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

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

L-Arginine is the substrate for synthesis of nitric oxide (NO.) by NO synthase which physiologically produces vasodilation. The reaction of NO. or its metabolites with O2 or its metabolites, however, can produce toxic reactive species which may cause cellular injury. We hypothesized that excessive NO. production in isolated perfused rabbit lungs at elevated PO2 could support the production of toxic nitrogen metabolites. In isolated perfused rabbit lungs ventilated with 95% O2, 1.0 mM L-arginine caused significant pulmonary hypertension and edema. These effects of L-arginine were attenuated by the NO. synthase inhibitor, L-NAME (0.5 mM), not affected by SOD pretreatment (100 u/ml) and reversed by pretreatment with catalase (200 u/ml), suggesting a mechanism involving H2O2. This mechanism was supported by producing L-arginine mediated injury in normoxic lungs in the presence of a H2O2 generating system. This injury also was attenuated by L-NAME. On the basis of these results, we conclude that H2O2 interacts with NO. or one of its oxidized metabolites to contribute to acute lung injury during hyperoxia. Such a mechanism may involve peroxynitrite anion, although direct proof of its formation is lacking under these conditions.
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PMID:L-arginine enhances injury in the isolated rabbit lung during hyperoxia. 754 44

Endothelial cells are critical targets in both hypoxia- and reoxygenation-mediated lung injury. Reactive O2 species (ROS) have been implicated in the pathogenesis of hypoxic and reoxygenation lung injury, and xanthine dehydrogenase/oxidase (XDH/XO) is a major generator of the ROS. Porcine pulmonary artery endothelial cells (PAEC) have no detectable XDH/XO. This study was undertaken to examine 1) ROS production by hypoxic porcine PAEC and their mitochondria and 2) ROS production and injury in reoxygenated PAEC lacking XDH/XO activity. Intracellular H2O2 generation and extracellular H2O2 and O2 divided release were measured after exposure to normoxia (room air-5% CO2), hypoxia (0% O2-95% N-5% CO2), or hypoxia followed by normoxia or hyperoxia (95% O2-5% CO2). Exposure to hypoxia results in significant reductions in intracellular H2O2 formation and extracellular release of H2O2 and O2 by PAEC and mitochondria. The reductions occur with as little as a 2 h exposure and progress with continued exposure. During reoxygenation, cytotoxicity was not observed, and the production of ROS by PAEC and their mitochondria never exceeded levels observed in normoxic cells. The absence of XDH/XO may prevent porcine PAEC from developing injury and increased ROS production during reoxygenation.
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PMID:Effect of hypoxia and reoxygenation on the formation and release of reactive oxygen species by porcine pulmonary artery endothelial cells. 762 87

Hyperoxia induces the expression of the hemopexin (Hx) gene in the liver in vivo. To investigate whether the Hx gene is activated by oxygen as such or via H2O2 as an oxygen signal transmitter the effects of arterial and venous O2 tensions as well as different concentrations of H2O2 on Hx mRNA expression were studied. After preculturing primary rat hepatocytes for 24 h at arterial O2 (16%) Hx mRNA was expressed with a maximal level (= 100%), when arterial O2 tension proceeded for 2 h, and to values of approximately 50%, when venous O2 tension (8%) proceeded for 2 h. When hepatocytes were precultured for 24 h under venous O2, Hx mRNA was induced by arterial O2 to values of 60% and under venous O2 to values of approximately 35%. The expression of beta-actin remained unchanged under arterial and venous O2. Exposure of hepatocyte cultures to H2O2 decreased the expression of Hx mRNA in a dose-dependent manner after 2 h, while heme oxygenase-1 (HO-1) mRNA was induced 2.5 fold. The results suggest that O2 per se rather than the reactive oxygen intermediate H2O2 modulates Hx expression.
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PMID:Modulation of hemopexin gene expression by physiological oxygen tensions in primary rat hepatocyte cultures. 764 92

