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)

In order to investigate the oxidative component of adriamycin-induced cardiotoxicity in the rat, we used neonatal cardiac myocytes in culture. All incubations, with or without adriamycin (ADM), were performed under normoxic circumstances and additionally under circumstances which make cells more vulnerable towards oxidative challenges: hyperoxia or treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). ADM (100 microM) produced a decrease in the beating rate and enzyme release of the cultures. These effects were potentiated by hyperoxia and by BCNU treatment. Cellular GSH was depleted due to ADM. However, no significant increase in GSSG could be detected, even if the O2-concentration was increased. Lipid peroxidation, measured as thiobarbituric acid reactive material, could be detected only in case ADM plus additional stress were given to the cells. It is concluded that redox-cycling of ADM occurs in rat cardiac myocytes. Formation of ADM-glutathione conjugates or mixed disulfides is strongly indicated. From this it can be inferred that ADM-toxicity in cardiac cells may involve an oxidative mechanism. An important role for the glutathione system is indicated in the detoxification of reactive intermediates. In addition the results implicate that neonatal rat heart cell cultures provide a good screening system for the evaluation of oxidative challenges in the cardiotoxic action of anthracycline analogs.
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PMID:The involvement of an oxidative mechanism in the adriamycin induced toxicity in neonatal rat heart cell cultures. 398 69

Total glutathione levels and the activity of enzymes associated with antioxidant protection in neonatal lung are increased in response to hyperoxia. Glutathione levels in developing rat lung decreased from 24 nmol/mg protein on day 19 of gestation to approximately 12 nmol/mg protein at birth. The initial decrease in glutathione may be due to emergence of other antioxidant systems. Newborn rats placed in 100% oxygen showed a rapid and sustained increase in total glutathione levels which was primarily due to an increase in reduced glutathione. Explants obtained from 16-wk gestation human fetal lung or from 17- to 18-day fetal rat lung also showed increased total and reduced glutathione when cultured in 95% oxygen, 5% CO2 as compared with explants cultured in room air. Type II cells isolated from neonatal rats maintained in oxygen for 6 days also showed glutathione levels twice those found in cells isolated from animals in room air. The activity of antioxidant enzymes (glucose-6-phosphate dehydrogenase, glutathione peroxidase, glutathione reductase) was increased in lungs of newborn rats exposed to 100% oxygen either at birth or 2 days of age. Antioxidant enzyme activity of lung explants cultured in 95% oxygen, 5% CO2 was also higher than in explants maintained in room air. These results suggest that the increases in glutathione and of antioxidant enzymes in vivo and in vitro are a direct effect of oxygen exposure in lung and that the increase of both glutathione and antioxidant enzyme activity is intrinsic to the lung cell itself. It is likely that increases in glutathione in lung represent an important protective mechanism against oxidant injury.
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PMID:The responses of glutathione and antioxidant enzymes to hyperoxia in developing lung. 403 84

Reduced glutathione (GSH) protects alveolar macrophages (AMs) and polymorphonuclear leukocytes (PMNs) against oxidative damage. To obtain further knowledge of the oxygen toxicity we determined GSH in AMs and PMNs of guinea pigs exposed to an oxygen concentration of 85% for up to 90 h. AMs and PMNs from control animals contained 17.93 and 11.67 nmol GSH/mg protein, respectively. During the exposure to a FIO2 of 85% we observed a significant continuous increase of GSH in AMs. By 90 h of oxygen exposure, AMs contained 51.22 nmol GSH/mg protein. In addition, the protein content of AMs decreased during hyperoxia. In contrast, no change of the GSH amount and protein content was detectable in PMNs. The increase of GSH in AMs could serve as an adaptation of the cells to hyperoxia. The lack of the GSH increase in PMNs could be due to the different oxygen concentrations between the lung and the peritoneal cavity. The greater GSH content in AMs may account for the difference between these cells in their susceptibility to oxidant injury.
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PMID:Effect of hyperoxia on reduced glutathione in alveolar macrophages and polymorphonuclear leukocytes. 408 11

