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

Newborn children can be exposed to high oxygen levels (hyperoxia) for hours to days during their medical and/or surgical management, and they also can have poor myocardial function and hemodynamics. Whether hyperoxia alone can compromise myocardial function and hemodynamics in the newborn and whether this is associated with oxygen free radical release that overwhelms naturally occurring antioxidant enzymes leading to myocardial membrane injury was the focus of this study. Yorkshire piglets were anesthetized with pentobarbital sodium (65 mg/kg), intubated, and ventilated to normoxia. Once normal blood gases were confirmed, animals were randomly allocated to either 5 h of normoxia [arterial Po(2) (Pa(O(2))) = 83 +/- 5 mmHg, n = 4] or hyperoxia (Pa(O(2)) = 422 +/- 33 mmHg, n = 6), and myocardial functional and hemodynamic assessments were made hourly. Left ventricular (LV) biopsies were taken for measurements of antioxidant enzyme activities [superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT)] and malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) as an indicator of oxygen free radical-mediated membrane injury. Hyperoxic piglets suffered significant reductions in contractility (P < 0.05), systolic blood pressure (P < 0.03), and mean arterial blood pressure (P < 0.05). Significant increases were seen in heart rate (P < 0.05), whereas a significant 11% (P < 0.05) and 61% (P < 0.001) reduction was seen in LV SOD and GPx activities, respectively, after 5 h of hyperoxia. Finally, MDA and 4-HNE levels were significantly elevated by 45% and 38% (P < 0.001 and P = 0.02), respectively, in piglets exposed to hyperoxia. Thus, in the newborn, hyperoxia triggers oxygen free radical-mediated membrane injury together with an inability of the newborn heart to upregulate its antioxidant enzyme defenses while impairing myocardial function and hemodynamics.
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PMID:Hyperoxia causes oxygen free radical-mediated membrane injury and alters myocardial function and hemodynamics in the newborn. 1527 98

Experimental hyperoxia represents a suitable in vitro model to study some pathogenic mechanisms related to oxidative stress. Moreover, it allows the investigation of the molecular pathophysiology underlying oxygen therapy and toxicity. In this study, a modified experimental set up was adopted to accomplish a model of moderate hyperoxia (50% O(2), 96 h culture) to induce oxidative stress in the human leukemia cell line, U-937. Spectrophotometric measurements of mitochondrial respiratory enzyme activities, NMR spectroscopy of culture media, determination of antioxidant enzyme activities, and cell proliferation and differentiation assays were performed. The data showed that moderate hyperoxia in this myeloid cell line causes: i) intriguing alterations in the mitochondrial activities at the levels of succinate dehydrogenase and succinate-cytochrome c reductase; ii) induction of metabolic compensatory adaptations, with significant shift to glycolysis; iii) induction of different antioxidant enzyme activities; iv) significant cell growth inhibition and v) no significant apoptosis. This work will permit better characterization the mitochondrial damage induced by hyperoxia. In particular, the data showed a large increase in the succinate cytochrome c reductase activity, which could be a fundamental pathogenic mechanism at the basis of oxygen toxicity.
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PMID:Mitochondrial damage and metabolic compensatory mechanisms induced by hyperoxia in the U-937 cell line. 1546 33

Overexpression of peroxiredoxin 6 (Prdx6) has been shown to protect lungs of mice against hyperoxia-mediated injury. In this study, we evaluated whether genetic inactivation of Prdx6 in mice increases sensitivity to oxygen toxicity. We evaluated mouse survival, lung histopathology, total protein and nucleated cells in bronchoalveolar lavage fluid (BALF), and oxidation of lung protein and lipids by measurement of protein carbonyls and thiobarbituric reactive substances (TBARS), respectively. The duration of survival for Prdx6 -/- mice was significantly shorter than that observed in wild-type mice on exposure to 85 or 100% O(2); survival of Prdx6 +/- mice was intermediate. After 72-h exposure to 100% O(2), lungs of Prdx6-/- mice showed more severe injury than wild-type with increased wet/dry weight, epithelial cell necrosis and alveolar edema on microscopic examination, increased protein and nucleated cells in BALF, and higher content of TBARS and protein carbonyls in lung homogenate. These findings show that Prdx6 -/- mice have increased sensitivity to hyperoxia and provide in vivo evidence that Prdx6 is an important lung antioxidant enzyme.
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PMID:Lung injury and mortality with hyperoxia are increased in peroxiredoxin 6 gene-targeted mice. 1552 33