The effect of aging on the ability of Caenorhabditis elegans to adapt to oxidative stress was examined. Oxidative stress was applied with the quinone plumbagin or with hyperoxia, both of which are expected to increase intraorganismal production of O2.- and of H2O2. Young nematodes adapted by increasing their content of superoxide dismutase (SOD) and they survived, whereas older nematodes did not induce superoxide dismutase and suffered loss of viability. It thus appears that, in C. elegans, loss of adaptability to oxidative stress, monitored in terms of induction of SOD, is a hallmark of senescence.
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PMID:Adaptation to oxidative stress in young, but not in mature or old, Caenorhabditis elegans. 774 2

The significance of manganese superoxide dismutase (MnSOD) induction in cells and tissues during oxidant stress is still poorly understood. In this study, transformed human bronchial epithelial cells (BEAS 2B) were treated with interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), or with combination of these cytokines (10 ng/ml concentrations) for 48 or 72 h and exposed to selected oxidants. TNF-alpha and IFN-gamma + TNF-alpha combination resulted in a marked increase of MnSOD protein and MnSOD activity. When cells pretreated with the cytokines were exposed to hyperoxia (95% O2, 72 h), menadione (5-50 microM, 4 h), or H2O2 (0.5 and 5 mM, 4 h), in all cases IFN-gamma and TNF-alpha enhanced oxidant-related cell injury. The effect was most significant with cells pretreated with a combination of IFN-gamma and TNF-alpha. Antioxidant enzymes such as total SOD, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase did not change significantly during the cytokine treatment. Catalase activity was not changed by IFN-gamma or TNF-alpha but it decreased significantly (34%) in IFN-gamma + TNF-alpha-treated cells. Free radical generation was not changed by these cytokines in acute (30 min) experimental conditions or after 48-h treatment. These results suggest that cytokine-induced MnSOD does not protect bronchial epithelial cells against endogenously or exogenously generated oxidants in vitro. In fact, cells that contained the highest MnSOD activity were the most sensitive to subsequent oxidant damage.
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PMID:Mitochondrial superoxide dismutase induction does not protect epithelial cells during oxidant exposure in vitro. 784 Feb 31

Proteins that decrease the surface activity of surfactant accumulate in epithelial lining fluid in respiratory failure. The aim of this study was to isolate a surfactant inhibitor from the airways of rabbits in acute respiratory failure induced by bronchoalveolar lavage (BAL). This inhibitor was identified as being transferrin (TF). Unlike serum TF, TF recovered in respiratory failure was saturated with iron (Fe(3+)-TF). Fe(3+)-TF decreased the surface activity of normal surfactant in vitro, whereas iron-free TF had no effect. In the presence of H2O2 and a reducing agent, Fe(+3)-TF inactivated the surfactant complex: the surface absorption rate was decreased, immunoreactive surfactant protein A was decreased, and malondialdehyde was formed. The acute effects of Fe(3+)-TF and iron-free TF applied to the airways were studied in animal models. In respiratory failure induced by BAL, Fe(3+)-TF deteriorated respiratory failure, whereas iron-free TF had no effect. In respiratory failure induced by hyperoxia for 48 h, administration of iron-free TF ameliorated the respiratory failure and improved the surface activity in BAL. We propose that Fe(3+)-TF accumulating in epithelial lining fluid during lung damage contributes to surfactant inhibition and promotes the formation of free radicals that inactivate the surfactant system.
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PMID:Interaction of transferrin saturated with iron with lung surfactant in respiratory failure. 800 25

