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

Neonatal rats usually lose their marked tolerance to hyperoxia at about 1 mo of age. We examined the hypothesis that the marked dietary change that occurs at weaning might be important to this loss of O2 tolerance. We, therefore, prematurely weaned rat pups at 15-17 d of age, expecting to find an earlier loss of O2 tolerance. Surprisingly, the prematurely weaned rats showed consistently prolonged relative O2 tolerance compared with normally weaned rats at all ages tested from 35-85 d of life. For example, when challenged with greater than 95% O2 exposure for 7 d, the composite survival rate of the prematurely weaned rats (at 35-85 d of age) was nearly twice that of the normally weaned group (83 of 107 = 78% versus 44 of 107 = 41%, p less than 0.01). In the two experimental groups, nearly all comparative parameters examined were similar, including: 1) growth rate; 2) lung DNA, RNA, and protein; 3) lung antioxidant enzymes and enzyme responses to hyperoxia; 4) lung morphometry; and 5) lung elastin and collagen content. Only serum corticosterone and triiodothyronine levels differed considerably in the two groups. We conclude that premature weaning has a very marked and sustained positive effect on the relative retention of O2 tolerance in the growing rat.
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PMID:Premature weaning of rat pups results in prolongation of neonatal tolerance to hyperoxia. 185 32

Werner syndrome (WS) is a recessive genetic condition associated with markedly reduced replicative lifespans of cells in culture, high chromosomal instability in vivo and in vitro, and premature appearance of many characteristics of normal aging, including an increased incidence of cancer. We have monitored plasmid homologous recombination frequencies in diploid fibroblasts from 6 Werner or Werner-like syndrome patients, following transfection with a plasmid substrate containing 2 overlapping fragments of the TN5 Neor gene. Plasmid DNA recovered from these cells was then assayed for homologous recombination by (a) transformation of recA- bacteria to Ampr (indicating total viable plasmid) or Neor (indicating viable recombinant plasmid), and (b) by limited-cycle polymerase chain reaction (PCR) to co-amplify a recombinant fragment containing the overlap region, and a control region of the same plasmid, without bacterial transformation. Bacterial assay data indicated that recombination rates in 3 of the 6 WS strains were significantly elevated above normal controls; 4 of 6 appeared elevated by PCR assay. The highest-recombination WS strain showed evidence of reduced degradation of transfected plasmid DNA. For this small sample of WS strains, clinical severity of WS was not well correlated with recombination rate as determined by either assay (Pearson r = 0.78, not significant, for PCR assay); elevated recombination may, however, define a subset of WS at greatest risk for cancer and/or atherosclerosis. PCR assay of a hyperoxia-resistant HeLa cell line, displaying substantially increased chromosome breakage, indicated increased recombination between direct-repeat fragments. Nevertheless, elevated recombination in WS strains is unlikely to be secondary to impaired replicative capacity characteristic of WS cells, or to defective repair of chromosome damage which is increased in WS, since recombination in non-WS strains was unaffected by passage level or repeated UV irradiation.
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PMID:Homologous recombination is elevated in some Werner-like syndromes but not during normal in vitro or in vivo senescence of mammalian cells. 207 65

O2 toxicity of the central nervous system (CNS) may be a result of enhanced generation of reactive O2 species such as superoxide and H2O2 at high PO2. In this study, we measured H2O2 production in six regions of the rat brain before and after convulsions induced by hyperbaric hyperoxia (HBO). H2O2 concentration was determined ex vivo using a method based on the H2O2-dependent decline in catalase activity in the presence of the irreversible inhibitor of compound I, 3-amino-1,2,4-triazole. Regional catalase activity in the brain ranged from 0.029 +/- 0.004 to 0.055 +/- 0.004 mumol O2.min-1.micrograms DNA-1 in cerebellum and medulla-pons, respectively. In the presence of aminotriazole, catalase activity declined after HBO-induced convulsions to 26-45% of normoxic values. The rates of inactivation of catalase were used to predict average steady-state values for H2O2 concentration in different brain structures. Estimated H2O2 concentrations during HBO varied from 31 to 51 pM in cerebellum and posterior subcortex and represented increases of 2.2-7.3 times normoxic values. These findings suggest that H2O2 is an important mediator of selective neuronal vulnerability to CNS O2 toxicity.
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PMID:Regional H2O2 concentration in rat brain after hyperoxic convulsions. 227 69

