UMLS:C0242706 - FACTA Search

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

The time course and nature of the pulmonary inflammatory and antioxidant responses, both during and after hyperoxic-induced acute lung injury were studied in the preterm guinea pig. Three-day preterm (65 days gestation) guinea pigs were randomly exposed to either 21% O2 (control) or 95% O2 (hyperoxia) for 72 hours. All pups were then maintained in ambient conditions for up to a further 11 days, during which time lung damage was monitored. In animals exposed to hyperoxia, evidence of acute lung injury and inflammation was characterized by a marked increase in microvascular permeability and elevated numbers of neutrophils in bronchoalveolar lavage fluid. Protein concentration, elastase-like activity and elastase-inhibitory capacity in lavage fluid were at a maximum at the end of the 72 hours hyperoxic exposure. Four days later, all values had returned to control levels. In contrast, increased numbers of neutrophils, macrophages and lymphocytes were recovered in the lavage fluid during this early recovery period. Coinciding with the influx of inflammatory cells, there was a significant increase in glutathione peroxidase, manganese superoxide dismutase and catalase activities in immature lung. Lung copper/zinc superoxide dismutase activity remained unchanged during both experimental periods. The strong temporal relationship between the influx of inflammatory cells to the lung and the induction of pulmonary antioxidant enzyme defences suggests that a common mechanism underlies both responses. These findings have led us to regard inflammation in the hyperoxic-injured immature lung as a beneficial event and not, as previously suggested, as part of the injurious process.
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PMID:Temporal association between pulmonary inflammation and antioxidant induction following hyperoxic exposure of the preterm guinea pig. 837 May 48

Tolerance to hyperoxia usually requires an increase of lung antioxidant enzyme (AOE) activity. We used rats with different degrees of tolerance to > 95% O2 to evaluate the importance of individual AOEs for tolerance; we also explored the regulation of AOE gene expression. During exposure of adult rats to > 95% O2, lung manganese superoxide dismutase (MnSOD) activity fell approximately 50% despite a threefold increase of MnSOD mRNA concentration; addition of a reducing agent to lung extracts from O2-exposed rats partially restored MnSOD activity. Endotoxin induced tolerance to O2 (a) without elevating Cu,Zn superoxide dismutase activity, (b) with increases of catalase and glutathione peroxidase (GP) activity of the same magnitude as occurred in O2-saline rats, but (c) with MnSOD activity 1.5-1.9-fold higher than in air-saline rats and 1.4-3.6-fold higher than in O2-saline rats. Endotoxin elevated the concentration of MnSOD and GP mRNAs without increasing their stability. O2 elevated MnSOD mRNA concentration, and increased its stability. O2 plus endotoxin increased the concentration and stability of MnSOD, catalase, and GP mRNAs. These data suggest that in adult rats tolerance to hyperoxia requires increased MnSOD activity; the data show gene expression and regulation vary among the AOEs, and that increased stability of the AOEs' mRNAs plays an important role in AOE gene expression and in tolerance to hyperoxia.
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PMID:Tolerance of rats to hyperoxia. Lung antioxidant enzyme gene expression. 843 58

Although prenatal steroid therapy is known to enhance in utero maturation of the surfactant and antioxidant enzyme systems, little is known about the effects of steroids on the antioxidant system after birth. We measured activities of the antioxidant enzymes, catalase, superoxide dismutase, and glutathione peroxidase, in lung homogenates from both preterm and term rat pups after prenatal dexamethasone treatment. Enzyme activities were measured at birth and after exposure to > 98% oxygen. Dexamethasone treatment resulted in significantly higher survival of the preterm pups at 24 h (91.3% for dexamethasone versus 57% for saline). In preterm pups, the activities of catalase and superoxide dismutase at birth were higher after dexamethasone treatment (p < 0.05). However, after 24 h of hyperoxic exposure, there were no differences in activities of any of the antioxidant enzymes between the dexamethasone and control groups of prematurely born pups. In term pups, antioxidant enzyme activities did not differ significantly at birth; nor did they differ after 24 to 72 h of hyperoxic exposure in the dexamethasone and control treatment groups. Our results indicate that although prenatal dexamethasone treatment augments survival and catalase and superoxide dismutase activities at birth in preterm rat pups, dexamethasone does not result in altered early postnatal antioxidant enzyme activities after exposure to hyperoxia.
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PMID:Antioxidant enzyme responses to hyperoxia in preterm and term rats after prenatal dexamethasone administration. 843 92