Exposure of the lung to elevated oxygen leads to structural and cellular injury followed by extensive tissue remodeling. In vitro models utilizing isolated cells exposed to hyperoxic conditions or exogenously added oxidants may be injurious or stimulatory depending on the specific cell type and level and duration of exposure. In the present study, proliferation of cultured rat tracheal smooth muscle cells was inhibited by oxygen concentrations of 40 and 70% compared with a "normoxic" concentration of 21%. Exposure to 70% oxygen had a hypertrophic effect on the cells, as indicated by increased cellular protein content, whereas cells exposed to 21% oxygen did not show increased protein content. Exogenously added oxidant, H2O2, resulted in complete inhibition of growth of tracheal smooth muscle cells at concentrations > 3 microM. Much higher concentrations of H2O2 were required to inhibit proliferation of vascular smooth muscle cells and rat lung fibroblasts. The heightened sensitivity of airway smooth muscle cells to oxygen and oxidants may be an important factor in the early events following hyperoxia-induced lung injury.
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PMID:Hyperoxia inhibits proliferation of cultured rat tracheal smooth muscle cells. 807 31

We have investigated factors that regulate hydrogen peroxide (H2O2) release from vascular endothelial cells. Endothelial cells produce H2O2 at an intracellular site in the vicinity of peroxisomes and at a second site near the cell surface that is inaccessible to intracellular catalase or glutathione peroxidase. Regulation of H2O2 generation at the intracellular site was studied using aminotriazole, which inactivates catalase in the presence of H2O2. Regulation of H2O2 generation at the second site was studied by measuring H2O2 release into the medium. The rate of H2O2 release was constant over 2 h when cells were incubated in room air. Changing O2 levels in the atmosphere from 0% to 10% O2 resulted in a threefold increase in the rate of H2O2 release. Elevation of O2 levels from 10% to 95% O2 produced no further enhancement in the rate of release. Preincubation of cells under hypoxic conditions did not lead to an exaggerated rate of H2O2 release when cells were returned to room air. Pretreatment of cells with exogenous H2O2 inhibited subsequent H2O2 release while pretreatment with catalase enhanced H2O2 release. Although arachidonic acid transiently enhanced the rate of H2O2 release through a mechanism dependent on PGH synthase, basal H2O2 release was independent of this enzyme. Neither hypoxia, hyperoxia, or hypoxia followed by reoxygenation altered H2O2 generation at the intracellular site accessible to peroxisomal catalase. These data demonstrate that H2O2 release from endothelial cells is responsive to changes in O2 concentrations over a narrow range. The mechanisms involved are subject to product inhibition and appear to be saturated at 10% O2 in the atmosphere.
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PMID:Modulation of hydrogen peroxide release from vascular endothelial cells by oxygen. 825 92

NAD(P)H:quinone reductase, or DT-diaphorase, has been studied primarily in the liver where it appears to function as an antioxidant-like enzyme in the 2-electron reduction of some quinones to less toxic hydroquinones. This property together with new molecular biology evidence that oxidants such as H2O2 can induce gene transcription of DT-diaphorase provide especially intriguing reasons to examine the possibility that lung DT-diaphorase could have an important antioxidant enzyme role versus pulmonary O2 toxicity during exposure to hyperoxia. We found that similar to the 'classical' lung antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) DT-diaphorase activity increased significantly in the late gestational fetal lung; also its activity was altered in the same way as the antioxidant enzymes by prenatal hormonal treatment. Another similarity is that DT-diaphorase activity was induced in the neonatal animal lung during hyperoxia, but not in the adult animal lung. However, using various drug treatments which markedly increased lung DT-diaphorase activity (e.g., 3-methylcholanthrene, butylated hydroxyanisole, methimazole) we found no improved hyperoxic survival in the treated adult rats. Also, dicumarol treatment, which markedly depressed DT-diaphorase activity, did not diminish the hyperoxic survival rate in an O2-tolerant adult rat model. Thus, we conclude that unlike the classical antioxidant enzymes, increased pulmonary DT-diaphorase activity is probably neither necessary nor sufficient to protect against pulmonary O2 toxicity during hyperoxia.
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PMID:Does lung NAD(P)H:quinone reductase (DT-diaphorase) play an antioxidant enzyme role in protection from hyperoxia? 846 17


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