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)

Exposure of cultured pulmonary artery endothelial cells to 95% O2 resulted in the following sequence of events: decrease in [3H]thymidine incorporation after 24 h; increase of intracellular glutathione (GSH) and loss of cellular protein after 48 h; increase of spontaneous and decrease of provoked prostacyclin formation as well as increased release of cellular LDH after 72 h. This oxygen toxicity model was used to study the following 2 questions. (1) What is the relative importance of the GSH redox cycle compared to catalase as antioxidative defense against hyperoxia? Endothelial cells were grown in selenium-depleted medium to inhibit glutathione peroxidase activity. Endothelial GSH biosynthesis was inhibited by buthionine sulfoximine. Catalase activity was reduced by aminotriazole. Endothelial cells with an impaired GSH redox cycle were easily killed by hyperoxia within 24 h, while inhibition of catalase did not enhance the susceptibility of endothelial cells to hyperoxia. (2) Can endothelial GSH content be increased by exogenous sulfhydryl reagents and does this result in an increase of endothelial cells' resistance to hyperoxia? Exogenous GSH, N-acetylcysteine, cysteine, and L-2-oxothiazolidine-4-carboxylate (L-2-oxo) increased intracellular GSH. All sulfhydryl reagents (with the exception of L-2-oxo) protected endothelial cells from hyperoxia. Concentrations of exogenous GSH and N-acetylcysteine that did not increase intracellular GSH reduced hyperoxia-induced endothelial cell injury. Thus the capacity of the GSH redox cycle rather than intracellular GSH levels or catalase determines endothelial cells' resistance to hyperoxia.
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PMID:Glutathione redox cycle is an important defense system of endothelial cells against chronic hyperoxia. 192 73

We have studied the effect of various compounds, known as antioxidants, on the level of hyperoxia (80-90% O2)-induced chromosomal aberrations in Chinese hamster ovary cells: ascorbic acid, alpha-tocopherol, carnosine, imidazole-4-acetic acid, glutathione monoethylester, N-acetylcysteine and ethoxyquin. Carnosine (beta-alanyl-histidine) appeared to be the only compound that reduced chromosomal breakage. The effect was also present in cultures post-treated with caffeine (at 2.5 mM, 3 h before harvest), indicating that the apparent protection was not due to selective arrest of chromosomally damaged cells in the G2 phase of the cell cycle. Imidazole-4-acetic acid, a compound structurally very similar to carnosine, had no detectable effect. Ascorbic acid, N-acetylcysteine, glutathione monoethylester and ethoxyquin were found to have a pro-oxidant effect, i.e. they apparently potentiated the clastogenic effect of hyperoxia. Carnosine is the first compound shown to protect against the clastogenicity of normobaric hyperoxia and may thus be a useful tool in elucidating the underlying mechanism.
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PMID:Effect of antioxidants on hyperoxia-induced chromosomal breakage in Chinese hamster ovary cells: protection by carnosine. 194 22

The potential protective effect of N-acetylcysteine against various types of oxidative stress (exposure to hyperoxia, treatment with paraquat, incubation in the presence of the hypoxanthine-xanthine oxidase system) was tested in primary cultures of porcine aortic endothelial cells. It was compared to that of selenomethionine (Se-Met), known to increase glutathione peroxidase activity, when given either alone or in combination with N-acetylcysteine. LDH release, 3H-thymidine (TdR) incorporation into DNA and DNA content were measured to assess the cytotoxic effect of the conditions tested. Total and oxidized glutathione content was also determined. Whereas Se-Met had a partial protective effect on all the conditions but paraquat treatment, N-acetylcysteine administration had no effect on the hyperoxia induced changes and significantly worsened the cytotoxic action of paraquat. On the other hand, LDH release following an incubation in the presence of the hypoxanthine-xanthine oxidase was significantly reduced after N-acetylcysteine treatment. No major change in total nor in oxidized glutathione followed N-acetylcysteine treatment in control and experimental conditions. A dose-dependent protective effect of N-acetylcysteine was obtained when this agent was given concomitantly with the xanthine oxidase system. These data suggest that in cultured endothelial cells a N-acetylcysteine-related protective effect, if present, is most likely to result from the direct scavenging action of N-acetylcysteine.
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PMID:Comparative study on the selenium- and N-acetylcysteine-related effects on the toxic action of hyperoxia, paraquat and the enzyme reaction hypoxanthine-xanthine oxidase in cultured endothelial cells. 368 96

