoreductase-generated O2-. to inactivate aconitase in several cell types correlated with the fraction of the aconitase activity localized in mitochondria. Extracellular O2-. generated with xanthine oxidase did not affect aconitase activity nor did exogenous superoxide dismutase decrease aconitase inactivation by PMS. The results demonstrate a dynamic and cyclical O2-.-mediated inactivation and iron-dependent reactivation of the mammalian [4Fe-4S] aconitases under normal and stress conditions and provide further evidence for the membrane compartmentalization of O2-..
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PMID:Superoxide radical and iron modulate aconitase activity in mammalian cells. 776 42

It is generally known that ischemic reperfusion injury is caused by cell membrane injuries due to superoxide. The present study was carried out to clarify an increase of superoxide production in human neutrophils in state of hypoxia and hyperoxia in vitro. Superoxide of neutrophils was studied at various PO2 values (air, 100% O2, 50% O2, and 100% N2 gas) by chemiluminescence method. The superoxide production (O2-) rates were 84% (air), 84% (100% N2), 87% (100% O2) and 84% (50% O2), respectively. At these stages, PO2 values were 178, 36, 764 and 370 mmHg, respectively. Since superoxide is generated in mitochondria under PO2 of 1 mmHg, it was considered that these different values of PO2 (100% N2, 100% O2 and 50% O2) do not influence the superoxide production. Other factors, such as PAF or cytokine, were speculated to increase superoxide production.
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PMID:[The changes in superoxide anion production in neutrophils on ischemia-reperfusion]. 796 22

Exposure to hyperbaric oxygen [3 atmospheres absolute (ATA) for 45 min] inhibited carbon monoxide (CO)-mediated lipid peroxidation in the brains of rats by preventing the conversion of xanthine dehydrogenase to oxidase, a conversion process known to be due to the action of leukocytes. The effect was the same whether treatment was given 24 hr before or up to 45 min after poisoning. Hyperbaric oxygen did not inhibit the initial interaction of leukocytes with brain microvasculature, based on measurements of myeloperoxidase (MPO) in microvessel segments, but persistent adherence, which is due to B2 integrins, did not occur. Exposing rats to 3 ATA pressure (0.21 ATA O2) after CO poisoning had no significant effects. A progressive reduction in brain microvessel MPO titers occurred with exposure to O2 at 1, 2, or 3 ATA after CO poisoning, but 1 ATA O2 treatment did not significantly inhibit xanthine oxidase formation or lipid peroxidation. In vitro studies with polymorphonuclear leukocytes (PMN) from rats exposed to hyperbaric oxygen corroborated the absence of PMN B2 integrin function, but when these cells were stimulated they exhibited normal B2 integrin expression on their surface and also normal elastase release and superoxide radical production. Adherence functions of PMN that do not require B2 integrins appeared to remain intact after exposure to hyperbaric oxygen, as peritoneal neutrophilia in response to a glycogen challenge was not inhibited. B2 integrin function could be restored by incubating cells with 8 bromo cGMP, and incubation with phorbol ester stimulated the adherence function of both control and hyperbaric oxygen-exposed PMN. These results provide a clear mechanism for the inhibition of CO-mediated brain lipid peroxidation by hyperbaric oxygen and indicate that hyperoxia causes a discrete disturbance of PMN adherence function.
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PMID:Functional inhibition of leukocyte B2 integrins by hyperbaric oxygen in carbon monoxide-mediated brain injury in rats. 824 32

The induction of 8-hydroxyguanine (oh8Gua) endonuclease, a DNA repair enzyme for an oxidatively modified guanine, oh8Gua was studied in various growth conditions in Escherichia coli (AB1157). Anaerobically grown E. coli were found to have a very low activity of this enzyme while aerobically grown cells showed activity about 20 times that of the anaerobic level. Under the same condition, superoxide dismutase (SOD) showed about 6-fold increase in activity. A shift in growth conditions from anaerobic to aerobic resulted in rapid induction of this enzyme, and this induction was blocked (but not completely) by chloramphenicol. It is indicated that molecular oxygen is an effective stimulator to the induction of this enzyme and its induction depends partly on protein synthesis. Superoxide-producing compounds such as paraquat and menadione also increased the activity of endonuclease as well as SOD, but H2O2 showed no effect. Thus, superoxides are also implied as a stimulator. In contrast, hyperoxia induced only SOD not the endonuclease. This induction of the endonuclease by hyperoxia was only observed in a SOD-deficient strain (QC774). The aerobic activity of the endonuclease in QC774 was the same as that of wild types (AB1157, GC4468). It is implied that the responsiveness of oh8Gua endonuclease to superoxides is less sensitive than that of SOD. The endonuclease was also induced by a temperature shift from 30 to 43 degrees C and treatment with nalidixic acid. Among the stimuli used, molecular oxygen seems to be most effective for its induction. The inducible nature of this enzyme will serve as an important mechanism for the protection of oxidative DNA damage in the aerobic environment.
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PMID:Induction of E. coli oh8Gua endonuclease by oxidative stress: its significance in aerobic life. 867 25

Brain reperfusion and/or reoxygenation may be of particular importance in the etiology of neuronal damage after hypoxic-ischemic insult in neonates, especially with reference to the generation of free radicals. To investigate this issue, the influence of either standard reoxygenation or transient hyperoxia was studied on the consequences of severe hypoxia in a model of cultured neurons isolated from the fetal rat brain. Culture dishes were exposed for 6 h to hypoxia (95% N2/5% CO2). They were then placed under normoxia (95% air/5% CO2) or hyperoxia (95% O2/5% CO2) for 3 h, and finally returned to normoxia. Control cultures were kept under normoxic conditions. Cell morphology, protein concentrations, lactate dehydrogenase leakage, energy metabolism, as reflected by specific transport and incorporation of 2-D-[3H]deoxyglucose, as well as superoxide radical formation were analyzed as a function of time. Po2 values in the cell incubating medium were decreased by 78% by hypoxia and increased by 221% by hyperoxia. No morphologic alteration could be noticed before 72 h posthypoxia, when cell degeneration became apparent, with a concomitant reduction in protein contents. Hypoxia-reoxygenation induced a transient cellular hypermetabolism, as shown by a 36% increase in 2-D-[3H]deoxyglucose uptake 24 h after hypoxia, and then a 23% decrease below control values at 72 h. It also led to a sharp increase in the formation of superoxide radicals (+108%). Transient hyperoxia during reoxygenation did not exacerbate these events, and thus would not enhance their deterimental effects on cell integrity.
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PMID:Influence of post-hypoxia reoxygenation conditions on energy metabolism and superoxide production in cultured neurons from the rat forebrain. 884 31

Superoxide formation in pulmonary tissue is modulated by cytokines, PO2, shear force, and disease states, and can be stimulated by drugs. Superoxide has diverse actions on pulmonary cells, including smooth muscle contraction, interaction with redox enzymes, cell proliferation, and gene transcription. In the lungs, there is an impressive array of specific defence mechanisms that destroy superoxide, especially superoxide dismutase (SOD) and metallothionein. Superoxide formation is increased in hyperoxia (e.g., oxygen therapy); however, superoxide-forming enzymes also can be up-regulated in hypoxia. Superoxide has been implicated in acute respiratory distress syndrome, lung ischaemia-reperfusion injury, and lung transplantation. Novel approaches to therapy have been explored, including SOD gene therapy and SOD targeting to the lung. In the future, new drugs interacting with superoxide may provide significant advances in the treatment of lung diseases.
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PMID:Superoxide in the pulmonary circulation. 1066 34


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