Evidence suggests a positive correlation between metabolic rate (VO2), or ambient oxygen (O2) tension, and the rate of formation of free radicals from O2. We have previously demonstrated that the rates of growth, VO2, protein and DNA accumulation, and the activity of cytochrome oxidase (a key mitochondrial respiratory enzyme), are increased significantly by exposing the chick embryo to 72 h of hyperoxia (60% O2) late in incubation. To test the hypothesis that the chick embryo responds to a prenatal alteration in O2 availability in such a way as to protect its tissues from oxidative damage, we have used the thiobarbituric acid assay to estimate lipid peroxidation (a major form of free radical damage) in selected organs from chick embryos exposed to altered O2 availability. We found significantly higher concentrations of malondialdehyde (MDA, a secondary product of lipid peroxidation) in liver than in chorioallantoic membrane, brain, or heart. However, embryos exposed to brief (72 h) hypoxia (15% O2) or hyperoxia (60% O2) late in incubation, or 48 h of such exposure followed by 24 h of incubation in pure O2, exhibited no significant difference in MDA levels compared to normoxic (21% O2) controls in any of the tissues examined. We conclude that the increase in aerobic metabolism induced in the chick embryo by 3 days of hyperoxia is not accompanied by an increase in lipid peroxidation. We postulate that the chick embryo adapts to hyperoxia in such a way as to escape additional free radical damage, perhaps by increasing the capacity of its antioxidant defenses to compensate for a potential increase in the rate of free radical generation.
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PMID:Prenatal oxidative stress: I. Malondialdehyde in hypoxic and hyperoxic chick embryos. 237 60

The effects of oxidative stress on DNA damage and associated reactions, increased polyadenosine diphosphate-ribose polymerase (PARP) activity and decreased nicotinamide adenine dinucleotide (NAD) and adenosine triphosphate (ATP) contents, have been tested in primary cultures of porcine aortic endothelial cells. The cells were treated with 50-500 microM H2O2 for 20 min or 100 microM paraquat for 3 days or were exposed to 95% O2 for 2 and 5 days. The administration of 250-500 microM H2O2 resulted in a marked increase in PARP activity and a profound depletion of ATP and NAD. Although hyperoxia had no effect on PARP activity and reduced only slightly the ATP and NAD stores, it markedly reduced the ability of endothelial cells to increase PARP activity upon exposure to DNase. Paraquat had a similar effect. Human dermal fibroblasts were also exposed to 50-500 microM H2O2 for 20 min or 95% O2 for 5 days. Their response to H2O2 differed from that of endothelial cells by their ability to maintain the ATP content at a normal level. Fibroblasts were also insensitive to the effect of hyperoxia. These results suggest that the oxidant-related DNA damage is a function of the type of oxidative stress used and may be cell-specific.
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PMID:Differential effects of hyperoxia and hydrogen peroxide on DNA damage, polyadenosine diphosphate-ribose polymerase activity, and nicotinamide adenine dinucleotide and adenosine triphosphate contents in cultured endothelial cells and fibroblasts. 250 Apr 51

Cultured type II pneumocyte responses to in vitro normoxia (95% air:5% CO2) or hyperoxia (95% O2:5% CO2) were quantified. Normoxic culture (0 to 96 h) of rabbit type II cells resulted in enhanced cell-monolayer protein and DNA content. During this same time, cellular activities of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH Px) decreased. Compared to cultures maintained in normoxia, hyperoxic exposure of cultures resulted in decreased cell-associated protein and DNA content. Exposure to hyperoxia also resulted in cytotoxicity as demonstrated by elevated cellular release of DNA, lactate dehydrogenase (LDH), and preincorporated 8-[14 C]adenine. Cellular catalase and GSH Px activities in hyperoxic cells decreased similarly to normoxic controls. In contrast, cellular SOD activity in hyperoxic cells decreased less than in normoxic cultures. Cellular SOD activity in hyperoxic cultures, when normalized for cellular protein, but not DNA, was greater than normoxic values after 24 to 96 h of exposure. Unlike the decrease in cellular antioxidant enzymes during normoxic and hyperoxic culture, cellular LDH activity increased during both these exposures. Cellular LDH activity in 24 to 96 h hyperoxia-exposed cells increased to a lesser extent than normoxic controls. The extent of depression in LDH activity was dependent on whether the activity was normalized for cellular protein or DNA. Type II pneumocytes, which normally undergo hyperplasia and hypertrophy during hyperoxia in vivo, exhibited oxygen sensitivity in vitro. Exposure of type II cells to hyperoxia in vitro resulted in alterations in cellular SOD and LDH activities, but recognition of such changes were dependent on whether enzymatic activities were normalized for cellular DNA or protein.
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PMID:Responses of type II pneumocyte antioxidant enzymes to normoxic and hyperoxic culture. 250 12

Heart ventricles from chick embryos incubated in 60% O2 (hyperoxia) on the 16th through the 18th days of incubation were 21% heavier than those from control embryos maintained in 21% O2 (normoxia). Heart ventricles from embyros incubated in 15% O2 (hypoxia) were 8% lighter than controls. Changes in ventricular weight were accompanied by proportional changes in protein content (21% more in hyperoxic ventricles; 8% less in hypoxic ventricles). Ventricular tissue DNA content showed a significant increase in hyperoxia. Tissue protein/DNA ratios were significantly higher in hyperoxia and lower in hypoxia. These data suggest that increased O2 availability led to hypertrophy of chick embryo ventricular cells and an increase in the level of DNA synthesis. Cytochrome oxidase activity per mg DNA was 15-25% higher in hyperoxic ventricles than in hypoxic ventricles. This result is consistent with our previous findings that alterations in O2 availability affect the O2 consumption rate of the chick emryo in ovo, and it provides direct evidence that a phenomenon repeatedly observed in vitro is of importance in vivo. In contrast to the heart, O2 availability did not affect the wet weight, protein or DNA contents, or cytochrome oxidase activity of the chick embryo brain.
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PMID:O2 effect on composition of chick embryonic heart and brain. 255 50

