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

Pretreatment with the combination of tumor necrosis factor/cachectin (TNF/C) and interleukin 1 (IL-1) increased glucose-6-phosphate dehydrogenase (G6PDH), glutathione reductase (GR), glutathione peroxidase (GPX), catalase (CAT), and superoxide dismutase (SOD) activities in lungs of rats continuously exposed to hyperoxia for 72 h, a time when all untreated rats had already died. Pretreatment with TNF/C and IL-1 also increased, albeit slightly, lung G6PDH and GR activities of rats exposed to hyperoxia for 4 or 16 h. By comparison, no differences occurred in lung antioxidant enzyme activities of TNF/C and IL-1- or saline-pretreated rats exposed to hyperoxia for 36 or 52 h; the latter is a time just before untreated rats began to succumb during exposure to hyperoxia. The results raise the possibility that TNF/C and IL-1 treatment can increase lung antioxidant enzyme activities and that increased lung antioxidant enzymes may contribute to the increased survival of TNF/C and IL-1-pretreated rats in hyperoxia for greater than 72 h.
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PMID:Cytokines increase rat lung antioxidant enzymes during exposure to hyperoxia. 265 81

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 synthesis of Cu,Zn SOD by rat lung increases spontaneously in the fetus in late gestation and during exposure of neonatal and adult rats to greater than 95% O2. To explore the regulation of these increases, we measured rat lung Cu,Zn SOD synthesis and activity. We also cloned and sequenced a rat lung Cu,Zn SOD cDNA that was used to measure Cu,Zn SOD mRNA concentration. We found that (a) under normal gestational and postgestational conditions the synthesis of this enzyme was regulated pretranslationally; (b) the increased synthesis that occurs under hyperoxia (greater than 95% O2), was pretranslationally mediated in otherwise unmanipulated neonatal rats but translationally controlled in hyperoxic adult rats; and (c) in lungs of rats made tolerant to greater than 95% O2 by allowing 24 h rest in air after an initial 48 h in greater than 95% O2, the increased Cu,Zn SOD synthesis that occurred during the second period of hyperoxia was regulated pretranslationally. We conclude Cu,Zn SOD gene expression in the lung is developmentally regulated under normal conditions and in response to an oxidant challenge. Tolerance, whether endogenous or induced, appears to require the accumulation of increased amounts of Cu,Zn SOD mRNA.
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PMID:Rat lung Cu,Zn superoxide dismutase. Isolation and sequence of a full-length cDNA and studies of enzyme induction. 270 31

The effects of hyperoxia and superoxide dismutase (SOD) administration on endothelium-dependent relaxation induced by acetylcholine in isolated rabbit pulmonary artery (PA) preparations were examined. Relaxation responses to papaverine, and contractile responses to KCl and norepinephrine were also assessed using a bioassay technique. Prolonged hyperoxia in rabbits for 3 days produced loss of endothelium-dependent relaxation of the PA, and significant attentuation of contractile response to KCl and relaxation response to papaverine. These changes were prevented by subcutaneous SOD administration. Histological examination using light and electron microscopy revealed focal edema, destruction, and detachment of the PA endothelium in the PA strip preparations from these rabbits. Thus, it is concluded that a high concentration of oxygen exposure in rabbits for 3 days produces not only histological damage in the PA endothelium, but also causes impairment of vascular reactivity to constricting and relaxing agents. Subcutaneous SOD administration prevented oxygen-induced PA damage.
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PMID:Endothelium-dependent relaxation in isolated pulmonary arteries from rabbits exposed to hyperoxia. 278 27

