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

Among vertebrates, adult amphibians are known to be especially tolerant to exposure to high environmental oxygen tensions. To clarify the basis for this high O2 tolerance, adult Rana ridibunda perezi frogs were acclimated for 15 days to water-air phases with either 149 mm Hg O2 (normoxia) or 710 mm Hg O2 (hyperoxia). At the end of the acclimation, various morphometric and biochemical parameters related to oxidative stress were measured in seven organs and tissues. Hyperoxia acclimation did not change either the total weight of the animals or the total and relative wet weights of the organs studied, except for the brain, which showed weight increases in the hyperoxic group. In vivo tissue peroxidation increased in the kidney; decreased in the skeletal muscle and skin; and did not change in the liver, lung, brain, and heart after hyperoxic exposures. Whereas liver, lung, and skin showed glutathione peroxidase (GSH-Px) activities with both cumene hydroperoxide (cumene-OOH) and H2O2 as substrates, skeletal muscle only showed H2O2 GSH-Px activity. Hyperoxia acclimation did not change either catalase (CAT) or GSH-Px activities in any organ, except for the liver in which CAT activity was induced by hyperoxia. Thus hyperoxia tolerance in this species does not need the induction of H2O2-detoxifying enzymes in the majority of the organs. It is suggested that the high O2 tolerance of this amphibian species is related to its comparatively high constitutive GSH-Px activities.
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PMID:Effect of hyperoxia acclimation on catalase and glutathione peroxidase activities and in vivo peroxidation products in various tissues of the frog Rana ridibunda perezi. 318 4

Buthionine sulfoximine (BSO), an inhibitor of de novo synthesis of glutathione (GSH), was used to deplete rats of GSH and determine the effect of treatment on antioxidant enzyme responses, lung injury, and the susceptibility to concurrent sublethal or lethal hyperoxia. In a preliminary experiment, total lung nonprotein sulfhydryl (NPSH) and GSH levels were measured at various times after single doses of BSO. The lowest concentrations were observed at 12 to 18 h. These experiments were used to establish a repeated dosing protocol for more prolonged GSH depletion. The lungs of rats treated with BSO for 4 days demonstrated markedly decreased GSH and NPSH levels (10 to 40% of control values) and glutathione peroxidase activity (45 to 60% of control values). Superoxide dismutase activities were elevated, glutathione reductase activity was slightly elevated, and catalase activity was unchanged. These changes were dose-responsive. The lungs of treated rats were grossly and microscopically normal. BSO treatment of additional rats did not increase susceptibility to lethal hyperoxia (greater than 98% oxygen). Combined treatment of rats with both BSO and sublethal hyperoxia (80% oxygen) for 4 days did not alter the biochemical responses demonstrated by rats treated solely with BSO. The marked increase in catalase activity obtained after hyperoxia alone was not observed in rats treated with both hyperoxia and BSO. The lungs of saline- and BSO-treated rats exposed to sublethal hyperoxia demonstrated a patchy distribution of slight perivascular and peribronchiolar edema.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The pulmonary effects of buthionine sulfoximine treatment and glutathione depletion in rats. 320 1

Preexposure to hypoxia increased survival and lung reduced glutathione-to-oxidized glutathione ratios (GSH/GSSG) and decreased pleural effusions in rats subsequently exposed to continuous hyperoxia. In addition, lungs from hypoxia-preexposed rats developed less acute edematous injury (decreased lung weight gains and lung lavage albumin concentrations) than lungs from normoxia-preexposed rats when isolated and perfused with hydrogen peroxide (H2O2) generated by xanthine oxidase (XO) or glucose oxidase (GO). In contrast, when perfused with elastase or exposed to a hydrostatic left atrial pressure challenge, lungs isolated from hypoxia-preexposed rats developed the same acute edematous injury as lungs from normoxia-preexposed rats. The mechanism by which hypoxia preexposure conferred protection against H2O2 appeared to depend on hexose monophosphate shunt (HMPS)-dependent increases in lung glutathione redox cycle activity. First, before perfusion with GO, lungs from hypoxia-preexposed rats had increased glutathione peroxidase and glucose 6-phosphate dehydrogenase (but not catalase or glutathione reductase) activities compared with lungs from normoxia-preexposed rats. Second, after perfusion with GO, lungs from hypoxia-preexposed rats had increased H2O2 reducing equivalents, as reflected by increased GSH/GSSG and NADPH/NADPH+, compared with lungs from normoxia-preexposed rats. Third, pretreatment of rats with an HMPS inhibitor, (6-aminonicotinamide) or a glutathione reductase inhibitor, [1,3-bis(2-chloroethyl)-1-nitrosourea] prevented hypoxia-conferred protection against H2O2-mediated acute edematous injury in isolated lungs. These findings suggest that increased detoxification of H2O2 by glutathione redox cycle and HMPS-dependent mechanisms contributes to tolerance to hyperoxia and resistance to H2O2 of lungs from hypoxia-preexposed rats.
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PMID:Hypoxia increases glutathione redox cycle and protects rat lungs against oxidants. 321 62

