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

The generation of reactive oxygen species (ROS) is a steady-state cellular event in respiring cells. Their production can be grossly amplified in response to a variety of pathophysiological conditions such as inflammation, immunologic disorders, hypoxia, hyperoxia, metabolism of drug or alcohol, exposure to UV or therapeutic radiation, and deficiency in antioxidant vitamins. Uncontrolled production of ROS often leads to damage of cellular macromolecules (DNA, protein, and lipids) and other small antioxidant molecules. A number of major cellular defense mechanisms exist to neutralize and combat the damaging effects of these reactive substances. The enzymic system functions by direct or sequential removal of ROS (superoxide dismutase, catalase, and glutathione peroxidase), thereby terminating their activities. Metal binding proteins, targeted to bind iron and copper ions, ensure that these Fenton metals are cryptic. Nonenzymic defense consists of scavenging molecules that are endogenously produced (GSH, ubiquinols, uric acid) or those derived from the diet (vitamins C and E, lipoic acid, selenium, riboflavin, zinc, and the carotenoids). These antioxidant nutrients occupy distinct cellular compartments and among them, there are active recycling. For example, oxidized vitamin E (tocopheroxy radical) has been shown to be regenerated by ascorbate, GSH, lipoic acid, or ubiquinols. GSH disulfides (GSSG) can be regenerated by GSSG reductase (a riboflavin-dependent protein), and enzymic pathways have been identified for the recycling of ascorbate radical and dehydroascorbate. The electrons that are used to fuel these recycling reactions (NADH and NADPH) are ultimately derived from the oxidation of foods. Sickle cell anemia, thalassemia, and glucose-6-phosphate-dehydrogenase deficiency are all hereditary disorders with higher potential for oxidative damage due to chronic redox imbalance in red cells that often results in clinical manifestation of mild to serve hemolysis in patients with these disorders. The release of hemoglobin during hemolysis and the subsequent therapeutic transfusion in some cases lead to systemic iron overloading that further potentiates the generation of ROS. Antioxidant status in anemia will be examined, and the potential application of antioxidant treatment as an adjunct therapy under these conditions will be discussed.
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PMID:Interaction of antioxidants and their implication in genetic anemia. 1060 86

Periventricular leukomalacia (PVL) is the main cause of neurological impairment in premature newborns. The pathogenesis of PVL remains unclear but may involve glutamate excitotoxicity and free radical production. Oxygen and iron, which are widely used in premature newborns, are oxidizing agents with a potential for promoting free radical production. We previously described a mouse model of excitotoxic neonatal white matter lesions mimicking several aspects of human PVL. In the present study, we used this mouse model to investigate whether iron pretreatment or 100% oxygen exposure worsened excitotoxic lesions. We found that iron pretreatment but not hyperoxia significantly increased white matter lesions, suggesting that high doses of iron may aggravate PVL in premature newborns.
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PMID:Iron supplementation aggravates periventricular cystic white matter lesions in newborn mice. 1072 98

Oxygen radicals are considered to be major causative factors in many illnesses of preterm infants. This article reviews the antioxidant defenses in immature animals and preterm infants, and attempts to quantitate their vulnerabilities to oxidants. Sources of oxidants, including hyperoxia, iron, parenteral nutrition, nitric oxide, and prooxidants, and their impact on immature antioxidant defenses are discussed. Genetic manipulations of antioxidant enzymes such as knockout and transgenic mice models are reviewed. The various clinical and investigational antioxidant therapies in animals and humans and difficulties in the design of antioxidant therapy studies are explored.
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PMID:The precarious antioxidant defenses of the preterm infant. 1104 38

Ferritin is an intracellular iron storage protein and its translation is inhibited by binding of iron regulatory proteins (IRPs) to the iron-responsive element (IRE) located in the 5' untranslated region of its mRNA. In this paper, we have investigated the effect of hyperoxia and iron on the binding activity of IRP-1 and the ferritin synthesis in mouse peritoneal macrophages. The binding activity of IRP-1 was increased and the ferritin synthesis was suppressed when the macrophages were cultured under hyperoxia, and the reverse occurred under hypoxia. Iron diminished the IRP-1-binding activity and the enhanced synthesis of ferritin. However, this effect was arrested under hyperoxia. Consistently, hypoxia-induced loss of binding activity of IRP-1 and the enhanced synthesis of ferritin were blocked in the presence of an iron chelator deferoxamine. These alterations of the binding activity of IRP-1 in response to oxygen and iron were not reproduced in the cell-free extract. The data suggest that in the macrophages oxygen and iron inversely act on the binding activity of IRP-1 and the ferritin synthesis, and that intracellular mechanism(s) to sense iron and/or oxygen is required for these actions.
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PMID:Effects of hyperoxia and iron on iron regulatory protein-1 activity and the ferritin synthesis in mouse peritoneal macrophages. 1134 46