The anticancer drug 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) inhibits glutathione reductase, an enzyme involved in oxidant defense systems. The 30-day LD50 for BCNU in male and female BALB/c mice was 52 and 46 mg/kg, respectively. A 35-mg/kg BCNU dose was not lethal to any animal. Glutathione reductase was inhibited in lung tissue by about 50% for 4 days following a single 35 mg/kg dose of BCNU. The prolonged inhibition of glutathione reductase by BCNU suggested this drug might enhance pulmonary oxygen toxicity by diminishing the lung's antioxidant capacity. Exposing mice treated with 35 or 50 mg/kg BCNU to continuous 85% oxygen decreased the LT50 from 13.1 to 6.3 and 5.3 days, respectively, compared to vehicle-treated controls. All mice treated with 35 mg/kg BCNU or vehicle and exposed to 85% oxygen only on Days 0-4 survived to Day 30. Extending the hyperoxic exposure 1 additional day resulted in the death of all BCNU-treated mice, while 70% of the vehicle-treated mice survived to Day 30. Pulmonary glutathione peroxidase, catalase, and superoxide dismutase activities were unaffected up to 6 days following 35 mg/kg BCNU, 85% oxygen, or both. Pulmonary glutathione reductase activity was unaffected by 85% oxygen alone, although hyperoxia extended the BCNU-induced inhibition of this enzyme to Day 6. BCNU, 35 mg/kg, had little effect on lung reduced glutathione (GSH) levels. A significant decrease was only measured on Day 4. Hyperoxia, either alone or with BCNU, had no effect on lung GSH content.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enhanced oxygen toxicity following treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea. 651 Jun 7

Rats treated with low doses of bacterial endotoxin have been shown to be protected from oxygen poisoning under normobaric conditions. Induction of lung activity of the antioxidant enzymes glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) has been reported to occur with endotoxin administration. GSH-Px is a selenoenzyme and selenium-deficient rats have decreased lung GSH-Px activity and enhanced lung toxicity during a hyperoxic exposure. To determine whether bacterial endotoxin administration can provide protection for animals with decreased antioxidant defenses, selenium-deficient and control rats received daily intraperitoneal injections of 250 micrograms/kg bacterial endotoxin or phosphate-buffered saline (PBS) during normobaric exposure to greater than 95% O2. Both groups of animals were protected from hyperoxia by bacterial endotoxin administration despite the extremely low lung GSH-Px activity in the selenium-deficient rats. GSH-Px, SOD, or CAT activities were not induced in the selenium-deficient rats by 48 hr (the time when the selenium-deficient rats treated with PBS began to die). In the selenium-deficient rat, mechanisms other than enzyme induction appear to be providing early protection from hyperoxia.
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PMID:Endotoxin protects selenium-deficient rats from hyperoxia. 669 Jun 38

Thirty-minute perfusion of isolated rabbit lungs with a Krebs-Ringer bicarbonate buffer containing 420 microM paraquat (PQ) or nitrofurantoin (NF) resulted in increases in lung oxidized glutathione (GSSG) content of 589 and 2656%, respectively, over control levels. The degree of glutathione efflux was also increased with both agents, i.e. 77 and 238% above control leakage for PQ and NF respectively. The pulmonary toxicity of both compounds is known to be heightened by conditions of hyperoxia(O2). Ventilation of lungs with 95% O2-5% CO2 did not, in itself, significantly alter glutathione efflux, GSH or GSSG levels. However, ventilation with 95% O2-5% CO2 increased lung GSSG levels in PQ-perfused lungs 225% over PQ-air-perfused lungs, a combined effect not observed with NF-O2, wherein mean GSSG levels were only 72% of that observed with NF-air. Glutathione efflux in PQ-O2-treated lungs declined somewhat (20%) compared to that observed with PQ-air, but a significant increase in the amount of glutathione efflux was seen with NF-O2-treated lungs, i.e. 120 and 310%, respectively, over that attributable to NF or O2 alone. Although the biochemical mechanisms of toxicity of these compounds are thought to be very similar, the disparate degree of GSH oxidation observed with equimolar levels of PQ and NF may indicate differences in reactivity towards glutathione and other lung sulfhydryl pools. The stimulation of the oxidative effects of PQ and NF on lung GSH due to hyperoxic ventilation may be related to the reported O2 enhancement of their toxicity.
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PMID:Glutathione status of isolated rabbit lungs. Effects of nitrofurantoin and paraquat perfusion with normoxic and hyperoxic ventilation. 671 39