Several aspects of tissue response to injury, including cell proliferation, cell migration, and deposition of extracellular matrix, have been attributed to platelet-derived growth factor (PDGF)-like cytokines. Because these responses play key roles in lung injury, PDGF-B (c-sis) gene expression was measured by Northern blot analysis of lung total RNA prepared after oxidant injury was induced by chronic exposure of rats to 85% oxygen for zero, 1, 3, and 7 days. Constitutive but low levels of PDGF-B mRNA (4.0 kb) were observed in the lungs of control animals exposed to 21% oxygen. Steady-state levels of PDGF-B mRNA in lung were elevated 2.5-fold by day 3 of hyperoxia and remained so up to at least day 7. The early increase in PDGF-B mRNA expression after 3 days of hyperoxic exposure preceded several other aspects of the reparative response. DNA synthesis measured by in vivo incorporation of [3H]thymidine into lung DNA was unchanged at day 3 but markedly elevated by day 7. A similar increase in extractable lung RNA implies a quantitative or qualitative change in extractable RNA at this later phase of tissue injury. Subtle changes in actin mRNA expression were also noted late in the course of lung injury. The content of cytoplasmic (beta,gamma) actin mRNA (2.1 kb) in lung was doubled after 7 days of hyperoxia (P less than 0.05). In addition, increased expression of an actin cDNA-hybridizing mRNA, which co-migrates with muscle-specific alpha-actin mRNA (1.7 kb), was detected on day 7, suggesting hyperplasia of smooth muscle and myofibroblasts. These data show that PDGF-B transcripts are constitutively expressed in rat lung tissue. The expression of PDGF-B mRNA increases early in the course of hyperoxic lung injury and precedes an increase in DNA synthesis and other responses that reflect tissue remodeling. These results suggest that the production of PDGF-like cytokines by cells within the lung itself initiates or modulates various aspects of lung injury and repair.
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PMID:Increased expression of PDGF-B (c-sis) mRNA in rat lung precedes DNA synthesis and tissue repair during chronic hyperoxia. 269 12

Newborn mammals in chronic hypoxia or hyperoxia experience, respectively, an increase or decrease in lung weight:body weight ratios, possibly because of the mechanical effect on the lung accompanying the ventilatory response. Because the avian lung does not expand or contract with the breathing cycle, we asked whether or not qualitatively similar changes could be observed in the lung of chick embryos incubated in hypoxic or hyperoxic conditions. Hypoxic embryos (10% O2, days 14-18) were smaller than controls incubated in normoxia, with higher hematocrit values and larger lung weight:body weight ratios (both wet and dry). Both the total pulmonary DNA (reflecting the cellular component) and the DNA concentration were decreased in hypoxia. Hyperoxic embryos (50% O2, days 7-18 or days 14-18) had lower hematocrit values and smaller dry lung weight:body weight ratios than controls, with similar DNA concentrations. In general, the differences from controls were more apparent in those embryos hyperoxic from day 14 to 18 of incubation than from day 7 to 18. We conclude that changes in lung weights qualitatively similar to those occurring in the chronically hypoxic or hyperoxic newborn mammal can also be observed in the hypoxic or hyperoxic chick embryo, suggesting that they are not necessarily caused by changes in mechanical stretch on the lung.
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PMID:Effects of hypoxia or hyperoxia on the lung of the chick embryo. 276 96

Cell death by oxidative stress has been proposed to be based on suicidal NAD depletion, typically followed by ATP depletion, caused by the NAD-consuming enzyme poly(ADP)ribose polymerase, which becomes activated by the presence of excessive DNA-strand breaks. In this study NAD+, NADH and ATP levels as well as DNA-strand breaks (assayed by alkaline elution) were determined in Chinese hamster ovary (CHO) cells treated with either H2O2 or hyperoxia to a level of more than 80% clonogenic cell killing. With H2O2 extensive DNA damage and NAD depletion were observed, while at a higher H2O2 dosage ATP also became depleted. In agreement with results of others, the poly(ADP)ribose polymerase inhibitor 3-aminobenzamide completely prevented NAD depletion. However, both H2O2-induced ATP depletion and cell killing were unaffected by the inhibitor, suggesting that ATP depletion may be a more critical factor than NAD depletion in H2O2-induced killing of CHO cells. With hyperoxia, only moderate DNA damage (2 X background) and no NAD depletion were observed, whereas ATP became largely (70%) depleted. We conclude that (1) there is no direct relation between ATP and NAD depletion in CHO cells subjected to toxic doses of H2O2 or hyperoxia; (2) H2O2-induced NAD depletion is not by itself sufficient to kill CHO cells; (3) killing of CHO cells by hyperoxia is not due to NAD depletion, but may be due to depletion of ATP.
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PMID:Effects of lethal exposure to hyperoxia and to hydrogen peroxide on NAD(H) and ATP pools in Chinese hamster ovary cells. 277 Jul 61


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