Ceruloplasmin, metallothionein, and ferritin are metal-binding proteins with potential antioxidant activity. Despite evidence that they are upregulated in pulmonary tissue after oxidative stress, little is known regarding their influence on trace metal homeostasis. In this study, we have used copper- and zinc-containing superoxide dismutase (Cu/Zn SOD) transgenic-overexpressing and gene knockout mice and hyperoxia to investigate the effects of chronic and acute oxidative stress on the expression of these metalloproteins and to identify their influence on copper, zinc, and iron homeostasis. We found that the oxidative stress-mediated induction of ceruloplasmin and metallothionein in the lung had no effect on tissue levels of copper, iron, or zinc. However, Cu/Zn SOD expression had a marked influence on hepatic copper and iron as well as circulating copper homeostasis. These results suggest that ceruloplasmin and metallothionein may function as antioxidants independent of their role in trace metal homeostasis and that Cu/Zn SOD functions in copper homeostasis via mechanisms distinct from its superoxide scavenging properties.
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PMID:Cellular response of antioxidant metalloproteins in Cu/Zn SOD transgenic mice exposed to hyperoxia. 1140 60

A reduction in hemoglobin concentration has been consistently reported after deep saturation dives, whereas reductions in thrombocyte counts and changes in biochemical parameters specific for liver function have been reported after some dives. In this study the contribution of exposure to hyperoxia to these changes were studied. Hemoglobin concentration, blood cell counts, serum ferritin, and biochemical parameters specific for liver damage were measured before and after a shallow 28-day saturation dive to a pressure of 250 kPa with the same hyperoxic exposure (40-50 kPa) as in a deep saturation dive in eight male divers. The same parameters were measured before, during, and after a standard 21-day hyperbaric oxygen (HBO2) treatment series in a selected group of 16 patients (8 male). There were significant reductions in hemoglobin concentrations of 3.8 +/- 4.7% (P = 0.023) and 10.2 +/- 5.3% (P = 0.003) after the HBO2 treatment series and dive, respectively, accompanied with reductions in red cell counts, reticulocyte counts, and hematocrit. There was an increase in ferritin concentrations of 29 +/- 21% (P = 0.002) and 107 +/- 43% (P < 0.001). In contrast to some deep dives, there were no changes in thrombocyte counts or biochemical parameters specific for liver damage. Exposure to hyperoxia contributes significantly to reduced hemoglobin and increased ferritin concentrations after saturation dives. The changes may reflect a shift of iron from synthesis of hemoglobin in the bone marrow to storage in macrophages caused by a downregulation of hemoglobin synthesis, or an increased oxidative stress. The changes are too small to be of clinical significance with respect to diving and HBO2 treatment.
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PMID:Exposure to hyperoxia in diving and hyperbaric medicine--effects on blood cell counts and serum ferritin. 1190 96

The effects of intracellular pH (pH(i)), paramagnetic macroscopic, and microscopic susceptibility on T(1) in the rotating frame (T(1rho)) were studied in rat brain. Intracellular acidosis was induced by hypercapnia and pH(i), T(1rho), T(2), diffusion, and cerebral blood volume (CBV) were quantified. Taking into account the CBV contribution, a prolongation of parenchymal T(1rho) by 4.5% was ascribed to a change in tissue water relaxation caused by a one unit drop in pH(i). Blood T(1rho) was found to prolong linearly with blood oxygenation saturation (Y). The macroscopic susceptibility contribution to parenchymal T(1rho) was assessed both through BOLD and an iron oxide contrast agent, AMI-227. The T(1rho) data from these experiments could be described by intravascular effects with insignificant effects of susceptibility gradients on tissue water. Tissue oxygen tension (PtO(2)) was manipulated and monitored with microelectrodes to assess its plausible contribution to microscopic susceptibility and relaxation. Parenchymal T(1rho) was virtually unaffected by variations in the PtO(2), but T(1) was shortened in hyperoxia and T(2) showed a negative BOLD effect in hypoxia. It is demonstrated that pH(i) directly modulates tissue T(1rho), possibly through its effect on proton exchange; however, neither BOLD nor PtO(2) directly influence tissue T(1rho). The observations are discussed in the light of physicochemical mechanisms contributing to the ischemic T(1rho) changes.
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PMID:Effects of intracellular pH, blood, and tissue oxygen tension on T1rho relaxation in rat brain. 1221 Sep 11