NAD(P)H:quinone reductase, or DT-diaphorase, has been studied primarily in the liver where it appears to function as an antioxidant-like enzyme in the 2-electron reduction of some quinones to less toxic hydroquinones. This property together with new molecular biology evidence that oxidants such as H2O2 can induce gene transcription of DT-diaphorase provide especially intriguing reasons to examine the possibility that lung DT-diaphorase could have an important antioxidant enzyme role versus pulmonary O2 toxicity during exposure to hyperoxia. We found that similar to the 'classical' lung antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) DT-diaphorase activity increased significantly in the late gestational fetal lung; also its activity was altered in the same way as the antioxidant enzymes by prenatal hormonal treatment. Another similarity is that DT-diaphorase activity was induced in the neonatal animal lung during hyperoxia, but not in the adult animal lung. However, using various drug treatments which markedly increased lung DT-diaphorase activity (e.g., 3-methylcholanthrene, butylated hydroxyanisole, methimazole) we found no improved hyperoxic survival in the treated adult rats. Also, dicumarol treatment, which markedly depressed DT-diaphorase activity, did not diminish the hyperoxic survival rate in an O2-tolerant adult rat model. Thus, we conclude that unlike the classical antioxidant enzymes, increased pulmonary DT-diaphorase activity is probably neither necessary nor sufficient to protect against pulmonary O2 toxicity during hyperoxia.
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PMID:Does lung NAD(P)H:quinone reductase (DT-diaphorase) play an antioxidant enzyme role in protection from hyperoxia? 846 17

The 27-day-old rat exposed to 100% oxygen (O2) for 8 days will have predictable lung vascular and parenchymal changes at 60 days of age. Using this model, the goals of this study are (1) to measure the lung antioxidant enzyme activities serially following intratracheal PEG antioxidant therapy during the 8-day O2 exposure; and (2) to assess chronic cardiopulmonary changes in the O2-exposed rats treated with PEG-CAT and/or PEG-CuZn SOD given intraperitoneally (IP) and/or intratracheally (IT). The study encompassed 202 male rats exposed to room air or oxygen. CuZn SOD doses were 300 U IT and 2000 U IP. The CAT dose was 500 or 4000 U IT and 10,000 U IP. At 60 days of age, the right ventricular systolic pressure (RVP), RV weight, % acinar wall arterial thickness, and parenchymal air space were significantly increased in O2-exposed rats compared to RA rats. The RVP, RV weight, and parenchymal changes were prevented by daily IT PEG-CAT 4000 U + CuZn SOD 300 U but the increased small artery muscularization was not. Three hours after the initial dose of IT PEG-CAT 4000 U, lung CAT activity was more than doubled and remained constant throughout the 8-day daily treatment course. This dose of CAT depressed the induction response to O2 of CuZn and MnSOD. It is concluded that daily intratracheal administration of PEG-CAT 4000 U + CuZn SOD 300 U can significantly ameliorate some of the chronic parenchymal and vascular lung O2 toxic changes. However, it appears that high-dose exogenous PEG-CAT suppresses the endogenous enzyme induction to hyperoxia of both CuZn and Mn-SOD.
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PMID:Lung antioxidant enzymes and cardiopulmonary responses in young rats exposed to hyperoxia and treated intratracheally with PEG catalase and superoxide dismutase. 846 59