Relative resistance to oxygen toxicity in newborn animals (compared to adults) has been associated with increased antioxidant enzymes and glutathione in lung homogenate. The cell type(s) involved in this increase is unknown. We investigated the effect of hyperoxia in vitro and in vivo on the following antioxidants (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase, and glutathione) in alveolar type II cells from neonatal rats. Type II cells were exposed to 95% oxygen or air for 48 h in vitro. When expressed per microgram DNA, all the antioxidants except catalase increased during in vitro incubation; only glucose-6-phosphate dehydrogenase and glutathione increased when expressed per mg protein. None of the antioxidants was higher in oxygen-exposed cells than in air-exposed cells. Neonatal rats were exposed to 100% oxygen or air in vivo for 4 d before determination of antioxidants in lung homogenate supernatant and alveolar type II cells. Catalase, glutathione peroxidase, and glutathione reductase were higher but glucose-6-phosphate dehydrogenase and glutathione were lower in type II cells than in lung homogenate from control animals. Alveolar type II cell glucose-6-phosphate dehydrogenase and glutathione were increased but catalase and glutathione reductase were decreased by exposure to hyperoxia. We conclude that the oxygen-induced increase in whole lung antioxidants is not explained by alveolar type II cell hypertrophy or increased antioxidants within type II cells during hyperoxia.
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PMID:Effect of hyperoxia on antioxidants in neonatal rat type II cells in vitro and in vivo. 281 89

When the herbicide paraquat (1,1'-dimethyl-4,4'-bipyridylium) was administered to adult rat pulmonary alveolar macrophages (PAM) in primary culture, both a time-dependent and a dose-dependent cytotoxic response (cell death) was observed. An LD50 value of 1 mM was calculated when these cells were exposed to paraquat in vitro for 12 h in Ham's F12 culture medium at 30 degrees C. Cell death was accompanied by the formation of TBA-reactive substances (lipid peroxidation) and was potentiated by hyperoxia (95% O2). In a 95% O2-5% CO2 atmosphere, an LD50 value of 0.1 mM was calculated. In addition, the presence of superoxide dismutase in the culture medium (1700 units/ml) inhibited the cytotoxic response. Since [14C]paraquat was not absorbed into these cells, extracellular superoxide anion radical formation was investigated as the cause of the observed cell death. Paraquat (0.5 mM) was found to stimulate extracellular O-2 generation, from PAM, but only in nonactivated cells. A sevenfold enhancement over the resting rate of radical generation was observed in the presence of paraquat. No increase in the O-2 generation rate of activated macrophages was observed upon the addition of paraquat to the culture medium. These data indicate that paraquat is cytotoxic to the pulmonary alveolar macrophage and further suggest that this cytotoxicity is mediated, at least in part, by an excess, extracellular production of active oxygen species. Implications of these findings with respect to the currently accepted hypothesis of paraquat poisoning in vivo are discussed.
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PMID:Paraquat toxicity in vitro. I. Pulmonary alveolar macrophages. 299 34

The activity of antioxidant enzymes were measured in alveolar type II cells isolated from control and 85% oxygen-exposed rats to determine if type II cells, an oxygen-resistant lung cell type had constitutively high enzyme activities and to measure the effect of hyperoxia on these antioxidant enzyme. Type II cells were isolated from lungs of control rats and rats exposed to 85% O2 for 7 days. In whole lungs of rats exposed to 85% oxygen there is an increase in activity (per lung or per mg lung DNA) in the antioxidant enzymes CuZn superoxide dismutase, Mn superoxide dismutase, catalase, glutathione peroxidase and glucose-6-phosphate dehydrogenase. Oxygen exposure significantly increased (p less than 0.05) all type II cell antioxidant enzyme activities when expressed per mg DNA. The protein content of oxygen exposed type II cells increased 25% from (63.9 +/- 4.8 micrograms/10(6) cells to 79.6 +/- 4.2 micrograms/10(6) cells, p less than 0.05). When type II cell enzyme activities were expressed in U/mg cell protein, only CuZn superoxide dismutase and Mn superoxide dismutase increased in activity following oxygen exposure (by 43% and 28% relative to air exposed lung type II cells, respectively, p less than 0.05). This suggested that most lung cell antioxidant enzymes increased in activity following oxidant stress in proportion to increased cell mass. CuZn and Mn superoxide dismutase increased activity to an extent greater than the increase in type II cell protein content after oxygen exposure. Alveolar macrophages lavaged from control and oxygen-exposed rats were also evaluated, and they had no significant change in CuZn and Mn superoxide dismutase activities. Type II cells accounted for 10% and 17% of alveolar cells in control and oxygen treated rats. By knowing the antioxidant enzyme activities in type II cells, the total enzyme activity of whole lung and the number of type II cells in control and oxygen exposed rats from morphometric data, we calculated the percent of whole lung enzyme activity accounted for by type II cells. Type II cells accounted for a high percentage of lung glucose-6-phosphate dehydrogenase (58% in control rats, 65% in oxygen exposed rats) but a low percentage of Mn superoxide dismutase (4% in control rats, 6% in oxygen exposed rats).
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PMID:Antioxidant enzyme activity in alveolar type II cells after exposure of rats to hyperoxia. 300 82