Hyperoxic cardiopulmonary resuscitation (CPR) is associated with an increase in neurologic dysfunction upon successful resuscitation with much of the damage attributable to an increase in reperfusion oxidant injury. We hypothesized that by contrast, hypoxic ventilation during resuscitation would improve neurologic outcome by reducing available substrate necessary for oxidant injury. Specifically, this study investigated the effects of 2 levels of hypoxic ventilation during resuscitation: F1O2 = 0.085, PaO2 = 26.6 +/- 3.4 mmHg, (HY8), and F1O2 = 0.12, PaO2 = 33.0 +/- 4.2 mmHg, (HY12), and normoxic resuscitation: F1O2 = 0.21, PaO2 = 60.6 +/- 17.0 mmHg, (N) on survival and neurological outcome following 9 min of normothermic cardiac arrest. Concentrations of malonaldehyde (MDA) and 4-hydroxynonenal (4-OH) in plasma and concentrations of glutathione (GSH) in erythrocyte lysates were measured to quantify possible radical damage. Physiological variables including arterial blood gases were followed for 24 h after resuscitation. Neurologic outcome was assessed using a standardized scoring system. Hypoxically (HY8) resuscitated dogs tended to have a greater neurologic deficit than normoxically resuscitated dogs and had reduced overall survival (16.9 +/- 8.9 h) compared to N dogs (24.0 +/- 0.0 h). Overall survival time correlated negatively (-0.693) and significantly (P = 0.0018) with plasma glucose concentration. Arterial plasma glucose concentrations were higher in the HY8 group compared to the N group immediately (HY8, 312 +/- 86 mg/dL; N, 196 +/- 82 mg/dL; P = 0.17) and 30 min (HY8, 331 +/- 109 mg/dL; N, 187 +/- 74 mg/dL; P = 0.077) following resuscitation. No statistically discernible differences in markers of oxidant injury were apparent among the 3 groups, but pooled data increased significantly with time for MDA and 4-OH. Pooled data for GSH showed a significant drop at 1 h following resuscitation and returned to normal by 6 h. Data from these markers suggested attendant oxidant injury in all groups. Thus, hypoxic ventilation at 2 depths of hypoxia during resuscitation failed to improve neurologic outcome beyond that achieved by ventilation with air, suggesting that normoxia rather than hyperoxia or hypoxia is the ideal target for arterial oxygenation during resuscitation.
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PMID:Hypoxic cardiopulmonary-cerebral resuscitation fails to improve neurological outcome following cardiac arrest in dogs. 1142 82

Exposure to hyperoxia causes alveolar macrophage (AM) injury. The present study investigates the roles of intracellular antioxidant enzymes and of glutathione in the protection of AMs against hyperoxia in a biphasic cell culture system in aerobiosis. The effect of normoxia or hyperoxia on the integrity of AMs was related to indices of cell injury (ATP cell content and lactate dehydrogenase release into culture medium) and cell mass (protein content of AMs). Antioxidant activities were measured in guinea-pig AMs exposed to 95% O2 or to normoxia (control cells) for 3 days. A 3-day AM culture in normoxia showed a significant decrease in protein and catalase, whereas ATP cell content, superoxide dismutase (SOD) (both Cu,Zn-SOD and Mn-SOD) and glutathione peroxidase (GPx) activities significantly increased. The content of reduced glutathione (GSH) did not change. Using the ATP content in AMs expressed as a cell injury index (CII), AM injury increased with increasing O2 exposure time (1 day: 13 +/- 4.4%; 2 days: 34 +/- 3.8%; 3 days: 40 +/- 4.1%; 4 days: 55 +/- 7.3%; 6 days: 87.5 +/- 5.4%). Exposure to 95% O2 for 3 days was associated with a significant decrease in ATP cell content, protein, catalase and GSH to the total glutathione ratio, whereas SOD, GSH and total glutathione did not change significantly. The GPx activities increased significantly. There was no significant correlation between the AM CII and SOD or GPx content. In contrast, a significant correlation was observed between hyperoxia-induced AM CII and catalase content (r = 0.71) and glutathione content (r = 0.71).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationship between oxygen-induced alveolar macrophage injury and cell antioxidant defence. 774 27