Antenatal cocaine administration is associated with increases in catecholamines and glucocorticoids and results in fetal hypoxemia, with the speculated potential for increased free radical formation in the fetus. Because of this, we hypothesized that antenatal cocaine exposure would produce not only accelerated pulmonary surfactant maturation, but also stimulation of antioxidant enzyme (AOE) system maturation and the ability to mount a protective AOE response to hyperoxia as well. Seventy-two, 48, and 24 h before delivery at either 20, 21, or 22 d of gestation, pregnant rats received twice daily s.c. injections of cocaine hydrochloride (40 mg/kg) or saline. Off-spring demonstrated growth retardation with significant reduction in body weight at all 3 gestational d studied that persisted to the 5th postnatal d. Serum corticosterone and total catecholamines were elevated from 50 to 200% in cocaine-exposed adult rats and pups. Advanced surfactant development in cocaine-exposed fetal offspring was apparent at d 21 of gestation, with significant increases in lung disaturated phosphatidylcholine content in cocaine (3.94 +/- 0.67 mg/g lung) versus control (3.25 +/- 0.64) offspring (p < 0.01). No increases in AOE maturation were found in cocaine-exposed fetuses at all 3 gestational d studied, whereas a significant decrease was demonstrated in glutathione peroxidase activity at d 20 and 22 of gestation in cocaine-exposed fetuses. In addition, cocaine newborns manifested a protective AOE response to hyperoxia of a magnitude similar to that of control newborns.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antenatal cocaine exposure produces accelerated surfactant maturation without stimulation of antioxidant enzyme development in the late gestation rat. 847 10

It has been previously shown that prophylactic, intravenous dexamethasone (DEX) and intratracheal recombinant human Cu/Zn superoxide dismutase (SOD) ameliorate lung injury in newborn piglets treated with 48 hr of hyperoxia and mechanical ventilation. DEX has many pharmacologic effects, including the possible induction of antioxidant enzyme systems. To investigate whether the effects of DEX are mediated by an increase in endogenous antioxidant enzyme activity, 5 groups of term newborn piglets were studied: Group 1 piglets were ventilated with room air for 48 hr; Group 2 animals were ventilated with 100% O2 for 48 hr; Group 3 animals were ventilated with room air for 48 hr and received DEX (0.7 mg/kg) every 12 h; Group 4 were ventilated with 100% O2 for 48 hr and also received DEX; Group 5 animals were no ventilated and were sacrificed at time 0. At the conclusion of the studies, bronchoalveolar lavage (BAL) was performed and the lungs were removed and homogenized. Lung tissue and BAL were analyzed for SOD, catalase, GPX activities, and total protein concentration. No significant differences in any of these assays were seen in either lung tissue or BAL in the 5 groups. These observations indicate that 48 hr of hyperoxia, mechanical ventilation, or dexamethasone treatment does not induce activity of SOD, catalase, or glutathione peroxidase (GPX) in the lungs of newborn piglets. Thus postnatal DEX appears to minimize neonatal lung injury by mechanisms that are independent of these enzymes.
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PMID:The effects of hyperoxia, mechanical ventilation, and dexamethasone on pulmonary antioxidant enzyme activity in the newborn piglet. 857 Mar

Tolerance to hyperoxia usually depends on an increase in lung antioxidant enzyme activity. Antioxidant-surfactant liposomes, encapsulating the antioxidant enzymes CuZn-superoxide dismutase (CuZnSOD) and catalase in synthetic surfactant lipids, increase lung antioxidant activity following intratracheal instillation in premature and term rabbits. We investigated whether the exogenous antioxidant enzymes encapsulated in these liposomes inhibit the endogenous antioxidant enzyme synthesis in the premature rabbit lung. Premature rabbits, delivered at 28 days of gestation, were treated intratracheally with antioxidant-surfactant liposomes, surfactant liposomes without antioxidant enzymes, or air placebo at birth and exposed to hyperoxia for 24 h. A comparison group was killed after breathing room air at birth. The right lungs of the pups were assayed for CuZnSOD and catalase activities and DNA content, the left lungs of the same pups were used to quantitate the concentrations of CuZnSOD and catalase mRNA using cRNA probes. Lung CuZnSOD and catalase mRNA quantities increased during exposure to hyperoxia, but were not affected by exogenous antioxidant enzymes. These data suggest that intratracheal instillation of CuZnSOD and catalase does not down-regulate mRNA transcription of these antioxidant enzymes in the premature rabbit lung.
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PMID:Lung CuZn-superoxide dismutase and catalase gene expression in premature rabbits treated intratracheally with antioxidant-surfactant liposomes. 898 40

