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

In order to investigate the effects of high concentrations of oxygen on the lung, experiments were performed on 18 baboons exposed to a humidified environment of 95% oxygen for five days. Open lung biopsies for biochemical assay, histologic and electron microscopic analysis and measurement of tissue respiration were performed before and after oxygen exposure. Pulmonary function was evaluated by measurement of arterial blood gases, compliance, closing capacity (CC), functional residual capacity (FRC), total lung capacity (TLC), residual volume (RV) and vital capacity (VC) before and after exposure and then at seven and 14 days in the animals which recovered. Six baboons removed from the oxygen environment after 96--110 hours and exposed to room air died within three to 20 hours of profound hypoxemia (PaO2 40 +/- 6). The remaining 12 baboons were successfully weaned to room air over a three day period with a return of ABGs to control values (PaO2 89+/- 2). Electron microscopic analysis of alveolar membranes exposed to 120 hours of hyperoxia demonstrated endothelial cell swelling, interstitial alveolar membrane edema, and an increased predominance of Type II pneumocytes. Lung volume measurements showed significant decreases in TLC (25%), VC (34%), CC/TLC (28%) and dynamic compliance (47%). Biochemical studies indicated a shift toward anaerobic metabolism with a decrese in tissue oxygen consumption, reduced cytochrome oxidase activity, and increased lung lactic acid production. These changes were all found to be reversible in the 12 baboons slowly weaned back to room air.
 ...
PMID:Reversible pulmonary oxygen toxicity in the primate. 21 38

O2-mediated alterations in cell energy metabolism may play a role in structural and functional abnormalities described in type II pneumocytes (T-II-P) following in vivo hyperoxia. Bioenergetic alterations produced by hyperoxia (95% O2) were therefore examined in a culture-maintained cell line derived from T-II-P. Exposure of cell monolayers to 95% O2 for 96 h results in a significant decrease in O2 consumption (from 0.52 +/- 0.07 to 0.30 +/- 0.08, P less than 0.01), suggesting impaired mitochondrial energy provision. In addition, there are increased rates of aerobic lactate production (from 2.89 +/- 0.52 to 3.84 +/-0.80, P less than 0.05) with loss of Pasteur effect, indicating a shift to glycolytic metabolism at relatively high PO2's. These metabolic changes are not accompanied by altered activities of critical mitochondrial (cytochrome oxidase) or glycolytic (pyruvate kinase, phosphofructokinase) enzymes. Altered cell bioenergetics following hyperoxia may this represent an important secondary mechanism leading to functional abnormalities in T-II-P.
 ...
PMID:Effects of high oxygen exposure on bioenergetics in isolated type II pneumocytes. 22 21

Previous work has shown that irrespective of the route of exposure methyl isocyanate (MIC) caused acute lactic acidosis in rats (Jeevaratnam et al., Arch. Environ. Contam. Toxicol. 19, 314-319, 1990) and the hypoxia was of stagnant type due to tissue hypoperfusion resulting from hypovolemic hypotension in rabbits administered MIC subcutaneously (Jeevarathinam et al., Toxicology 51, 223-240, 1988). The present study was designed to investigate whether MIC could induce histotoxic hyperoxia through its effects on mitochondrial respiration. Male Wistar rats were used for liver mitochondrial and submitochondrial particle (SMP) preparation. Addition of MIC to tightly coupled mitochondria in vitro resulted in stimulation of state 4 respiration, abolition of respiratory control, decrease in ADP/O ratio, and inhibition of state 3 oxidation. The oxidation of NAD(+)-linked substrates (glutamate + malate) was more sensitive (five- to sixfold) to the inhibitory action of MIC than succinate while cytochrome oxidase remained unaffected. MIC induced twofold delay in the onset of anerobiosis, and cytochrome b reduction in SMP with NADH in vitro confirms inhibition of electron transport at complex I region. MIC also stimulated the ATPase activity in tightly coupled mitochondria while lipid peroxidation remained unaffected. As its hydrolysis products, methylamine and N,N'-dimethylurea failed to elicit any change in vitro; these effects reveal that MIC per se acts as an inhibitor of electron transport and a weak uncoupler. Administration of MIC sc at lethal dose caused a similar change only with NAD(+)-linked substrates, reflecting impairment of mitochondrial respiration at complex I region and thereby induction of histotoxic hypoxia in vivo.
 ...
PMID:In vitro and in vivo effect of methyl isocyanate on rat liver mitochondrial respiration. 147 Nov 48

