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

Superoxide dismutase is considered important in protection of aerobes against oxidant damage, and increased tolerance to oxidant stress is associated with induction of this enzyme. However, the importance of superoxide dismutase in this tolerance is not clear because conditions which promote the synthesis of superoxide dismutase likewise affect other antioxidant enzymes and substances. To clarify the role of superoxide dismutase per se in organismal defense against oxidant-generating drugs, we employed Escherichia coli transformed with multiple copies of the gene for bacterial iron superoxide dismutase. These bacteria have greater than ten times the superoxide dismutase activity of wild-type E. coli but, importantly, are normal in other oxidant defense parameters including catalase, peroxidases, glutathione, and glutathione reductase. High superoxide dismutase and control bacteria were exposed to the O2- -generating drug paraquat and to elevated pO2. We find; high superoxide dismutase E. coli are more readily killed by paraquat under aerobic, but not anaerobic, conditions. During exposure to paraquat, high superoxide dismutase E. coli accumulate more H2O2. Coincidentally, the reduced glutathione content of high superoxide dismutase E. coli declines more than in control E. coli. E. coli with high superoxide dismutase activity are also more readily killed by hyperoxia. Interestingly, the susceptibility of the parental and high superoxide dismutase E. coli to killing by exogenous H2O2 is not significantly different. Thus, under these experimental conditions, greatly enhanced superoxide dismutase activity accelerates H2O2 formation. The increased H2O2 probably accounts for the exaggerated sensitivity of high superoxide dismutase bacteria to oxidant-generating drugs. These results support the concept that the product of superoxide dismutase, H2O2, is at least as hazardous as the substrate, O2-. We conclude that effective organismal defense against reactive oxygen species may require balanced increments in antioxidant enzymes and cannot necessarily be improved by increases in the activity of single enzymes.
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PMID:Superoxide dismutase-rich bacteria. Paradoxical increase in oxidant toxicity. 354 14

Adult rats were exposed to room air, 50%, 65%, or 80% oxygen for 6 wk. Subsets were sacrificed periodically in order to establish alterations in growth parameters and lung antioxidant responses. Prolonged exposure to 50% or 65% oxygen did not result in weight loss or changes in lung-to-body weight ratios relative to control values. Treatment with 50% oxygen produced delayed increases in nonprotein sulfhydryl (NPSH) content and catalase (CAT) activity, while treatment with 65% oxygen produced delayed increases in NPSH, CAT, and glutathione peroxidase (GPx) content. Rats treated for 6 wk with either 50% or 65% oxygen died significantly earlier than room-air control animals when these groups were subsequently exposed to 100% oxygen. Rats exposed to 80% oxygen had significantly decreased body weight, increased lung-to-body weight ratios, and increased levels of NPSH, CAT, GPx, total superoxide dismutase, and glutathione reductase by 11 days of treatment. At 6 wk they had significantly altered growth parameters and increased GPx catalase, and NPSH levels. Their final antioxidant profile was not significantly different from 65% oxygen-exposed rats. However, these animals survived significantly longer than any group when exposed to 100% oxygen. In summary, lower concentrations of sublethal hyperoxia (less than or equal to 65%) were capable of eliciting significant antioxidant enzyme responses. Levels of antioxidant enzymes in the lungs of rats chronically exposed to sublethal hyperoxia did not appear to be solely responsible for enhanced survival in subsequent lethal hyperoxia.
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PMID:Adaptation to chronic hyperoxia. Biochemical effects and the response to subsequent lethal hyperoxia. 357