Hyperoxic ventilation, used to prevent hypoxemia during potential periods of hypoventilation, has been reported to paradoxically decrease whole body oxygen consumption (VO2). Reduction in nutritive blood flow due to oxygen radical production is one possible mechanism. We investigated whether pretreatment with the sulfhydryl group donor and O2 radical scavenger N-acetylcysteine (NAC) would preserve whole body VO2 and prevent deterioration of oxygenation in gastric mucosal tissue during hyperoxia. Thirty-eight patients, requiring hemodynamic monitoring (radial and pulmonary artery catheters) due to sepsis syndrome, were included in this randomized experiment. All patients exhibited stable clinical conditions (hemodynamics, body temperature, hemoglobin, FIO2 < 0.5). A gastric tonometer was placed to measure the gastric intramucosal pH (pHi), which indirectly assesses nutritive blood flow to the mucosa. Cardiac output was determined by thermodilution and VO2 by cardiovascular Fick. After baseline measurements, patients randomly received either 150 mg.kg-1 NAC (n = 19) or placebo (n = 19) in 250 ml 5% dextrose intravenously over a period of 15 min. Measurements were repeated 30 min after starting NAC or placebo infusion, 30 min after starting hyperoxia (FIO2 = 1.0), and 60 min after resetting the original FIO2. There were no significant differences between groups in any of the measurements before treatment and after the return to baseline FIO2 at the end of the study. NAC, but not placebo infusion, caused a slight but significant increase in cardiac output and decrease in systemic vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:N-acetylcysteine preserves oxygen consumption and gastric mucosal pH during hyperoxic ventilation. 788 69

The therapeutic efficacy of N-acetylcysteine (NAC) in the management of hyperoxia-induced lung injury was assessed using the preterm guinea pig model of prematurity. Preterm guinea pig pups were delivered by Caesarean section 3 days preterm, and exposed to either 21 or 95% oxygen for 72 hr. NAC (200 mg/kg body weight) or saline was injected twice daily. Bronchoalveolar lavage fluid (BALF) from hyperoxia-exposed pups contained significantly higher protein concentrations and an increased number of neutrophils. NAC partly ameliorated lung injury, preventing the increase in BALF protein concentration, which is generally associated with oedema. There was no effect on the movement of neutrophils into the lung airspaces in response to oxygen. Treatment with NAC had no effect on lung or liver glutathione (reduced) (GSH) concentrations either after 2 hr post-administration, or over the full 72 hr experimental period. An apparent resistance of the lung to increased synthesis or uptake of GSH was demonstrated by the lack of effect of direct administration of GSH, its isopropyl ester or 2-oxo-4-thiazolidine carboxylic acid. Oxygen exposure alone (95%) increased lung concentrations by 60-70%. It would, therefore, appear from this data that NAC may have potential as a future component of antioxidant therapy, although its effects are not mediated through increased GSH levels.
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PMID:N-acetylcysteine ameliorates hyperoxic lung injury in the preterm guinea pig. 845 59

To investigate the mechanisms regulating hyperoxia-induced intercellular adhesion molecule-1 (ICAM-1) expression, we studied the effects of antioxidants on ICAM-1 expression, and the relationship between ICAM-1 expression and extracellular glutathione levels in human pulmonary artery endothelial cells (HPAEC) and human umbilical vein endothelial cells (HUVEC). Cells were cultured to confluence and exposed to hyperoxia (90% O2) for 48 h with or without various antioxidants, including superoxide dismutase (SOD), catalase, N-acetylcysteine (NAC), and glutathione. The levels of ICAM-1 expression in the endothelial cells and the concentrations of reduced (GSH) and oxidized glutathione (GSSG) in the media were examined by flow cytometry and spectrophotometry, respectively. After exposure to hyperoxia, ICAM-1 expression was increased, and the supernatant total glutathione was decreased as compared with those at normoxia. SOD did not change ICAM-1 expression. The hyperoxia-induced increase in ICAM-1 expression was even greater with the addition of catalase. The ICAM-1 expression was decreased and the GSH concentration was increased with the addition of NAC. There were negative relationships between the level of ICAM-1 expression and the supernatant total glutathione concentration in catalase-treated HPAEC (R = 0.822, P < 0.0005) and HUVEC (R = 0.567, P < 0.01). Negative relationships were also demonstrated between the level of ICAM-1 expression and the total extracellular glutathione concentrations in NAC-treated HPAEC (R = 0.877, P < 0.0005) and HUVEC (R = 0.727, P < 0.0005). Exogenous GSH decreased ICAM-1 expression in both hyperoxia-exposed HPAEC and HUVEC, while exogenous GSSG did not. These results suggest that extracellular GSH plays a role in regulating hyperoxia-induced ICAM-1 expression in HPAEC and HUVEC.
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PMID:Modulation of ICAM-1 expression by extracellular glutathione in hyperoxia-exposed human pulmonary artery endothelial cells. 881 Jun 35

