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

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

The active oxygen species generated by ionizing radiation, hyperoxia, paraquat and hydrogen peroxide induced unscheduled DNA synthesis and DNA synthesis rate inhibition in human fetal lung fibroblast (IMR-90) and transformed cell line derived from Syrian hamster embryo fibroblast (BP6T). The D-glucose and sucrose, which were unable to generate active oxygen species, could induce neither unscheduled DNA synthesis nor DNA synthesis rate inhibition. The indicator of DNA synthesis rate inhibition for active oxygen species was more sensitive than that of unscheduled DNA synthesis. All the enhancing chemicals on active oxygen species aggravated DNA damage, while all the inhibiting chemicals alleviated DNA damage. Results showed that active oxygen species do damage DNA. The active oxygen species mechanism for carcinogenesis, mutation and aging is applicable.
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PMID:DNA damage induced in mammalian cells by active oxygen species. 285 Nov 68

Background levels of chromosomal aberrations and sister-chromatid exchanges (SCEs) were determined in CHO-99 cells, an oxygen-tolerant variant substrain of Chinese hamster ovary (CHO-20) cells capable of stable proliferation under an atmosphere of 99% O2/1% CO2, a level of hyperoxia at which cultured mammalian cells normally cannot survive. The mean chromosomal aberration frequency in CHO-99 cells was as high as 1 aberration per cell (mainly chromatid and chromosome gaps and breaks) versus 0.05 aberration/cell in CHO-20 cells, while the SCE frequency was 1.7- to 2.1-fold increased. While most aberrations were apparently distributed at random over the chromosomes, up to 31% of the aberrations appeared to be involved in site-specific fragility at a homologous site in chromosomes Z3 and Z4. Immediately upon shifting CHO-99 cells to air-equilibrated conditions their SCE frequency decreased to the control level, whereas the aberration rate persisted at a still elevated level of 0.16-0.31 aberration per cell, even after a culture period of 14 weeks under normoxia. This indicates that at least part of the chromosomal instability is a constitutional property of the variant cells, i.e., not directly dependent upon hyperoxic stress. In CHO-99 X CHO-20 hybrids the occurrence of chromatid-type aberrations and fragile site but not that of chromosome-type aberrations was suppressed under normoxic conditions, suggesting that chromatid-type aberrations and fragile site expression on the one hand and chromosome-type aberrations on the other hand are mediated by different constitutional defects in CHO-99 cells. No gross alterations in (deoxy)ribonucleoside triphosphate pools were detected in CHO-99 cells that could be held responsible for their chromosomal instability. In addition, no increased level of DNA damage was detected by the technique of alkaline elution. The excessive chromosomal instability in CHO-99 cells, as observed under hyperoxic conditions, may originate from reactive intermediates giving rise to DNA double-strand breaks and/or a type of DNA lesion that is resistant to the conditions of the alkaline elution technique. However, alternative mechanisms based upon reactive species interfering with DNA replication/repair processes cannot be excluded.
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PMID:Chromosomal instability in an oxygen-tolerant variant of Chinese hamster ovary cells. 291 Dec 68

Adaptation to hyperoxia has been attributed to increased activities of protective enzymes, but we suggest that an additional factor may be the lung's capacity to repair itself in hyperoxia. Such repair would require increased polyamines, but there are reports that two key enzymes of polyamine metabolism are suppressed by hyperoxia or oxidants. Because rats can adapt to hyperoxia but mice cannot, we compared their changes of polyamine metabolism and judged cell repair by using [3H]thymidine to estimate DNA synthesis. Both species developed increased ornithine decarboxylase activity and putrescine content, but the mouse did not develop increased S-adenosylmethionine decarboxylase activities or increases of spermidine and spermine as did the rat when exposed to 85% O2. Furthermore, we confirmed that the rat lung does respond to hyperoxia with increased DNA synthesis, but the mouse lung does not. The results suggest that in addition to increased activities of protective enzymes, increased repair processes in the rat lung may play a role in its capacity to adapt to hyperoxia. The incomplete response of polyamine metabolism in mice may contribute to their inability to adapt in hyperoxia.
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PMID:Polyamines, DNA synthesis, and tolerance to hyperoxia of mice and rats. 291 88

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

Adult BALB/c mice, which are sensitive to hyperoxia (LT50 = 4.5 days 100% O2), were made tolerant to 100% O2 after treatment with butylated hydroxytoluene (BHT). Following a single ip dose of 400 mg/kg, mice survived longer periods in O2 when exposed to O2 at 7, 14, and 21, but not 2 days, following BHT injection. The tolerance was most pronounced on Day 7 (LT50 = 9.6 days) and decreased with time (LT50 7.7 days on Day 14 and 7.3 days on Day 21). Glucose-6-phosphate dehydrogenase levels of whole lung homogenates following BHT exposure were elevated on Day 7 when expressed as per milligram of protein or DNA. Other antioxidant defenses were generally increased only when expressed on a per lung basis. Histopathology of lungs from BHT-treated mice revealed typical BHT-induced lung lesions. BHT treatment followed by long-term hyperoxic exposure produced additional damage to the lung manifested by the exudative phase of diffuse alveolar damage with 1 week of exposure. This was followed by the proliferative phase, then chronic interstitial pneumonitis and fibrosis with 2 and 6 weeks of exposure, respectively. Mice continued to survive in 100% O2 despite this damage. We conclude that pretreatment with BHT enhances O2 tolerance in mice, which may be mediated by induction of antioxidant defenses and also by cell renewal induced by BHT damage.
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PMID:Oxygen tolerance in mice following exposure to butylated hydroxytoluene. 318 20

