Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A rise of hemoglobin concentration accompanied by an increase of the total iron in the blood serum of white mice was found under oxygen pressure of 4 atm for an hour (preconvulsive state) and 6 atm (convulsive state). Changes in correlations of hemoglobin fractions in the blood serum were detected in both stages of oxygen poisoning by disc-electrophoresis in 7.5% polyacrylamide gel. A rise of transferrin concentration under these conditions (hyperoxia) was observed. The deflections occurred were less pronounced following administration of urea to the animals before hyperbaric oxygenation.
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PMID:[Hemoglobin, transferrin and total iron content in the blood serum in hyperoxia and during the protective action of urea]. 46 81

To study the early changes in the lower respiratory tract in persons exposed to periods of hyperoxia usually considered safe, we evaluated 14 normal subjects by bronchoalveolar lavage before and immediately after 16.7 +/- 1.1 hours of breathing more than 95 per cent oxygen. Hyperoxia caused a significant alveolar-capillary "leak" as detected by the presence of increased plasma albumin and transferrin in lavage fluid. These changes were reversible, as shown at repeat lavage in four subjects two weeks after oxygen administration. Hyperoxia for an average of 17 hours did not change the total number or type of lung inflammatory and immune effector cells recovered by lavage (P greater than 0.05, all comparisons). However, alveolar macrophages from subjects exposed to oxygen released increased amounts of fibronectin (P less than 0.05) and alveolar-macrophage--derived growth factor for fibroblasts (P less than 0.01)--mediators thought to modulate fibroblast recruitment and proliferation in the alveolar wall. Thus, although some of the effects of exposure to 17 hours of more than 95 per cent oxygen are reversible, hyperoxia for even this short period lowers the structural or functional barriers that normally prevent alveolar-capillary "leak" and induces processes that can culminate in fibrosis of the alveolar wall.
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PMID:Pulmonary oxygen toxicity. Early reversible changes in human alveolar structures induced by hyperoxia. 688 81

Proteins that decrease the surface activity of surfactant accumulate in epithelial lining fluid in respiratory failure. The aim of this study was to isolate a surfactant inhibitor from the airways of rabbits in acute respiratory failure induced by bronchoalveolar lavage (BAL). This inhibitor was identified as being transferrin (TF). Unlike serum TF, TF recovered in respiratory failure was saturated with iron (Fe(3+)-TF). Fe(3+)-TF decreased the surface activity of normal surfactant in vitro, whereas iron-free TF had no effect. In the presence of H2O2 and a reducing agent, Fe(+3)-TF inactivated the surfactant complex: the surface absorption rate was decreased, immunoreactive surfactant protein A was decreased, and malondialdehyde was formed. The acute effects of Fe(3+)-TF and iron-free TF applied to the airways were studied in animal models. In respiratory failure induced by BAL, Fe(3+)-TF deteriorated respiratory failure, whereas iron-free TF had no effect. In respiratory failure induced by hyperoxia for 48 h, administration of iron-free TF ameliorated the respiratory failure and improved the surface activity in BAL. We propose that Fe(3+)-TF accumulating in epithelial lining fluid during lung damage contributes to surfactant inhibition and promotes the formation of free radicals that inactivate the surfactant system.
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PMID:Interaction of transferrin saturated with iron with lung surfactant in respiratory failure. 800 25

To study whether nitric oxide (NO) affects surfactant function, 36 young rats inhaled one of the following humidified environments for 24 h: 1) air; 2) 95% O2; 3) air and 100 parts/million (ppm) NO; and 4) 95% O2 and 100 ppm NO. The treatments did not change the recovery of phospholipid from bronchoalveolar lavage (BAL). Exposure to NO of animals that breathed either air or 95% O2 increased the minimum surface tension of surfactant from BAL at low (1.5 mumol/ml), but not at high (4 mumol/ml), phosphatidylcholine concentration. After inhaled NO, the nonsedimentable protein of BAL decreased the surface activity of surfactant (1 mumol phosphatidylcholine/ml) more than the protein from the controls. NO treatment of animals that breathed either air or 95% O2 affected neither the quantity nor the molecular weight distribution of nonsedimentable protein. Hyperoxia increased the amount of the nonsedimentable protein, whereas NO increased the iron saturation of transferrin. The surfactant fraction and the nonsedimentable protein from BAL were separately exposed to 80 ppm NO in vitro. NO exposure had no effect on the surface activity of surfactant fraction. NO exposure of nonsedimentable protein from the control animals (no NO) increased the inhibition of the surface activity and changed the adsorption spectrum of the protein, suggesting conversion of hemoglobin to methemoglobin. Nonsedimentable protein from NO-exposed animals contained methemoglobin. We propose that surfactant dysfunction caused by inhaled NO is in part due to alteration of protein(s) in epithelial lining fluid that in turn inactivates surfactant.
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PMID:Surfactant dysfunction after inhalation of nitric oxide. 880 10