1. Various parameters related to oxidative stress were measured in adult Discoglossus pictus acclimated for 15 days to either normoxia or hyperoxia (PO2 = 710 mmHg). 2. Total weight of the toads and total and relative wet weight of liver, kidneys, lungs and heart were not changed by hyperoxic acclimation. 3. In vivo tissue peroxidation increased in lung, decreased in skeletal muscle, and was not changed in liver, kidney, heart and skin after hyperoxic exposure. 4. Hyperoxic acclimation increased catalase activities in the lung, liver, kidney and heart but not in skeletal muscle and skin. 5. Liver showed higher GSH-peroxidase activity with cumene-OOH than with H2O2 as substrate, whereas lung, skeletal muscle and skin presented similar GSH-peroxidase activities with both substrates. 6. GSH-peroxidase activities did not change between hyperoxic and normoxic animals in liver, lung, skeletal muscle and skin. 7. These results show that catalase, not GSH-peroxidase, is the principal H2O2 detoxifying enzyme involved in the adaptation of D. pictus to hyperoxia.
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PMID:Physiological significance of catalase and glutathione peroxidases, and in vivo peroxidation, in selected tissues of the toad Discoglossus pictus (Amphibia) during acclimation to normobaric hyperoxia. 324 21

Single, preexposure, parenteral injection with both recombinant tumor necrosis factor/cachectin (TNF/C) and interleukin-1 (IL-1) prolonged the survival of rats (144 +/- 9 h) in continuous hyperoxia (greater than 99% O2 at 1 atm) when compared with rats injected with boiled TNF/C and boiled IL-1 (61 +/- 2 h), TNF/C alone (61 +/- 2 h), IL-1 alone (62 +/- 2 h), or saline (64 +/- 3 h). After exposure to hyperoxia for 52 h, pleural effusion volume, pulmonary artery pressure, total pulmonary resistance, and lung morphologic damage were decreased in those rats given TNF/C and IL-1 as compared with saline-injected rats. In parallel, ratios of reduced (GSH) to oxidized (GSSG) glutathione were greater (P less than 0.05) in lungs of TNF/C + IL-1-injected rats (91 +/- 20) than of saline-injected rats (30 +/- 4) that had been exposed to hyperoxia for 52 h. No differences were found in superoxide dismutase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase, or catalase activities in lungs of TNF/C + IL-1- or saline-treated, hyperoxia-exposed rats. Our results indicate that pretreatment with TNF/C and IL-1 favorably altered lung glutathione redox status, decreased lung injury, and enhanced survival of rats exposed to hyperoxia.
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PMID:Recombinant tumor necrosis factor/cachectin and interleukin 1 pretreatment decreases lung oxidized glutathione accumulation, lung injury, and mortality in rats exposed to hyperoxia. 349 53