In many models, a protective role for heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme degradation, has been demonstrated. Also, HO-1 null mice (KO) are more susceptible to inflammation and hypoxia and transplant rejection. Nonetheless, their response to hyperoxia (> 95% O(2)) has not yet been evaluated. Surprisingly, after acute hyperoxic exposure, KO had significantly decreased markers of lung oxidative injury and survived chronic hyperoxia as well as wild-type (WT) controls. Disrupted HO-1 expression was associated with decreased lung reactive iron and iron-associated proteins, decreased NADPH cytochrome cp450 reductase activity, and decreased lung peroxidase activity compared to WT. Injection of tin protoporphyrin, an inhibitor of HO, in the WT decreased acute hyperoxic lung injury, whereas transduction of human HO-1 in the KO reversed the relative protection of the KO to acute injury and worsened hyperoxic survival. This suggests that disruption of HO-1 protects against hyperoxia by diminishing the generation of toxic reactive intermediates in the lung via iron and H(2)O(2).
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PMID:Resistance to hyperoxia with heme oxygenase-1 disruption: role of iron. 1249 87

There is increasing evidence that oxidative stress is implicated in the development of bronchopulmonary dysplasia. Several important factors contribute to augmented oxidative stress in the newborn and especially the preterm infant: first, because of its immaturity, the lung of preterm infants is frequently exposed to oxygen therapy and hyperoxia. Second, the antioxidant defense and its ability to be induced during an hyperoxic challenge are impaired. Third, the preterm infant has an increased susceptibility to infection and inflammation, which increases oxidative stress. Fourth, free iron, which catalyzes the production of toxic reactive oxygen species, can be detected in preterm infants. The molecular and cellular mechanisms for free radical-induced injury are now understood in more detail, and it is clear that oxidative stress plays an important role in triggering apoptosis, in serving as second messenger and in signal transduction. This new insight might lead to novel and efficient therapies. So far, there has been no significant breakthrough regarding antioxidant therapies. Care should, however, be exercised in supplementing the preterm infant with antioxidants since this may affect growth and development.
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PMID:Bronchopulmonary dysplasia-oxidative stress and antioxidants. 1266 29

Current evidence suggests that a modulatory action on O(2)-dependent EPO secretion is exerted by the erythroid/precursor cell population in the erythropoietic organs through a negative feedback system. The hypothesis is based on studies of stimulated-EPO secretion performed in mice in whom the erythropoietic rates were either enhanced or depressed in the presence of normal plasma EPO half-lives. Since erythropoietic depression was elicited by cyclophosphamide administration, which could have altered EPO production directly, the aim of the present investigation was to estimate hypoxia-stimulated EPO secretion in a mouse model of functional depressed erythropoiesis induced by exposure to normobaric hyperoxia. Females CF#1 mice aged 70 d were divided into control (C) and experimental (E) groups. The former was maintained in plastic cages in a normal environment, while the latter was placed in an environment of 60% O(2)/40% N(2) in an 85-dm(3) atmospheric chamber with air flow of 1 L/min. Erythropoiesis was evaluated by either 24-h RBC-(59)Fe uptake or iron kinetics performed 3 h after IV injection of a tracer dose of (59)Fe. Both indexes of the red cell production rate were significantly depressed in E mice. Plasma disappearance of exogenous EPO in C mice, as well as in E mice exposed to hyperoxia for 4 d, was estimated by injecting (125)I-rHuEPO intravenously. Linear regression analysis indicated that neither the differences between the slopes of both curves nor the Y-intercepts were significant. Hypobaric hypoxemia was used as stimulus for EPO production. Plasma immuno-EPO titer after a 4-h exposure to hypobaric air was 73% higher in mice with hyperoxia-induced hypoerythropoiesis than in control mice with normal erythropoiesis. Data support the concept that the rate of erythropoiesis, perhaps through the number of the erythroid progenitor/precursor cell population, modulates O(2)-dependent EPO secretion.
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PMID:Enhanced hypoxia-stimulated erythropoietin production in mice with depression of erythropoiesis induced by hyperoxia. 1271 14


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