We compared the effects of 95% O2 (hyperoxia) alone, endotoxin (20 ng/ml) alone, and 95% O2 plus endotoxin on the release of lactate dehydrogenase (LDH), uptake of 5-hydroxytryptamine (5-HT), and antioxidant enzyme activities in porcine pulmonary arterial and aortic endothelial cells in monolayer culture. Hyperoxia increased LDH release and decreased 5-HT in both endothelial cell types. Hyperoxia also caused a decrease in catalase (CAT) activity and an increase in total superoxide dismutase (SOD) and glutathione reductase (GSH-Red) activities in both cell types. Endotoxin alone had no effect on LDH release, 5-HT uptake, or antioxidant enzyme activities. However, endotoxin prevented the hyperoxic increase in LDH release and the hyperoxic decrease in 5-HT uptake. Endotoxin plus 95% O2 had no consistent effect on the antioxidant enzyme profile in pulmonary artery or aortic endothelial cells. These results indicate that (1) hyperoxia injures both pulmonary artery and aortic endothelial cells in culture and causes changes in the antioxidant enzyme profile that are similar in the two cell types; (2) hyperoxia-induced decreases in CAT activity and increases in SOD activity may be responsible for increased sensitivity of endothelial cells to O2 toxicity; and (3) endotoxin protects against hyperoxic injury to endothelial cells in vitro, but increases in antioxidant enzyme activities are not the mechanism for this protection.
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PMID:Effect of oxygen and endotoxin on lactate dehydrogenase release, 5-hydroxytryptamine uptake, and antioxidant enzyme activities in endothelial cells. 388 60

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

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

The anticancer drug 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) inhibits glutathione reductase, an enzyme involved in oxidant defense systems. The 30-day LD50 for BCNU in male and female BALB/c mice was 52 and 46 mg/kg, respectively. A 35-mg/kg BCNU dose was not lethal to any animal. Glutathione reductase was inhibited in lung tissue by about 50% for 4 days following a single 35 mg/kg dose of BCNU. The prolonged inhibition of glutathione reductase by BCNU suggested this drug might enhance pulmonary oxygen toxicity by diminishing the lung's antioxidant capacity. Exposing mice treated with 35 or 50 mg/kg BCNU to continuous 85% oxygen decreased the LT50 from 13.1 to 6.3 and 5.3 days, respectively, compared to vehicle-treated controls. All mice treated with 35 mg/kg BCNU or vehicle and exposed to 85% oxygen only on Days 0-4 survived to Day 30. Extending the hyperoxic exposure 1 additional day resulted in the death of all BCNU-treated mice, while 70% of the vehicle-treated mice survived to Day 30. Pulmonary glutathione peroxidase, catalase, and superoxide dismutase activities were unaffected up to 6 days following 35 mg/kg BCNU, 85% oxygen, or both. Pulmonary glutathione reductase activity was unaffected by 85% oxygen alone, although hyperoxia extended the BCNU-induced inhibition of this enzyme to Day 6. BCNU, 35 mg/kg, had little effect on lung reduced glutathione (GSH) levels. A significant decrease was only measured on Day 4. Hyperoxia, either alone or with BCNU, had no effect on lung GSH content.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enhanced oxygen toxicity following treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea. 651 Jun 7

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

The effects of parenteral vitamin E treatment on aspects of the pulmonary biochemical and morphologic response to 100% oxygen were studied in newborn rabbits manifesting chemical evidence of vitamin E deficiency. Pups treated with 2 mg/100 g body weight increased serum vitamin E levels from 0.39 to 2.17 mg/dl by 72 hr and lung tissue vitamin E content from 3.52 to 17 mg/mg wet weight of lung. In vitro lipid peroxidation in lung homoginates of animals in 100% oxygen for 72 hr was inhibited by approximately 80% in animals receiving 100% oxygen plus vitamin E. Hyperoxia-induced increases in the pulmonary antioxidant enzymes, superoxide dismutase, glutathione peroxidase, and glutathione reductase were diminished by vitamin E administration. Lungs from vitamin E-treated animals did not show the early lung epithelial injury seen in animals exposed to 100% oxygen but not treated with vitamin E. Mophometric analysis of lungs of animals in room air for 72 hr showed 81.6% of lung to be normal as compared with 43.3% normal lung in the group maintained in 100% oxygen for 72 hr. In the group treated with oxygen plus vitamin E, the lungs were similar to room air controls (82.6% normal). This study thus provides further evidence for a direct antioxident affect of vitamin E in lung.
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PMID:Vitamin E affects lung biochemical and morphologic response to hyperoxia in the newborn rabbit. 722 Jan 49

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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