Experiments were designed to determine the effects of oxygen-derived free radicals on the production and biological activity of endothelium-derived relaxing factor or factors released by acetylcholine. Rings of canine coronary arteries without endothelium (bioassay rings) were superfused with solution passing through a canine femoral artery with endothelium. Superoxide dismutase caused maximal relaxation of the bioassay ring when infused upstream, but not downstream, of the femoral artery; this effect of superoxide dismutase was inhibited by catalase. Infusion of acetylcholine relaxed the bioassay rings because it released a labile relaxing factor (or factors) from the endothelium. When infused below the femoral artery, superoxide dismutase and, to a lesser extent, catalase augmented the relaxations to acetylcholine. Superoxide dismutase, but not catalase, doubled the half-life of the endothelium-derived relaxing factor(s). This protective effect of the enzyme was augmented fivefold by lowering the oxygen content of the perfusate from 95 to 10%. These data demonstrate that: superoxide anions inactivate the relaxing factor(s) released by acetylcholine from endothelial cells and hyperoxia favors the inactivation of endothelium-derived relaxing factor(s).
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PMID:Superoxide anions and hyperoxia inactivate endothelium-derived relaxing factor. 301 Jul 44

The failure of adult rats to survive prolonged exposure to greater than 95% O2 is generally ascribed to the inability of their lungs to increase antioxidant enzyme synthesis in response to the oxidant challenge. We studied the synthesis rate of the antioxidant enzyme CuZn superoxide dismutase (CuZn SOD) in lungs of adult and neonatal rats exposed to conditions that alter the lung's oxidant-to-antioxidant balance. Lung CuZn SOD synthesis in the adult was significantly increased after 24 h of hyperoxia but fell to control levels after further exposure, whereas in neonatal lungs an increased rate of synthesis of CuZn SOD was found only after 72 h of hyperoxia. The adult lung responded to two in vitro oxidant stresses, [diethyldithiocarbamate exposure and heat (42 degrees C)] with increases in CuZn SOD synthesis twice the magnitude of those in the neonatal lung. These data indicate that the adult lung is at least as capable as the neonatal lung of increasing its synthesis of CuZn SOD in response to an oxidative stress. However, the inability of the adult lung to maintain an increased rate of CuZn SOD synthesis during in vivo hyperoxia may contribute to the poor tolerance of the adult lung to greater than 95% O2.
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PMID:Differences in CuZn superoxide dismutase induction in lungs of neonatal and adult rats. 303 15

Preexposure of rats to sublethal levels of hyperoxia or ozone reduces morbidity and mortality when the animals are subsequently exposed to lethal levels of either oxidant stress. Lung homogenates and isolated type II pneumocytes from rats exposed to these oxidant stresses demonstrate enhanced antioxidant enzyme activities. Antioxidant enzymes, superoxide dismutase, catalase, and glutathione peroxidase are responsible for the detoxification of partially reduced oxygen species, superoxide and hydrogen peroxide, to less reactive states. Potential pulmonary cellular loci of partially reduced oxygen include mitochondrial NADH dehydrogenase, endoplasmic reticulum-derived NADPH cytochrome c reductase, and cytosolic xanthine oxido reductase. Thus partially reduced oxygen species are hypothesized to mediate hyperoxia and ozone-induced pulmonary damage. This damage may be attenuated by enhanced intracellular antioxidant enzyme activities. Pharmacologic augmentation of pulmonary antioxidant enzymes may be accomplished via intratracheal or intravascular delivery of liposomes containing antioxidant enzymes. Rats pretreated with liposomes containing both superoxide dismutase and catalase, when subsequently exposed to lethal levels of hyperoxia, demonstrate enhanced survival compared with control animals or with animals treated with control liposomes or native antioxidant enzymes. Finally, knowledge obtained from in vitro investigations optimizing liposomal delivery to specific pulmonary cell types may further aid in reducing in vivo pulmonary damage to hyperoxia and ozone.
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PMID:Pulmonary metabolism of reactive oxygen species. 306 93


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