Peroxiredoxin 6 (Prdx6), a bifunctional 25-kDa protein with both GSH peroxidase and phospholipase A2 activities, is the only mammalian 1-Cys member of the peroxiredoxin superfamily and is expressed in all major organs, with a particularly high level in lung. Prdx6 uses GSH as an electron donor to reduce H2O2 and other hydroperoxides including phospholipid hydroperoxides at approximately 5 micromol/mg protein/min with K1 approximately 3 x 10(6) M(-1) s(-1). Oxidation of the Cys47 to a sulfenic acid during catalysis requires piGST-catalyzed glutathionylation and reduction with GSH to complete the enzymatic cycle. Prdx6 stably overexpressed in cells protected against oxidative stress, whereas antisense treatment resulted in oxidant stress and apoptosis. Adenoviral-mediated overexpression of Prdx6 in mouse lungs protected against the toxicity of hyperoxia, whereas Prdx6-null mice were more sensitive to the effects of hyperoxia or paraquat. We postulate that Prdx6 functions in antioxidant defense mainly by facilitating repair of damaged cell membranes via reduction of peroxidized phospholipids. The PLA2 activity of Prdx6 is Ca2+ independent and maximal at acidic pH. Inhibition of PLA2 activity results in alterations of lung surfactant phospholipid synthesis and turnover. Thus, Prdx6, a unique mammalian peroxiredoxin, is an important antioxidant enzyme and has a major role in lung phospholipid metabolism.
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PMID:Peroxiredoxin 6, a 1-Cys peroxiredoxin, functions in antioxidant defense and lung phospholipid metabolism. 1589 Jun 16

Peroxiredoxin 6 (Prd x 6) is a novel peroxidase enzyme that is expressed at a high level in the lung. We tested the hypothesis that transgenic (Tg) mice overexpressing Prd x 6 would exhibit increased resistance to hyperoxia-induced lung injury. Wild-type and Tg mice were exposed to 100% O(2) and evaluated for survival, lung histopathology, total protein, and nucleated cells in bronchoalveolar lavage fluid (BALF), and oxidation of lung protein and lipids. Prd x 6 protein expression and enzyme activity were approximately 3-fold higher in Tg lungs compared with wild-type. Tg mice survived longer during exposure to 100% O(2) (LT(50) 104+/-2.8 h in Tg versus 88.9+/-1.1 h for wild-type). Lung wet/dry weight ratio and total protein and nucleated cell count in lung lavage fluid were significantly greater in wild-type mice at 72 and 96 h of hyperoxia compared with Tg mice. At 96 h of hyperoxia, Tg mice had less epithelial cell necrosis, perivascular edema, and inflammatory cell recruitment by light microscopy, and lower TBARS and protein carbonyls in lung homogenate (P<0.05). These results show that Tg mice have increased defense against lung injury in hyperoxia, providing evidence that Prd x 6 functions as a lung antioxidant enzyme.
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PMID:Transgenic mice overexpressing peroxiredoxin 6 show increased resistance to lung injury in hyperoxia. 1639 55

Mice with knock-out of peroxiredoxin 6 (Prdx6), a recently described antioxidant enzyme, were evaluated for susceptibility to lung injury with paraquat (PQ) administration. With high dose PQ (30 mg/kg i.p.), all Prdx6-/- mice died (LT50 54 +/- 2.05 h, mean +/- SE) by 4 days, whereas 86% of the wild-type (WT) mice (C57BL/6) survived (n = 14). At 2 days after PQ, lung wet/dry weight ratio increased significantly (p < 0.05) to 7.57 +/- 0.37 in Prdx6-/- mice vs. 5.42 +/- 0.25 in WT mice. Total protein and nucleated cells in bronchoalveolar lavage fluid and TBARS and protein carbonyls in lung homogenate also showed more marked increases in Prdx6-/- mice. At 2.5 days after PQ, light microscopy of WT lungs showed mild injury while Prdx6-/- lungs showed epithelial cell necrosis, perivascular edema, and inflammatory cells. With low dose PQ (12.5 mg/kg), mortality and lung injury were less marked but were significantly greater with Prdx6-/- compared to WT mice. These results show that Prdx6-/- mice have increased susceptibility to lung injury with PQ administration. Thus, Prdx6 protects lungs against PQ toxicity as shown previously for hyperoxia, indicating that it functions as an important lung antioxidant enzyme.
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PMID:Peroxiredoxin 6 gene-targeted mice show increased lung injury with paraquat-induced oxidative stress. 1648 56

The aim was to study the effects of a scuba diving session on the lymphocyte antioxidant system, NO synthesis, the capability to produce reactive oxygen species and the antioxidant response in neutrophils. For that purpose seven male divers performed an immersion at a depth of 40 m for 25 min. The same parameters were measured after an hyperbaric oxygen (HBO) treatment at resting conditions in a hyperbaric chamber. Lymphocyte H2O2 production rose after diving and after HBO treatment. Glutathione peroxidase (GPx) and catalase activities increased after diving in lymphocytes, while after HBO exposure only increased GPx activity. Lymphocyte HO-1 mRNA expression increased after diving and after HBO exposure, while iNOS levels and nitrite levels significantly increased after diving. The hyperoxia associated to scuba diving leads to a condition of oxidative stress with increased lymphocyte H2O2 production, HO-1 expression, NO synthesis and antioxidant enzyme adaptations in order to avoid oxidative damage.
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PMID:Scuba diving enhances endogenous antioxidant defenses in lymphocytes and neutrophils. 1736 55

