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

Corticosteroids affect type II alveolar epithelial cells, increase the lung's content of lipids associated with pulmonary surfactant, and have been used to treat the adult respiratory distress syndrome. We used hyperoxia to produce diffuse alveolar damage in rats and then determined the contents of lung lipids and the incorporation of precursors into these lipids while the rats recovered in air and received either hydrocortisone or saline injections. With saline injections (control) the total lipid content after hyperoxia and 48 hours recovery in air was nearly twice the lipid content of lungs never exposed to hyperoxia; many lipids, including phosphatidylcholine (PC), shared in this increase. With hydrocortisone injections the total lipid content, when expressed per lung, was not significantly greater than with saline injections but when expressed per mg DNA several lipid subgroups, including phosphatidylcholine, were significantly greater. Palmitate incorporation into most lipids of lung slices was not significantly different by 48 hours of recovery, and hydrocortisone had a modest effect after 96 hours. In contrast to the incorporation of palmitate, the incorporation of glycerol and of lysophosphatidylcholine (LPC) nearly doubled in most lipids during the recovery phase. Hydrocortisone injections were associated with greater glycerol incorporation after 96 hours of recovery in nearly all lipids and LPC incorporation was increased primarily into PC. We conclude that lung lipids increase markedly during recovery from severe oxygen toxicity and that hydrocortisone leads to additional increases of saturated and unsaturated PC.
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PMID:Lung phospholipids during recovery from oxygen toxicity are altered by hydrocortisone. 356 66

This brief illustration of the effects of O2 metabolites and of hyperoxia on some of the main functions of the cells, DNA and protein synthesis, indicates that major changes can occur in cells exposed to oxidative stresses such as those occurring in an inflammatory reaction. The relative sensitivity of the various cell populations may favor the emergence of some cells and the disappearance of others. Depending on the sensitivity of different enzymes to oxidative injury, the response of cells in terms of both mediator production and of response to the action of the mediators themselves may be affected.
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PMID:Effects of oxygen intermediates on cellular functions. 359 16

The potential protective effect of N-acetylcysteine against various types of oxidative stress (exposure to hyperoxia, treatment with paraquat, incubation in the presence of the hypoxanthine-xanthine oxidase system) was tested in primary cultures of porcine aortic endothelial cells. It was compared to that of selenomethionine (Se-Met), known to increase glutathione peroxidase activity, when given either alone or in combination with N-acetylcysteine. LDH release, 3H-thymidine (TdR) incorporation into DNA and DNA content were measured to assess the cytotoxic effect of the conditions tested. Total and oxidized glutathione content was also determined. Whereas Se-Met had a partial protective effect on all the conditions but paraquat treatment, N-acetylcysteine administration had no effect on the hyperoxia induced changes and significantly worsened the cytotoxic action of paraquat. On the other hand, LDH release following an incubation in the presence of the hypoxanthine-xanthine oxidase was significantly reduced after N-acetylcysteine treatment. No major change in total nor in oxidized glutathione followed N-acetylcysteine treatment in control and experimental conditions. A dose-dependent protective effect of N-acetylcysteine was obtained when this agent was given concomitantly with the xanthine oxidase system. These data suggest that in cultured endothelial cells a N-acetylcysteine-related protective effect, if present, is most likely to result from the direct scavenging action of N-acetylcysteine.
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PMID:Comparative study on the selenium- and N-acetylcysteine-related effects on the toxic action of hyperoxia, paraquat and the enzyme reaction hypoxanthine-xanthine oxidase in cultured endothelial cells. 368 96

Adult rats exposed to hyperoxia are protected from lung injury by treatment with bacterial endotoxin. Experiments were undertaken to determine whether endotoxin treatment produces a mitogenic effect on the lung. Endotoxin treatment caused a significant (P less than .05) loss of body weight (8%) in rats exposed to either air or greater than 95% O2 for 24 hr. Therefore, experiments were also undertaken in which both saline- and endotoxin-treated rats were starved for the duration of the experiments to make equal any nutritional imbalance. The rate of DNA synthesis in lung slices from fed rats treated with endotoxin did not differ from that of saline-treated controls. In contrast, lung DNA synthesis in starved rats treated with endotoxin increased 50%. The effect of endotoxin treatment was similar in rats breathing air or greater than 95% O2, and lung protein synthesis generally paralleled lung DNA synthesis. These results indicate that endotoxin does exert a mitogenic effect on the lung and this effect can be masked by the nutritional imbalance resulting from endotoxin administration.
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PMID:Mitogenic response of rat lung to endotoxin exposure. 368 25

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

The effects of hyperoxia on lung tumor development were examined in mice and rats. In mice, exposure to 70% O2 prevented the development of urethan- or 3-methylcholanthrene-induced lung tumors. Dietary antioxidants [butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA)] were unable to prevent the inhibition of tumor development by oxygen, although BHT retained its capability to enhance tumor development in mouse lung. In visible-size tumors, oxygen did not depress DNA synthesis. Oxygen also reduced the number of pulmonary metastatic nodules after i.v. injection of mammary gland-derived carcinoma cells, but failed to inhibit growth of murine lung carcinoma or murine melanoma-derived cell lines. Rats treated with one single intratracheal instillation of 3-methylcholanthrene developed multiple lung lesions; their growth could be prevented by exposure of the animals to 40 or 70% O2. It is concluded that hyperoxia prevents development of transformed cells in vivo in the lung and may affect adversely the growth of selected cell lines metastatic to the lung.
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PMID:Modification of lung tumor growth by hyperoxia. 374 30