Although the effect of hyperoxia on antioxidant enzymes is well known, the effect of subtoxic levels of hyperoxia on gamma-glutamyltransferase (gamma-GT), involved in the degradation and uptake of extracellular GSH for intracellular GSH synthesis, is unknown. The aim of the study was to investigate (1) the effects of in vitro hyperoxia on gamma-GT activity of type II cells and (2) the effects of the lazaroid U-74389G and N-acetylcysteine (NAC) on the hyperoxia-induced changes in gamma-GT and antioxidant enzyme activities. At 48 h after isolation, rat type II cells were exposed for 2 days to air, 60% O2 or 85% O2 with or without 30 microM U-74389G or 100 microM NAC. After the exposure, the cells were harvested and assayed for superoxide dismutase (SOD), glutathione peroxidase (GPx), gamma-GT activity, and GSH levels. In another series of experiments 85% O2-exposed cells, with or without U-74389G, were used for Northern blotting of gamma-GT mRNA. Exposure to 60% O2 decreased gamma-GT and GSH by -47 and -34%, respectively, while SOD and GPx activities remained unchanged. After 85% O2-exposure gamma-GT decreased by -55%, SOD and GPx increased by +55 and +87%, respectively, while GSH decreased by -35%. NAC treatment decreased gamma-GT activity by -42% in the air-exposed cells. After 60% O2, U-74389G led to significantly higher gamma-GT (+117%) and GSH (+26%) while NAC only led to higher GSH (+28%) compared to the oxygen-exposed cells not treated with NAC or U-74389G. After 85% O2 U-74389G increased gamma-GT, SOD, and GSH by +72, +58, and +68%, respectively, while NAC only increased SOD (+49%) and GSH (+26%) compared to the oxygen-exposed cells not treated with NAC or U-74389G. The 85% O2 exposure, with or without U-74389G, had no effect on gamma-GT mRNA levels. The results show that hyperoxia decreases rat type II cell gamma-GT activity in vitro. This effect was not related to an altered regulation at mRNA level and it was not associated with the hyperoxia-induced decrease in intracellular GSH, since restoration of the GSH levels by NAC did not restore gamma-GT activity. The lazaroid U-74389G with vitamin E-like properties effectively prevented the decrease in gamma-GT and GSH, so that direct inactivation of the membrane-bound gamma-GT by hyperoxia is the most likely mechanism.
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PMID:Decrease in gamma-glutamyltransferase activity in rat type II cells exposed in vitro to hyperoxia: effects of the 21-aminosteroid U-74389G. 920 59

Dystrophin-deficiency results in degeneration of most, but not all, skeletal muscles. The mechanisms responsible for degeneration of limb muscle and sparing of extraocular muscle are not known. To address the notion that muscle pathology may be free radical-mediated, we evaluated antioxidant enzyme activities and lipid peroxidation products (TBARS) content in mdx and control mice. TBARS content and the activities of total superoxide dismutase, selenium dependent glutathione peroxidase, glucose-6-phosphate dehydrogenase and catalase were consistently higher in both affected and spared muscles of mdx mice. These data suggest that oxidative stress may be constitutively present in mdx muscle, but may not be the principal pathogenic mechanism. To further test the hypothesis of oxidative stress involvement in dystrophinopathies, control strain and mdx mice were subjected to chronic hyperoxia. The pattern of antioxidant enzyme activities and TBARS content from hyperoxic control strain mice was similar to that of normoxic mdx mice, suggesting that a similar level of oxidative stress was induced. In conclusion, this study has provided indirect evidence for oxidative stress in dystrophin-deficient muscle.
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PMID:Oxidative stress as a potential pathogenic mechanism in an animal model of Duchenne muscular dystrophy. 932 2

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