The deleterious effects of oxidants on proteins may be modified by overexpression of uncoupling protein 3 (UCP3) in skeletal muscle cells exposed to hyperoxia or H(2)O(2). UCP3 overexpression significantly attenuated the increase in protein carbonylation in response to hyperoxia and H(2)O(2) exposures. However, antioxidant enzyme content and activity (superoxide dismutases, peroxiredoxins, glutathione peroxidase-I, and catalase) were reduced or not modified in UCP3-overexpressing myotubes exposed to oxidants. Protein nitration increased in UCP3-overexpressing cells exposed to hyperoxia, but not to H(2)O(2). We conclude that protein oxidation rather than nitration is neutralized by UPC3 overexpression in mouse myotubes exposed to abundant reactive oxygen species.
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PMID:UCP3 overexpression neutralizes oxidative stress rather than nitrosative stress in mouse myotubes. 1910 52

Recent studies suggest that intermittent and prolonged normobaric hyperoxia results in ischemic tolerance to reduce ischemia brain injury. In this research attempts were made to see the changes in antioxidant enzyme activities following prolonged and intermittent normobaric hyperoxia preconditioning. Rats were divided into four experimental groups, each of 21 animals. The first two were exposed to 95% inspired normobaric hyperoxia for 4 h/day for 6 consecutive days (intermittent normobaric hyperoxia) or for 24 h continuous (prolonged normobaric hyperoxia). The second two groups acted as controls, and were exposed to 21% oxygen in the same chamber. Each main group was subdivided to middle cerebral artery occlusion-operated, sham-operated (without middle cerebral artery occlusion), and intact (without any surgery) subgroups. After 24 h, middle cerebral artery occlusion-operated subgroups were subjected to 60 min of right middle cerebral artery occlusion. After 24 h reperfusion, neurologic deficit score, infarct volume were measured in middle cerebral artery occlusion-operated subgroups. Antioxidant enzyme activities were assessed in sham-operated and intact subgroups. Preconditioning with prolonged and intermittent normobaric hyperoxia decreased neurologic deficit score and infarct volume, and increased antioxidant enzyme activities (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase) significantly. Although further studies are needed to clarify the mechanisms of ischemic tolerance, the intermittent and prolonged normobaric hyperoxia seems to partly exert their effects via increase antioxidant enzymes activities.
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PMID:In vivo normobaric hyperoxia preconditioning induces different degrees of antioxidant enzymes activities in rat brain tissue. 1930 5

Nuclear factor-erythroid 2 related factor 2 (Nrf2) is a ubiquitous master transcription factor that regulates antioxidant response elements (AREs)-mediated expression of antioxidant enzyme and cytoprotective proteins. In the unstressed condition, Kelch-like ECH-associated protein 1 (Keap1) suppresses cellular Nrf2 in cytoplasm and drives its proteasomal degradation. Nrf2 can be activated by diverse stimuli including oxidants, pro-oxidants, antioxidants, and chemopreventive agents. Nrf2 induces cellular rescue pathways against oxidative injury, abnormal inflammatory and immune responses, apoptosis, and carcinogenesis. Application of Nrf2 germ-line mutant mice has identified an extensive range of protective roles for Nrf2 in experimental models of human disorders in the liver, gastrointestinal tract, airway, kidney, brain, circulation, and immune or nerve system. In the lung, lack of Nrf2 exacerbated toxicity caused by multiple oxidative insults including supplemental respiratory therapy (e.g., hyperoxia, mechanical ventilation), cigarette smoke, allergen, virus, bacterial endotoxin and other inflammatory agents (e.g., carrageenin), environmental pollution (e.g., particles), and a fibrotic agent bleomycin. Microarray analyses and bioinformatic studies elucidated functional AREs and Nrf2-directed genes that are critical components of signaling mechanisms in pulmonary protection by Nrf2. Association of loss of function with promoter polymorphisms in NRF2 or somatic and epigenetic mutations in KEAP1 and NRF2 has been found in cohorts of patients with acute lung injury/acute respiratory distress syndrome or lung cancer, which further supports the role for NRF2 in these lung diseases. In the current review, we address the role of Nrf2 in airways based on emerging evidence from experimental oxidative disease models and human studies.
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PMID:Nrf2 protects against airway disorders. 1964 63


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