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

Diethylmaleate (DEM) decreases glutathione (GSH) levels in various organs by enzymatic conjugation with reduced GSH catalyzed by GSH transferase. We have examined levels of GSH, glutathione reductase (GR), and glucose-6-phosphate dehydrogenase (G6PD) in lungs of 200-250-g rats after intraperitoneal injection of 0.5 or 1 g DEM/kg body wt. The GSH levels are severely depressed at 2 and 4 h but have essentially recovered by 12 and 24 h after either dose of DEM. The GR and G6PD activities in the 1 g/kg group are depressed at 4 h to a lesser extent than the GSH levels and also return to normal by 12 and 24 h. These enzymes are not affected in the 0.5 g/kg group. To determine whether these transient decreases in GSH and related enzymes affected O2 tolerance, we exposed rats injected with DEM to greater than 98% O2 and found that halftime (t1/2) for survival was decreased in rats receiving both 0.5 and 1 g DEM/kg body wt when compared with untreated or saline-injected controls (t1/2 control, 74 h; 0.5 g DEM, 59 h; 1 g DEM, 53 h). No deaths occurred in air controls at 1 mg/kg DEM for up to 5 days. DEM, in itself, caused no morphological alteration of the lung. Thus a decrease in lung GSH and related enzymes, occurring by 4 h and reversed by 12 h, has a significant effect on the subsequent progression of lung pathology and indicates that early biochemical events occurring in lungs exposed to hyperoxia may be very important in determining the degree of longer-term damage to rat lungs.
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PMID:Transient depletion of lung glutathione by diethylmaleate enhances oxygen toxicity. 398 Mar 59

We used a nutritional deprivation model to produce intrauterine growth-retarded (IGR) rat pups (birth weight = approximately 75% of normal). The IGR newborns evidenced a marked reduction in tolerance to greater than 95% O2 exposure: 10-day survival = 10/47 (21%) versus 18/36 (50%) for control pups, and LT50 = 7.2 days versus 10 days for controls (p less than 0.01). Various lung parameters at birth and during O2 exposure were examined to try to define why prenatal undernutrition should compromise the survival of IGR rats in hyperoxia. We found decreased lung glutathione peroxidase and glucose-6-phosphate dehydrogenase activity (with normal superoxide dismutase and catalase levels) in the IGRs at birth; decreased lung disaturated phosphatidylcholine content (even more markedly decreased in 1-day premature pups); and decreased lung surface area/body weight. These factors and other features of newborn IGRs reported in the literature may help to explain how prenatal undernutrition compromises postnatal tolerance to prolonged high-O2 exposure.
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PMID:Intrauterine growth-retarded rat pups show increased susceptibility to pulmonary O2 toxicity. 398 89

Total glutathione levels and the activity of enzymes associated with antioxidant protection in neonatal lung are increased in response to hyperoxia. Glutathione levels in developing rat lung decreased from 24 nmol/mg protein on day 19 of gestation to approximately 12 nmol/mg protein at birth. The initial decrease in glutathione may be due to emergence of other antioxidant systems. Newborn rats placed in 100% oxygen showed a rapid and sustained increase in total glutathione levels which was primarily due to an increase in reduced glutathione. Explants obtained from 16-wk gestation human fetal lung or from 17- to 18-day fetal rat lung also showed increased total and reduced glutathione when cultured in 95% oxygen, 5% CO2 as compared with explants cultured in room air. Type II cells isolated from neonatal rats maintained in oxygen for 6 days also showed glutathione levels twice those found in cells isolated from animals in room air. The activity of antioxidant enzymes (glucose-6-phosphate dehydrogenase, glutathione peroxidase, glutathione reductase) was increased in lungs of newborn rats exposed to 100% oxygen either at birth or 2 days of age. Antioxidant enzyme activity of lung explants cultured in 95% oxygen, 5% CO2 was also higher than in explants maintained in room air. These results suggest that the increases in glutathione and of antioxidant enzymes in vivo and in vitro are a direct effect of oxygen exposure in lung and that the increase of both glutathione and antioxidant enzyme activity is intrinsic to the lung cell itself. It is likely that increases in glutathione in lung represent an important protective mechanism against oxidant injury.
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PMID:The responses of glutathione and antioxidant enzymes to hyperoxia in developing lung. 403 84

Preexposure of adult rats to ozone (0.8 +/- 0.1 ppm for 7 days) has been found to produce a marked degree of tolerance to hyperoxia (greater than 95% O2). The survival of O3-preexposed rats in hyperoxia for 168 h was 28 of 32 (88%) compared with a rate of 2 of 18 (11%) for nonpreexposed rats. Total lung superoxide dismutase (SOD), glutathione peroxidase (GP), glucose 6-phosphate dehydrogenase (G6-PD), and catalase (CAT) activities were all significantly increased after O3 preexposure and after the subsequent hyperoxic challenge. Probable mechanisms accounting for the markedly improved survival in hyperoxia after O3 preexposure include both increased lung antioxidant enzyme and repair of structural damage by proliferation of alveolar lining cells. The demonstration of cross-tolerance between the atmospheric oxidants O3 and O2 suggests that there are similarities in the lung's adaptation to both oxidants.
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PMID:Ozone-induced tolerance to hyperoxia in rats. 670