Glutathione reductase (GR) protects tissues from oxidant injury by catalysing the reduction of glutathione disulfide (GSSG) to glutathione (GSH). In order to study the effect of GR in protecting cells from oxidant injury, we generated Chinese hamster ovary (CHO) cell lines stably transformed after antisense-oriented gene transfection. The coding region of the human GR was cloned using revere transcription PCR method and selected by transient expression study in mammalian cells. A clone HGR135 showed overexpression of GR in CHO cells and was proved to have no base substitution. This clone, then, was ligated into MEP4 expression vector in an antisense orientation to the human metallothionein promoter and transfected to CHO cells with polybrene. Among 12 cell lines isolated, G17 showed to have the least GR activity (48% of the control), while another four were mildly GR deficient. Southern hybridization of genomic DNA digests and transformation experiment on E. coli revealed that the promoter-antisense coding region component was integrated. Northern hybridization detected reduced amount of GR transcript but no antisense message. Baseline cellular GSH concentrations were lower in G17 than in control (25.7 +/- 2.5 vs. 36.1 +/- 1.9 nmole/mg protein, P < 0.05), while cellular GSSG concentrations were higher (0.61 +/- 0.19 vs. 0.39 +/- 0.09 nmole/mg protein, P < 0.05). After four hours of treatment of G17 and control cells with increasing doses (1 to 10 mM) of t-butylhydroperoxide (t-BuOOH), cellular GSH concentrations in G17 decreased with an elevation of GSSG concentration at 1 mM followed by no further increase at higher t-BuOOH concentration, while GSSG concentrations increased in the control cells without reduction of GSH concentrations at 1-5 mM t-BuOOH treatment. The concentrations of GSH were lower in G17 than in controls at all doses of t-BuOOH. Four hours of exposure to 10 mM t-BuOOH resulted in greater LDH release in G17 than in control (57.3 +/- 4.7 vs. 32.1 +/- 6.5%, P < 0.05). Similarly, G17 cells released more of their LDH to the media than did CHO cells in response to exposure to 95% O2 for 72 hours (19.3 +/- 5.9 vs. 11.9 +/- 5.4%, P < 0.05). The partial GR deficiency in G17 cells impairs their ability to recycle GSSG and this deficiency offers the best explanation for the increased sensitivity of these cells to injury by t-BuOOH or hyperoxia.
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PMID:[Establishment of Chinese hamster ovary cell lines with reduced expression of glutathione reductase after antisense-oriented gene transfection and assessment of the sensitivity to oxidant injury]. 786 64

Glutathione (GSH) administered intraperitoneally significantly prolongs the time to initial seizure and survival time of rats exposed to hyperbaric hyperoxia (HBO). Acivicin is an antitumor antibiotic that is an inhibitor of gamma-glutamyl transpeptidase (GGT), an enzyme necessary for the breakdown and transport across cell membranes of GSH. To determine whether acivicin treatment alters GSH-induced protection from HBO, rats were dosed with 25 mg/kg of acivicin or vehicle 1 h before O2 exposure at an inspired O2 fraction of 1.0 at 4 ATA. Immediately before exposure, rats received GSH (1 mmol/kg) or vehicle. Time to seizure and time to death were recorded during exposure by direct observation. In separate groups of rats on the same dosing schedule, plasma GSH, renal GGT, and brain GGT were measured 15 min after the GSH injection without HBO exposure and 100 min after the beginning of HBO exposure. Renal GGT was decreased to 2.5% of control and brain GGT to 37% of control in the acivicin-dosed rats. Plasma GSH increased 3-fold in rats given acivicin alone, 52-fold in rats given GSH alone, and 84-fold in rats receiving both acivicin and GSH. Rats dosed with GSH alone had significantly prolonged times to seizure and death compared with all other groups. Rats dosed with GSH after receiving acivicin were not protected from HBO despite the large increase in plasma GSH that occurred in these animals. GSH treatment did not increase tissue GSH in lung, liver, or brain at 160 or 200 min of exposure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Elimination of glutathione-induced protection from hyperbaric hyperoxia by acivicin. 791 99

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