Since the description of bronchopulmonary dysplasia (BPD) in premature infants, the supplemental oxygen administered has been suspect in the etiology of BPD. This has prompted studies on the effect of hyperoxia on lung growth in neonatal animals. So far, these have not led to a treatment which either prevents or mitigates BPD. Another approach to investigate the effect of hyperoxia on the immature lung is to use lung explants from 12-d gestation mouse fetuses. Exposing explants to different concentrations of oxygen for 48 h, we found that exposures to oxygen both below (10%) and above (35% or greater) normoxia adversely affected branching morphogenesis and growth. The effect was irreversible at exposures of 50% oxygen and greater. To determine the role of reactive oxygen species (ROS) in the effect of hyperoxia, antioxidants and inhibitors of ROS formation were added to the incubating explants, and their influence on reducing the adverse effect of 50% oxygen was assessed. The combination of CuZn superoxide dismutase (SOD) and catalase, manganese SOD, manganese-3-tetrakis(1-methyl-4-pyridyl)porphorin, a low molecular weight SOD mimetic, and to a lesser extent, deferoximine, an antioxidant and inhibitor of hydroxyl radical formation, were successful in reducing the effect of 50% oxygen on morphogenesis. Not successful were N-nitro-L-arginine methyl ester (an inhibitor of nitric oxide synthase); allopurinol (an inhibitor of xanthine oxidase); N-acetylcysteine and ebselen (a glutathione peroxidase mimetic); Trolox (a synthetic tocopherol); catalase, and CuZnSOD used alone. These results provide evidence that superoxide anion and possibly hydroxyl radical are the ROS most likely responsible for the growth effects of hyperoxia on mouse fetal lung morphogenesis.
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PMID:Oxygen toxicity to the developing lung of the mouse: role of reactive oxygen species. 882 70

Although the effect of hyperoxia on antioxidant enzymes is well known, the effect of subtoxic levels of hyperoxia on gamma-glutamyltransferase (gamma-GT), involved in the degradation and uptake of extracellular GSH for intracellular GSH synthesis, is unknown. The aim of the study was to investigate (1) the effects of in vitro hyperoxia on gamma-GT activity of type II cells and (2) the effects of the lazaroid U-74389G and N-acetylcysteine (NAC) on the hyperoxia-induced changes in gamma-GT and antioxidant enzyme activities. At 48 h after isolation, rat type II cells were exposed for 2 days to air, 60% O2 or 85% O2 with or without 30 microM U-74389G or 100 microM NAC. After the exposure, the cells were harvested and assayed for superoxide dismutase (SOD), glutathione peroxidase (GPx), gamma-GT activity, and GSH levels. In another series of experiments 85% O2-exposed cells, with or without U-74389G, were used for Northern blotting of gamma-GT mRNA. Exposure to 60% O2 decreased gamma-GT and GSH by -47 and -34%, respectively, while SOD and GPx activities remained unchanged. After 85% O2-exposure gamma-GT decreased by -55%, SOD and GPx increased by +55 and +87%, respectively, while GSH decreased by -35%. NAC treatment decreased gamma-GT activity by -42% in the air-exposed cells. After 60% O2, U-74389G led to significantly higher gamma-GT (+117%) and GSH (+26%) while NAC only led to higher GSH (+28%) compared to the oxygen-exposed cells not treated with NAC or U-74389G. After 85% O2 U-74389G increased gamma-GT, SOD, and GSH by +72, +58, and +68%, respectively, while NAC only increased SOD (+49%) and GSH (+26%) compared to the oxygen-exposed cells not treated with NAC or U-74389G. The 85% O2 exposure, with or without U-74389G, had no effect on gamma-GT mRNA levels. The results show that hyperoxia decreases rat type II cell gamma-GT activity in vitro. This effect was not related to an altered regulation at mRNA level and it was not associated with the hyperoxia-induced decrease in intracellular GSH, since restoration of the GSH levels by NAC did not restore gamma-GT activity. The lazaroid U-74389G with vitamin E-like properties effectively prevented the decrease in gamma-GT and GSH, so that direct inactivation of the membrane-bound gamma-GT by hyperoxia is the most likely mechanism.
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PMID:Decrease in gamma-glutamyltransferase activity in rat type II cells exposed in vitro to hyperoxia: effects of the 21-aminosteroid U-74389G. 920 59