Treatment of rats with endotoxin, as late as 24 h after beginning exposure to greater than 95 O2 at 1 atm, increases survival at 72 h from 20-30% to greater than 95% (J. Clin. Invest. 65: 1104, 1980), whereas treatment with corticosteroids reduces survival (Toxicol. Appl. Pharmacol. 47: 367, 1979). Since endotoxin is mitogenic to some cells and glucocorticosteroids decrease DNA synthesis by lung cells, we asked 1) is endotoxin mitogenic to the lung, and, if so, 2) is the mitogenic effect required for endotoxin to produce tolerance to hyperoxia? We found endotoxin administered in vivo does have a mitogenic effect on the lung as indicated by an increased rate of DNA synthesis by lung slices; dexamethasone blocked this effect. However, although dexamethasone given alone markedly diminished survival in hyperoxia, dexamethasone did not impair the protection conferred to rats by endotoxin against the edemogenicity and lethality of hyperoxia. Furthermore, dexamethasone did not diminish the rise of antioxidant enzyme activity in the lungs of endotoxin-treated O2-exposed rats. We conclude endotoxin can produce tolerance to hyperoxia even when its mitogenic action on the lung is substantially diminished.
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PMID:Mitogenic effect of endotoxin on lung and tolerance of rats to hyperoxia. 389 78

Paraquat (PQ) is a herbicide known to generate O2 radicals and to injure lung epithelial cells, leading eventually to pulmonary fibrosis. To test for the possible existence of a direct cytotoxic action of PQ on endothelial cells, we have studied, for up to 5 days, the action of 10(-6) to 10(-4) M PQ on primary cultures of pig aortic endothelial cells and compared these effects to those obtained with exposure to 95% O2-5% CO2. The decrease in DNA and protein content of Petri dishes and the increase in lactate dehydrogenase release were found to depend on PQ concentration and the duration of exposure to PQ. The toxic effects of hyperoxia were intermediate, ranging between those obtained with 10(-5) and 10(-4) M PQ. Hyperoxia and 10(-4) M PQ produced a similar marked inhibition of DNA synthesis after a 1-day period of exposure. Combined exposure to both PQ and hyperoxia resulted in changes comparable to those obtained with hyperoxia alone (decrease in protein and DNA content) or PQ alone (lactate dehydrogenase release). Additive effects were seen only for the inhibition of DNA synthesis. The selenomethionine-related increase in glutathione peroxidase activity had a protective effect against hyperoxia-induced lactate dehydrogenase release but not against PQ induced cytolysis. Finally, shorter exposures to O2 and PQ revealed the existence of a trend toward recovery only for cells exposed to hyperoxia. The prolonged toxic action of PQ could not be related to PQ accumulation and storage by endothelial cells. These studies indicate that PQ can exert a direct, dose-dependent, and prolonged cytotoxic effect on cultured endothelial cells.
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PMID:Direct toxic effects of paraquat and oxygen on cultured endothelial cells. 396 1

An edited summary of an Interdepartmental Conference arranged by the Department of Medicine of the UCLA School of Medicine, Los Angeles. The Director of Conferences is William M. Pardridge, MD, Associate Professor of Medicine.Polyamines, necessary for cell growth, influence many cell functions. As small polyvalent cations they can change the configuration of large polyvalent anions, such as DNA, and alter their sensitivity to other molecules including chemotherapeutic agents. By altering polyamine content in a cell, we can change its growth, its susceptibility to drugs and change other cellular functions. Malignant conditions, other proliferative diseases and infections are the most apparent clinical conditions likely to improve by depleting polyamines and suppressing cell growth. Proliferative disorders of the skin respond to many agents that suppress polyamine metabolism. Hyperoxia may suppress cell growth in the lung by suppressing polyamine metabolism.
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PMID:Polyamines in clinical disorders. 397 21

The effects of exposure to CdCl2 aerosols followed by hyperoxia were studied in mouse lung. Special emphasis was placed on analysis of cell proliferation following injury. Male Balb/c mice were exposed to aerosols of 4.9 micrograms Cd/liter for 1 hr while controls were exposed to water aerosols. Immediately after, half of each group was placed in 80% O2 for 6 days, while the rest were left in room air. Three endpoints were used to assess lung injury; measurement of hydroxyproline, [14C]thymidine incorporation into DNA, and histopathology. Parenchymal and bronchiolar labeling indices were determined following autoradiography. A 1-hr exposure to CdCl2 aerosols caused marked cell proliferation in the lung with the peak of cell labeling occurring at Day 5. In animals exposed to both CdCl2 + 80% O2, the cell labeling peak was delayed until Day 9. Cell differentiation studies showed a delay in the peak of type II epithelial cell and endothelial cell division when CdCl2 exposure was followed by the 80% O2 treatment. On Day 15 most of the labeled cells were identified as interstitial cells in both treated groups. Bronchiolar cell labeling was suppressed at the early time period in the Cd + O2 group. With time, the histologically visible lung lesions tended to resolve in animals exposed to CdCl2 or CdCl2 and 80% O2, whereas total pulmonary hydroxyproline remained at all times (3, 6, and 12 months) significantly higher in Cd-treated animals when compared to controls. It was concluded that acute lung injury by a toxic inhalant can be amplified if there is an initial delay in pulmonary cell proliferation following an acute insult.
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PMID:Cadmium-induced lung injury: cell kinetics and long-term effects. 402 12


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