In respiratory failure, transferrin (TF) with variable iron saturation accumulates in the alveolar space. Binding free iron to TF may inhibit metal-catalyzed formation of free radicals. The aim of this study was to evaluate whether the degree of the iron-saturation of TF influences the severity of respiratory failure and surfactant responsiveness. Surfactant deficiency and lung edema was induced in 42 paralyzed and ventilated young rabbits by bronchoalveolar lavage (BAL); 19 of these animals were preexposed to 100% O2 for 40 hours. The animals received (1) exogenous surfactant intratracheally (100 mg/kg in 4 ml/kg saline); (2) surfactant and Fe(3+)-TF (50 or 25 mg/kg); or (3) surfactant and iron-free TF (50 mg/kg). One hour after administration of TF, 13-25% of exogenous TF was recovered by BAL. Administration of Iron-free TF significantly decreased the iron saturation of TF in BAL. In acute respiratory failure induced by BAL, Fe(3+)-TF decreased the efficacy of exogenous surfactant in improving the gas exchange, and increased surfactant inhibition, while iron-free TF had no effect. By contrast, in respiratory failure induced by hyperoxia and BAL, iron-free TF improved the efficacy of exogenous surfactant, but Fe(2+)-TF had no effect. After administration of iron-free TF, surfactant isolated from BAL was more surface-active than surfactant from BAL of the other hyperoxia-treated animals. In animals exposed to hyperoxia, treatment with iron-free TF decreased malondialdehyde content of BAL. We propose that low iron saturation of TF decreases oxidant stress and favors the recovery from respiratory failure.
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PMID:Transferrin modifies surfactant responsiveness in acute respiratory failure: role of iron-free transferrin as an antioxidant. 885 99

Iron is an important catalyst for free oxygen radicals and lipid peroxidation reactions which may play a role in the pathogenesis of several diseases in premature infants. During the early neonatal period, extracellular iron is available in excessive amounts. We hypothesized that administration of erythropoietin (EPO) mobilizes iron from plasma and inhibits iron-catalyzed reactions. To evaluate this hypothesis, recombinant human EPO (rhEPO) was administered s.c. to premature rabbits delivered at 29-d gestation: one group was kept in room air (RA) and the other in a 100% oxygen environment. Within each group, the animals were randomized to receive placebo or rhEPO at 400 or at 800 U/kg on d 0 and 2 of life. On d 3 or 4, plasma iron and iron saturation of transferrin were assessed. Lipid peroxidation was analyzed in plasma and bronchoalveolar lavage fluid (BAL). Nonsedimentable protein (NSP) and phospholipid content were measured in BAL. Erythropoiesis was evaluated in liver and bone marrow. Treatment with rhEPO decreased plasma iron, decreased iron saturation of transferrin, increased reticulocytes, and increased erythropoiesis in liver and bone marrow in both RA and hyperoxia group. Oxygen exposure increased NSP in BAL and decreased the ability of BAL to inhibit lipid peroxidation as measured by malondialdehyde (MDA) generation compared with RA exposure. In O2-exposed animals, EPO treatment increased the ability of both plasma (EPO 800) and BAL (EPO 400 and 800) to inhibit lipid peroxidation and decreased NSP in BAL (EPO 400). In addition, rhEPO treatment decreased alveolar thickening and proteinaceous exudate in the hyperoxia group. We propose that by stimulating erythropoiesis, rhEPO mobilizes non-heme iron and decreases oxidant injury that depends on the availability of transient metal.
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PMID:Recombinant human erythropoietin: possible role as an antioxidant in premature rabbits. 886 72

The hypotransferrinemic mouse (trf (hpx)) is a mutant strain exhibiting transferrin deficiency, marked anemia, hyperabsorption of iron, and elevated hepatic iron stores. We set out to investigate the relative roles of anemia and of transferrin in the malregulation of intestinal iron absorption in these animals. Transfusion of erythrocytes obtained from littermate controls increased hemoglobin levels and reduced reticulocyte counts in recipient animals. Although mucosal to carcass (59)Fe transfer was reduced, total duodenal iron uptake was not significantly affected. Iron absorption in homozygotes, in contrast to littermate controls, was not reduced by hyperoxia. Mouse transferrin injections, in the short term, increased delivery of iron to the marrow and raised hemoglobin levels. Although mucosal transfer and total iron uptake were reduced at the higher transferrin doses, total uptake was still higher than in controls. Daily injections of mouse/human transferrin for 3 weeks from weaning, normalized hemoglobin values, and markedly reduced liver iron and intestinal iron absorption values in trf (hpx) animals. When such daily-injected mice were left for a week to allow transferrin clearance, iron absorption values were significantly enhanced; hemoglobin or hepatic iron levels were, however, not significantly altered. These data indicate that hyperabsorption of iron in trf (hpx) mice is not solely because of the anemia; transferrin levels per se do affect iron absorption, possibly via a direct effect on the intestinal mucosa.
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PMID:Importance of anemia and transferrin levels in the regulation of intestinal iron absorption in hypotransferrinemic mice. 1055 6