The regulating mechanism of hyperoxia-induced ICAM-1 expression has not been elucidated. We studied the effect of antioxidants, including superoxide dismutase (SOD), catalase and N-acetylcysteine (NAC), on hyperoxia-induced ICAM-1 expression in human pulmonary artery endothelial cells (HPAEC) and human umbilical vein endothelial cells (HUVEC). Cells were cultured to confluence and exposed to either hyperoxic or normoxic gas with or without various kinds of antioxidants. The levels of ICAM-1 expression in the endothelial cells and the concentrations of reduced (GSH) and oxidized glutathione (GSSG) in the media were examined by flow cytometry and by spectrophotometry, respectively. After 48-hour exposure to hyperoxia, ICAM-1 expression was increased (HPAEC; 161 +/- 21% and HUVEC; 163 +/- 16%) and total glutathione concentration in the media was decreased as compared with normoxia. SOD did not change the GSH and GSSG concentrations in the media. Catalase dose-dependently decreased the supernatant GSSG concentration in both HPAEC and HUVEC, while the GSH concentration was nearly constant. NAC dose-dependently increased the supernatant GSH concentrations in both HPAEC and HUVEC. There was no difference in the supernatant GSSG concentrations between the NAC-treated HPAEC and HUVEC. There was no difference in ICAM-1 expression in either HPAEC or HUVEC with SOD treatment. ICAM-1 expressions in 100 U/ml (236 +/- 20%) and 1,000 U/ml (315 +/- 36%) of catalase were increased in HPAEC, and that in 1,000 U/ml (440 +/- 209%) of catalase was increased in HUVEC. Five and 10 U/ml of NAC decreased ICAM-1 expression in HPAEC (141 +/- 26% and 113 +/- 11%) and HUVEC (119 +/- 23% and 106 +/- 7%), respectively. These results suggest that extracellular glutathione may play a role in regulating hyperoxia-induced ICAM-1 expression in HPAEC and HUVEC.
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PMID:Effect of antioxidants on hyperoxia-induced ICAM-1 expression in human endothelial cells. 926 67

Although the antioxidant properties of N-acetylcysteine (NAC) in vitro are widely accepted, the efficacy of NAC in the prevention of O2 toxicity in vivo is poorly documented. The aim of our study was to investigate the presumed protective effect of NAC on hyperoxic lung injury, focusing on gamma-glutamyltransferase (gamma-GT) activity and glutathione (GSH) levels in lung tissue, epithelial lining fluid (ELF), and isolated rat type II cells immediately after their isolation and 48 h later when kept in culture in normoxia. Thirty-four male Wistar rats were divided in three groups (n = 10-14) and were exposed to air or to 60 or 85% O2 for 7 days. One-half of the rats in each group received 200 mg/kg NAC intraperitoneally one time per day from 3 days before exposure until the end of the experiment, and the other one-half received the vehicle. In the 85% O2-exposed animals, NAC led to more respiratory distress and weight loss. NAC did not prevent the rise in bronchoalveolar lavage lactate dehydrogenase and alkaline phosphatase, but it did prevent the rise in calculated ELF volume. NAC decreased GSH levels (1.4-fold) and gamma-GT activity (1.8-fold) in the air-exposed type II cells. In the 60% O2-exposed group, no effects of NAC were seen (except for a decrease in gamma-GT mRNA expression), but, in the 85% O2-exposed group, NAC gave rise to higher GSH (2.6-fold) and higher gamma-GT activity (2.9-fold) in the ELF and lower GSH (6.9-fold) and higher gamma-GT activity (3.6-fold) in the type II cells. Even in culture, GSH levels remained 1.5-fold lower than in the cells from the air-exposed animals and 2-fold lower than in the cells from the 85% O2-exposed animals. There was increased DNA damage (as assessed by thymidine incorporation) and apoptosis after hyperoxia, especially after 60% O2, and this effect was amplified after NAC treatment. Although protective at the endothelial side, NAC treatment led to adverse effects at the epithelial side, despite, or probably because of, restoration of the ELF GSH levels in the presence of high O2 levels. Because NAC is rapidly metabolized to cysteine, it is plausible that the effects of NAC are manifested through the toxic effects of cysteine.
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PMID:N-acetylcysteine does not protect against type II cell injury after prolonged exposure to hyperoxia in rats. 931 88

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