Evidence suggests a positive correlation between metabolic rate (VO2), or ambient oxygen (O2) tension, and the rate of formation of free radicals from O2. We have previously demonstrated that the rates of growth, VO2, protein and DNA accumulation, and the activity of cytochrome oxidase (a key mitochondrial respiratory enzyme), are increased significantly by exposing the chick embryo to 72 h of hyperoxia (60% O2) late in incubation. To test the hypothesis that the chick embryo responds to a prenatal alteration in O2 availability in such a way as to protect its tissues from oxidative damage, we have used the thiobarbituric acid assay to estimate lipid peroxidation (a major form of free radical damage) in selected organs from chick embryos exposed to altered O2 availability. We found significantly higher concentrations of malondialdehyde (MDA, a secondary product of lipid peroxidation) in liver than in chorioallantoic membrane, brain, or heart. However, embryos exposed to brief (72 h) hypoxia (15% O2) or hyperoxia (60% O2) late in incubation, or 48 h of such exposure followed by 24 h of incubation in pure O2, exhibited no significant difference in MDA levels compared to normoxic (21% O2) controls in any of the tissues examined. We conclude that the increase in aerobic metabolism induced in the chick embryo by 3 days of hyperoxia is not accompanied by an increase in lipid peroxidation. We postulate that the chick embryo adapts to hyperoxia in such a way as to escape additional free radical damage, perhaps by increasing the capacity of its antioxidant defenses to compensate for a potential increase in the rate of free radical generation.
 ...
PMID:Prenatal oxidative stress: I. Malondialdehyde in hypoxic and hyperoxic chick embryos. 237 60

Heart ventricles from chick embryos incubated in 60% O2 (hyperoxia) on the 16th through the 18th days of incubation were 21% heavier than those from control embryos maintained in 21% O2 (normoxia). Heart ventricles from embyros incubated in 15% O2 (hypoxia) were 8% lighter than controls. Changes in ventricular weight were accompanied by proportional changes in protein content (21% more in hyperoxic ventricles; 8% less in hypoxic ventricles). Ventricular tissue DNA content showed a significant increase in hyperoxia. Tissue protein/DNA ratios were significantly higher in hyperoxia and lower in hypoxia. These data suggest that increased O2 availability led to hypertrophy of chick embryo ventricular cells and an increase in the level of DNA synthesis. Cytochrome oxidase activity per mg DNA was 15-25% higher in hyperoxic ventricles than in hypoxic ventricles. This result is consistent with our previous findings that alterations in O2 availability affect the O2 consumption rate of the chick emryo in ovo, and it provides direct evidence that a phenomenon repeatedly observed in vitro is of importance in vivo. In contrast to the heart, O2 availability did not affect the wet weight, protein or DNA contents, or cytochrome oxidase activity of the chick embryo brain.
 ...
PMID:O2 effect on composition of chick embryonic heart and brain. 255 50

The present study was conducted on bone tissue responses to irradiation towards a treatment model of mandibular irradiation injury by comparing the results of experimental observations of irradiation effects on rabbit hind legs and rat mandibular bones (paper I, II and III) with clinical observations of irradiation effects on the human mandible (paper IV, V and VI). The main results of the study were as follows: Bone marrow haemorrhage, eosinophilia and incipient edema were encountered in the rabbit leg one day after a single irradiation dose. Edema and fibrosis were the salient features after five weeks, while both regenerative and fibrotic changes predominated eleven weeks after irradiation. The changes were the more extensive the greater the irradiation dose was. Empty lacunae as a sign of cell damage in cortical bone already appeared on the first day after irradiation; this effect reached its maximum when the dose was 20 Gy or more. Bone marrow and subcutaneous tissue pO2 and pCO2 were measured by means of implanted Silastic tonometers in irradiated and nonirradiated rabbit hind legs. Single dose irradiation was followed by a rapid, dose dependent decrease of marrow pO2. The corresponding effect on pCO2 was weaker and appeared later. The response to hyperoxia in the bone marrow became weaker when the irradiation dose increased. Less significant was the response of CO2 tension to hyperoxia. O2 and CO2 tensions were recovered after single dose irradiation both in subcutaneous tissue and in bone marrow, but the reduction was less in bone marrow. During the twelve weeks observation period clearly better recovery in tissue gas tensions was observed in subcutaneous tissue than in bone marrow. Nonirradiated periosteal grafts on irradiated bone cavities in the rabbit tibia induced more rapid and intense mature bone formation than irradiated periosteal grafts. The irradiated periosteum, even after a single dose of 20 Gy, had some osteogenetic capacity. The alkaline phosphatase content was lowered eight weeks after surgery in irradiated legs but clearly exceeded control values twelve weeks after surgery indicating new bone formation. Lysosomal enzyme DAP II contents were increased in all irradiated specimens as a sign of disturbed bone formation. The tissue concentrations of acid phosphatase, cytochrome oxidase, lactate dehydrogenase, isocitrate dehydrogenase, glucose-6-phosphate dehydrogenase and succinate dehydrogenase in the immediate postirradiation period showed a greater increase in activity in the cut lines of the irradiated rat mandibles than in those of the nonirradiated mandibles.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Bone tissue response to irradiation and treatment model of mandibular irradiation injury. An experimental and clinical study. 309 Aug 54