The major function of the erythrocyte is to transport oxygen from the lungs to the other tissues, a function ensured by the glycoprotein hormone erythropoietin which couples red cell production to long term tissue oxygen requirements. Tissue hypoxia is the only physiological mechanism for increasing erythropoietin production but there are a variety of mechanisms for its down regulation including hyperoxia, increased catabolism by an expanded erythroid progenitor cell pool, blood hyperviscosity independently of its oxygen content, renal disease and the cytokines produced in inflammatory, infectious and neoplastic disorders. Erythropoietin lack results in severe and often transfusion-dependent anemia but if bone marrow function is otherwise normal, recombinant human erythropoietin therapy can restore the red cell mass and alleviate the transfusion need. However, elevation of the red cell mass by recombinant human erythropoietin is associated with a reduction in plasma volume and in some patients, hypertension is induced. Elevation of the red cell mass is also associated with a reduction in cerebral blood flow. When used to gradually elevate the hematocrit to 36% in anemic patients, recombinant human erythropoietin therapy is usually uneventful. However, when the normal hematocrit level is exceeded, the risk for thrombotic events increases since blood viscosity varies exponentially with the hematocrit. Increasing the hematocrit by autologous blood transfusions can enhance athletic performance in fit individuals and recombinant human erythropoietin administration is an obvious surrogate for autologous blood transfusions. However, paradoxically, its effects are the opposite of those of endurance training, namely a change in red cell mass without an increase in the total blood volume. Thus, the use of recombinant human erythropoietin as a performance-enhancing agent is dangerous, particularly in the less fit athlete, and probably of little benefit in the highly conditioned one. Differences in the carbohydrate content of native and recombinant human erythropoietin are identifiable by isoelectric focusing, providing a direct means for detecting erythropoietin abuse using urine specimens; a panel of surrogate blood markers of enhanced erythropoiesis such as soluble transferrin receptors, serum erythropoietin, reticulocyte hematocrit and percent macrocytes provide an indirect means for this purpose. Timing of surveillance is, of course, critical due to biological limitations on the physical presence of the hormone. However, education about its dangers may prove to be the most valuable solution to abuse of recombinant human erythropoietin for competitive advantage.
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PMID:Erythropoietin use and abuse: When physiology and pharmacology collide. 1195 Jan 39

High inspired concentrations of oxygen (hyperoxia) are often necessary to counteract tissue hypoxia during the treatment of ARDS. Reactive oxygen species generated by hyperoxic therapy may influence the expression of the pulmonary proteome and the application of discovery proteomics to the hyperoxic lung has the potential to divulge mechanisms regulating the expression of specific proteins integral to lung injury and repair. The present study examined the proteome derived from 30-day-old Sprague-Dawley rats exposed to room air (RA) and 95% O2 (Ox) for 24-72 hours using 2-dimensional difference in-gel electrophoresis (2D-DIGE) coupled with MALDI-ToF/ToF mass spectrometry. A total of 870 protein spots were visualized by 2D-DIGE across all gels. Mass spectral analysis identified 51 proteins representing 187 of the 214 significantly altered spots. Molecular and cellular function analysis grouped the identified proteins into free radical scavenging, cell death, cell-to-cell signaling, and cellular movement categories. The majority of the differences in the protein spots between RA and Ox occurred at 72 hours, with albumin, annexin A6 (AnxA6), and transferrin being increased, and mitochondrial Lon peptidase 1 being decreased by at least 20%. In Ox animals, AnxA6 protein expression increased three-fold without an increase in mRNA expression. Bioinformatic analysis of the AnxA6 transcript revealed the presence of a putative internal ribosome entry site within the 5'-untranslated region. These findings indicate that hyperoxia induces significant alterations in the pulmonary proteome which are temporally related. In addition, hyperoxia selectively enhances the expression of some proteins whose transcripts contain sequence motifs, which impart translational regulation.
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PMID:Hyperoxia-induced alterations in the pulmonary proteome of juvenile rats. 2336 26

Evidence that mitochondrial dysfunction plays a central role in drug-induced liver injury is rapidly accumulating. In contrast to physiological conditions, in which almost all adenosine triphosphate (ATP) in hepatocytes is generated in mitochondria via aerobic respiration, the high glucose content and limited oxygen supply of conventional culture systems force primary hepatocytes to generate most ATP via cytosolic glycolysis. Thus, such anaerobically poised cells are resistant to xenobiotics that impair mitochondrial function, and are not suitable to identify drugs with mitochondrial liabilities. In this study, primary rat hepatocytes were cultured in galactose-based medium, instead of the conventional glucose-based medium, and in hyperoxia to improve the reliance of energy generation on aerobic respiration. Activation of mitochondria was verified by diminished cellular lactate release and increased oxygen consumption. These conditions improved sensitivity to the mitochondrial complex I inhibitor rotenone. Since oxidative stress is also a general cause of mitochondrial impairment, cells were exposed to test compounds in the presence of transferrin to increase the generation of reactive oxygen species via increased uptake of iron. Finally, 14 compounds with reported mitochondrial liabilities were tested to validate this new drug-induced mitochondrial toxicity assay. Overall, the culture of primary rat hepatocytes in galactose, hyperoxia and transferrin is a useful model for the identification of mitochondrial dysfunction-related drug-induced hepatotoxicity.
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PMID:Assessment of mitochondrial dysfunction-related, drug-induced hepatotoxicity in primary rat hepatocytes. 2709 95


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