Explants of mouse lung were cultured at various stages of injury after exposure to hyperoxia for determination of whether endothelial or epithelial injury alone could stimulate fibrosis in a blood-free environment. Mice were exposed to 95% O2 for periods up to 6 days. Then one lobe of lung was prepared for organ culture, and others were used for assessment of lung damage by morphologic studies and by the protein and cellular content of bronchoalveolar lavage (BAL) fluid. Explants cultured when the lung showed endothelial injury only were not different from air-exposed controls. As alveolar damage, particularly to Type 1 epithelial cells, increased at 6 days, more protein was found by lavage; and after culture, overall DNA synthesis in explants was reduced. Autoradiography showed that epithelial cell proliferation was preferentially retarded while fibroblast growth became predominant. Collagen production was also significantly increased after 3 and 6 days of culture. In these explants there were few macrophages and no white blood cells or other blood components. Some mice, returned to air after hyperoxia, showed prompt epithelial repair, and cultures of these lungs were not different from controls. The results suggest that severe injury and retarded repair of the alveolar epithelium disturbs normal epithelial-fibroblast interactions and is sufficient to promote the fibrotic process. Less severe injury involving the endothelium only is not associated with fibrosis.
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PMID:Relationship of alveolar epithelial injury and repair to the induction of pulmonary fibrosis. 334 52

We fed Sprague-Dawley rats either freely or by restricting them to 20% of their usual diet for 21 days. In one experiment, we refed half of the food-restricted rats for 12 h, then exposed the three groups to air or 85% O2 for 5 days. The mortalities in 85% O2 were 100, 33, and 0% for the food-restricted, restricted-refed, and freely fed groups, respectively. In air lung polyamine contents and glucose 6-phosphate dehydrogenase and NADP-dependent isocitrate dehydrogenase activities were significantly lower with food restriction. After hyperoxia, lung polyamine and protein contents and enzyme activities were increased in the two surviving groups, but spermine and DNA contents of refed rats did not increase. In a second experiment, we exposed rats to 60% O2 and found that DNA synthesis of food-restricted rats was lower than the freely fed rats in air and remained low after hyperoxia. We conclude that food restriction increases the mortality from 85% O2 and is associated with lower DNA synthesis and polyamine content. We speculate that food-restricted animals may accumulate greater lung injury partly because of a compromised repair process.
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PMID:Effects of food restriction and hyperoxia on rat survival and lung polyamine metabolism. 339 99

The consequences of maternal hypoxia and hyperoxia on maternal and fetal lung growth and in particular on the relationship between the three gas exchange organs (lungs and placenta) were studied in albino rats. Pregnant rats were exposed to one of the following: (1) 10% O2 in N2 or 100% O2 for 2 days beginning at day 7, 11, 14, or 18 of pregnancy; (2) 10% O2 in N2 or 100% O2 for 10 h/day beginning at day 7; or (3) 14-11% O2 in N2 continuously beginning at day 14 till day 21 when they were sacrificed. Maternal lung growth was assessed by measuring the lung weight, lung air volume and lung DNA content, and the fetal lung growth by lung DNA content. Hypoxia and hyperoxia of short duration (2 days) had no significant effect on maternal and fetal lungs and placenta. The major findings with intermittent hypoxia and hyperoxia, and with 1 week continuous hypoxia were as follows: (1) hypoxia initiated enlargement in maternal lung, liver, kidney and heart, and growth retardation in the fetus; (2) the direct relationships which exist in normal pregnancy between placental weight or DNA content and fetal body weight were abolished by maternal hypoxia, and that which exists between maternal and fetal lung DNA content, by hypoxia and hyperoxia; (3) both hypoxia and hyperoxia, applied at early pregnancy, caused small for body weight placenta and lung; and (4) neither maternal hypoxia nor hyperoxia influenced fetal lung maturation. It is speculated that reduction in fetal lung DNA content with maternal hypoxia may result from the direct and indirect effects of hypoxia on fetal lung, namely inhibition of cell multiplication and reduced pulmonary blood flow; and that a small fetal lung with maternal exposure to 100% O2, may result from redistribution of blood flow and nutrient supplies to fetal organs with lungs receiving a smaller proportion of it.
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PMID:Fetal lung growth: influence of maternal hypoxia and hyperoxia in rats. 342 Mar 24

To determine the respective role of thymidine kinase and thymidylate synthase activities in the hyperoxia-induced decrease in DNA synthesis and their relationship with cell replication, we measured these two enzyme activities in primary cultures of porcine aortic endothelial cells under different O2 concentrations for various durations. In confluent cells, exposure to 95% O2 for 5 days reduced thymidine kinase activity to 15% of control values; thymidylate synthase activity was unaffected. In preconfluent cells exposed to 95% O2 for 2 days, similar results were obtained, together with evidence for arrest in cell proliferation. Thymidylate synthase activity could therefore not be related to decreased cell proliferation under hyperoxia. [3H]thymidine incorporation into DNA, thymidine kinase activity, and cell proliferation were all similarly affected under exposure to graded O2 concentration for 2 days. Thymidine kinase appears to be a key enzyme in the modulation of DNA synthesis from thymidine and in its replication in endothelial cells.
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PMID:Thymidine kinase, thymidylate synthase, and endothelial cell growth under hyperoxia. 355 73


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