The effects of oxidative stress caused by hyperoxia or administration of the redox active compound diquat were studied in isolated hepatocytes, and the relative contribution of lipid peroxidation, glutathione (GSH) depletion, and NADPH oxidation to the cytotoxicity of active oxygen species was investigated. The redox cycling of diquat occurred primarily in the microsomal fraction since diquat was found not to penetrate into the mitochondria. Depletion of intracellular GSH by pretreatment of the animals with diethyl maleate promoted lipid peroxidation and sensitized the cells to oxidative stress. Diquat toxicity was also greatly enhanced when glutathione reductase was inhibited by pretreatment of the cells with 1,3-bis(2-chloroethyl)-1-nitrosourea. Despite extensive lipid peroxidation, loss of cell viability was not observed, with either hyperoxia or diquat, until the GSH level had fallen below approximately 6 nmol/10(6) cells. The iron chelator desferrioxamine provided complete protection against both diquat-induced lipid peroxidation and loss of cell viability. In contrast, the antioxidant alpha-tocopherol inhibited lipid peroxidation but provided only partial protection from toxicity. The hydroxyl radical scavenger alpha-keto-gamma-methiol butyric acid, finally, also provided partial protection against diquat toxicity but had no effect on lipid peroxidation. The results indicate that there is a critical GSH level above which cell death due to oxidative stress is not observed. As long as the glutathione peroxidase - glutathione reductase system is unaffected, even relatively low amounts of GSH can protect the cells by supporting glutathione peroxidase-mediated metabolism of H2O2 and lipid hydroperoxides.
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PMID:Effects of oxidative stress caused by hyperoxia and diquat. A study in isolated hepatocytes. 350 39

We compared the effects of 95% O2 (hyperoxia) alone, endotoxin (20 ng/ml) alone, and 95% O2 plus endotoxin on the release of lactate dehydrogenase (LDH), uptake of 5-hydroxytryptamine (5-HT), and antioxidant enzyme activities in porcine pulmonary arterial and aortic endothelial cells in monolayer culture. Hyperoxia increased LDH release and decreased 5-HT in both endothelial cell types. Hyperoxia also caused a decrease in catalase (CAT) activity and an increase in total superoxide dismutase (SOD) and glutathione reductase (GSH-Red) activities in both cell types. Endotoxin alone had no effect on LDH release, 5-HT uptake, or antioxidant enzyme activities. However, endotoxin prevented the hyperoxic increase in LDH release and the hyperoxic decrease in 5-HT uptake. Endotoxin plus 95% O2 had no consistent effect on the antioxidant enzyme profile in pulmonary artery or aortic endothelial cells. These results indicate that (1) hyperoxia injures both pulmonary artery and aortic endothelial cells in culture and causes changes in the antioxidant enzyme profile that are similar in the two cell types; (2) hyperoxia-induced decreases in CAT activity and increases in SOD activity may be responsible for increased sensitivity of endothelial cells to O2 toxicity; and (3) endotoxin protects against hyperoxic injury to endothelial cells in vitro, but increases in antioxidant enzyme activities are not the mechanism for this protection.
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PMID:Effect of oxygen and endotoxin on lactate dehydrogenase release, 5-hydroxytryptamine uptake, and antioxidant enzyme activities in endothelial cells. 388 60

Diethylmaleate (DEM) decreases glutathione (GSH) levels in various organs by enzymatic conjugation with reduced GSH catalyzed by GSH transferase. We have examined levels of GSH, glutathione reductase (GR), and glucose-6-phosphate dehydrogenase (G6PD) in lungs of 200-250-g rats after intraperitoneal injection of 0.5 or 1 g DEM/kg body wt. The GSH levels are severely depressed at 2 and 4 h but have essentially recovered by 12 and 24 h after either dose of DEM. The GR and G6PD activities in the 1 g/kg group are depressed at 4 h to a lesser extent than the GSH levels and also return to normal by 12 and 24 h. These enzymes are not affected in the 0.5 g/kg group. To determine whether these transient decreases in GSH and related enzymes affected O2 tolerance, we exposed rats injected with DEM to greater than 98% O2 and found that halftime (t1/2) for survival was decreased in rats receiving both 0.5 and 1 g DEM/kg body wt when compared with untreated or saline-injected controls (t1/2 control, 74 h; 0.5 g DEM, 59 h; 1 g DEM, 53 h). No deaths occurred in air controls at 1 mg/kg DEM for up to 5 days. DEM, in itself, caused no morphological alteration of the lung. Thus a decrease in lung GSH and related enzymes, occurring by 4 h and reversed by 12 h, has a significant effect on the subsequent progression of lung pathology and indicates that early biochemical events occurring in lungs exposed to hyperoxia may be very important in determining the degree of longer-term damage to rat lungs.
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PMID:Transient depletion of lung glutathione by diethylmaleate enhances oxygen toxicity. 398 Mar 59

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

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


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