Rats exposed to 10 to 11 per cent oxygen for 7 days develop tolerance to hyperoxia and can survive for prolonged periods in 100 per cent oxygen. This preexposure to hypoxia is associated with a 180 per cent increase in the activity of the mangani superoxide dismutase but no increase in activity of copper-zinc superoxide dismutase, glucose-6-phosphate dehydrogenase, or the mitochondrial enzymes, cytochrome oxidase and succinate cytochrome c reductase. Cyanide-insensitive oxygen uptake is also increased after this exposure to hypoxia suggesting that an enhanced rate of production of partially reduced species of oxygen may occur. Morphometric and morphologic studies of lung structure demonstrate that no substantial change in cell population characteristics occur in the lungs of animals exposed to hypoxia, but there are ultrastructure changes in the cytoplasm of pulmonary capillary endothelial cells consistent with focal hypertrophy and enhanced metabolic activity of these cells.
 ...
PMID:Structural and biochemical adaptive changes in rat lungs after exposure to hypoxia. 682 93

It is now possible to detect quantitative changes in cytochrome aa3 by means of near-infrared spectrophotometry. This technique is also suitable for determining oxidised hemoglobin (HbO2), reduced hemoglobin (Hb), cerebral blood volume, and the redox state of cytochrome aa3 (cyt aa3) in the tissues. The significance of elevated cyt aa3, measured by near-infrared spectrophotometry, is still unclear, so we investigated this question using both near-infrared spectrophotometry and oxygen saturation meters in endotoxemic dogs. Ten anaesthetised mongrel dogs were injected with endotoxin (E. coli 0111: B4 Difco 2 mg/kg i.v.) and the redox state of Hb and cyt aa3 was determined in real time by near-infrared spectrophotometry. The levels of arterial and cisternal venous oxygen saturation were recorded simultaneously by two Oximetrix 3 saturation meters to calculate the cerebral arterial and venous oxygen saturation difference (Sata-vO2D) in real time. HbO2 decreased along with the fall in mean arterial pressure and remained at a low level, while Hb increased and remained at a high level. The cerebral blood volume decreased in the endotoxic early stage and then returned gradually towards baseline. Cyt aa3 showed an increase following endotoxin injection and maintained an oxidised form. The cerebral Sata-vO2D rose to about three times the control level. From these observations, an increase of oxidised cytochrome aa3 after endotoxin administration seems to be a compensatory protective effect in response to the cerebral oxygen demand rather than over-oxygenation or hyperoxia.
 ...
PMID:Significance of elevated cytochrome aa3 in a state of endotoxemia in dogs. 895 75

The premature primate exposed to hyperoxia provides a useful model of bronchopulmonary dysplasia. A critical target in hyperoxic injury is the mitochondrial matrix enzyme aconitase. We hypothesized that this enzyme's activity would decline in the premature baboon lung during exposure to hyperoxia. Total aconitase activity was significantly decreased in the lungs of premature baboons of 140 days gestation with exposure to 100% oxygen for 6-10 days compared with as needed [pro re nada (PRN)] oxygen exposure and fetal controls (P = 0.0001). In activity gels, lungs from 100% oxygen-exposed animals (6-10 days) showed a nearly complete loss of mitochondrial aconitase activity relative to lungs from animals exposed only to PRN oxygen. Decreased lung aconitase activity was not a nonspecific effect of hyperoxia, causing mitochondrial damage or loss, because the activity of the mitochondrial respiratory enzyme cytochrome oxidase was not different in lungs of 100% oxygen-exposed relative to PRN oxygen-exposed newborns. In 125-day-gestation premature primates (age 6-10 days), lung total aconitase activity was correlated with inspired oxygen tension (r = 0.73 for fraction of inspired oxygen > 0.35), whereas, for animals of 140 days gestation, no such correlation was found. Thus the more premature animal's lung was more susceptible to loss of aconitase.
 ...
PMID:Loss of lung mitochondrial aconitase activity due to hyperoxia in bronchopulmonary dysplasia in primates. 945 10

Cytochrome oxidase activity from the retina can be enhanced or depressed by free radical-mediated reactions both in positive and negative aspect. The greatest effect was exerted by ischemia/reperfusion, which significantly increased the fluorescent products of lipid peroxidation (358 %, P < 0.01) and inhibited the enzyme activity (14%, P < 0.001). After hyperoxia the fluorescent products slightly increased (192%, P < 0.05) as well as the enzyme activity (133 %, P < 0.05). Hypoxia had no effect on any of these parameters. Specific changes in the composition of fluorophores after ischemia/reperfusion were revealed in the fluorescence spectra. The fact that increased lipid peroxidation after hyperoxia and after ischemia/reperfusion does not produce the same effect upon cytochrome oxidase activity might be explained by changes in the kinetic behavior of cytochrome oxidase. In the control enzyme preparation, two binding sites for cytochrome c were observed. One was of the low-affinity (Km = 60 microM) and the other of the high-affinity (Km = 1.12 microM). After in vitro-initiated lipid peroxidation, the low-affinity binding site was lost and the activity measured under "optimum" conditions at a single cytochrome concentration was higher than in the controls. This implies that oxidative damage to cytochrome oxidase in vivo can be site-specific and its extent should be estimated by performing detailed kinetic analysis as otherwise the results might be misleading.
 ...
PMID:The effects of hyperoxia, hypoxia, and ischemia/reperfusion on the activity of cytochrome oxidase from the rat retina. 1152 37


1 2 Next >>