Rats exposed to 10 to 11 per cent oxygen for 7 days develop tolerance to hyperoxia and can survive for prolonged periods in 100 per cent oxygen. This preexposure to hypoxia is associated with a 180 per cent increase in the activity of the mangani superoxide dismutase but no increase in activity of copper-zinc superoxide dismutase, glucose-6-phosphate dehydrogenase, or the mitochondrial enzymes, cytochrome oxidase and succinate cytochrome c reductase. Cyanide-insensitive oxygen uptake is also increased after this exposure to hypoxia suggesting that an enhanced rate of production of partially reduced species of oxygen may occur. Morphometric and morphologic studies of lung structure demonstrate that no substantial change in cell population characteristics occur in the lungs of animals exposed to hypoxia, but there are ultrastructure changes in the cytoplasm of pulmonary capillary endothelial cells consistent with focal hypertrophy and enhanced metabolic activity of these cells.
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PMID:Structural and biochemical adaptive changes in rat lungs after exposure to hypoxia. 682 93

Rats fed 3% casein diets for 6 days showed an increased susceptibility to greater than 98% oxygen [mean survival time 46.9 +/- 4.1 (SD) h] compared with animals fed 25% casein diets (mean survival time 60 +/- 5 h). The 3% casein diet did not reduce the responses to hyperoxia of lung glucose-6-phosphate dehydrogenase, glutathione peroxidase, and glutathione reductase (NAD(P)H), which maintain tissue levels of reduced glutathione or lung superoxide dismutase levels. While supplementation of the 3% casein diet with the sulfur-containing amino acids (cysteine, cystine, or methionine) prevented the increased oxygen toxicity, supplementation with leucine, a nonsulfur-containing amino acid, had no effect on potentiation of toxicity. Animals fed the unsupplemented 3% casein diet failed to show an elevation of lung glutathione in response to hyperoxia. When the 3% casein diet was supplemented with cysteine, total lung glutathione levels increased normally during oxygen exposure. Supplementation of the 25% protein diet with cysteine did not further protect these animals. We conclude that potentiation of oxygen toxicity by dietary protein deficiency in the rat is due to the low sulfur-containing amino acid content of the diet; the mechanism of increased toxicity by hyperoxia is probably related to an inability to increase glutathione levels due to a shortage of the cysteine component of the glutathione tripeptide.
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PMID:Potentiation of oxygen toxicity in rats by dietary protein or amino acid deficiency. 682 98

Adult rats preexposed to 10% O2 for 3 days had marked tolerance to hyperoxia-induced lung damage and lethality. The survival of preexposed vs. nonpreexposed rats at 72 h of hyperoxic exposure was 62/62 vs. 7/47 (15%), P less than 0.0001; and after 7 days in 96-98% O2, the comparative survival was 31/33 (94%) vs. 1/20 (5%), P less than 0.0005. Hypoxic exposure produced significant elevations in rat lung superoxide dismutase, catalase, glutathione peroxidase, and glucose-6-phosphate dehydrogenase activities. In contrast, in adult mice and hamsters, no increased lung antioxidant enzyme levels were produced by preexposure to hypoxia and no significant tolerance to high O2 was realized. (Lethal time50 values for hypoxia-preexposed and nonpreexposed mice, 5.2 and 4.4 days, respectively; and for hamsters, 6.4 and 6.1 days, respectively.) Thus the protective effect of hypoxic preexposure is correlated with adaptive changes in lung antioxidant enzyme activity. Evidence in the literature suggests that superoxide anion (O-2) and H2O2 production may increase under hypoxic conditions. Increased cellular concentrations of their normal substrates could stimulate antioxidant enzyme rises during the preexposure period in hypoxia.
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PMID:Protection from O2 toxicity by preexposure to hypoxia: lung antioxidant enzyme role. 711 67

Bacterial endotoxin has a marked protective effect against pulmonary O2 toxicity in rats placed directly in atmospheres of greater than 95% O2. To determine whether endotoxin treatment during exposure to relatively low levels of hyperoxia would protect rats from the accelerated O2 toxicity that normally occurs when these rats are transferred to greater than 95% O2, we gave endotoxin or saline 1) during exposure to 40% O2 (5 days), or 2) during exposure to 40%-60%-85% O2 (2 days at each level). Saline-treated rats showed significantly decreased tolerance on transfer to greater than 95% O2 [LT50 = 47.5 h (exposure 1) and 48.5 h (exposure 2)] compared with normal nonpreexposed rats (LT50 = 66 h). In contrast, endotoxin-treated rats showed a marked tolerance on transfer to greater than 95% O2 [% of rats surviving 72 h = 14/16 (88%) endotoxin-treated vs. 2/16 (13%) saline-treated]. The endotoxin-treated rats, unlike the saline-treated rats, showed significant elevations in lung superoxide dismutase, catalase, glutathione peroxidase, and glucose-6-phosphate dehydrogenase levels after the O2 preexposure periods; this may account for their significantly improved tolerance when challenged with greater than 95% O2 exposure.
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PMID:Endotoxin reverses the decreased tolerance of rats to greater than 95% O2 after preexposure to lower O2. 732 58

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

The brain has been suggested to be especially sensitive to damage by reactive oxygen species. In this study, we examined the effects of hyperoxic conditions on the activities and mRNA levels of antioxidant enzymes in reaggregation cultures of rat forebrain cells. Cultures were exposed to 80% oxygen for 12-60 h starting on Days 17 and 33 in culture. Superoxide dismutase activities and mRNA levels were not affected by hyperoxia, whereas catalase activity was slightly decreased after 24 h in 80% oxygen at Day 17. Glutathione peroxidase activity was markedly decreased already after 12 h of hyperoxia, and decreased activities of glutathione reductase and glucose-6-phosphate dehydrogenase were also noted. The glutathione peroxidase mRNA levels were increased in hyperoxic cultures at Day 17 but not at Day 33. These results suggest that the enzymatic defense mechanisms against reactive oxygen species in the brain are rather weak and deteriorate during oxidative stress but that a potential for compensatory upregulation exists at least during the first postnatal weeks.
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PMID:Oxidative stress decreases antioxidant enzyme activities in reaggregation cultures of rat brain cells. 786 67


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