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

Cultured type II pneumocyte responses to in vitro normoxia (95% air:5% CO2) or hyperoxia (95% O2:5% CO2) were quantified. Normoxic culture (0 to 96 h) of rabbit type II cells resulted in enhanced cell-monolayer protein and DNA content. During this same time, cellular activities of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH Px) decreased. Compared to cultures maintained in normoxia, hyperoxic exposure of cultures resulted in decreased cell-associated protein and DNA content. Exposure to hyperoxia also resulted in cytotoxicity as demonstrated by elevated cellular release of DNA, lactate dehydrogenase (LDH), and preincorporated 8-[14 C]adenine. Cellular catalase and GSH Px activities in hyperoxic cells decreased similarly to normoxic controls. In contrast, cellular SOD activity in hyperoxic cells decreased less than in normoxic cultures. Cellular SOD activity in hyperoxic cultures, when normalized for cellular protein, but not DNA, was greater than normoxic values after 24 to 96 h of exposure. Unlike the decrease in cellular antioxidant enzymes during normoxic and hyperoxic culture, cellular LDH activity increased during both these exposures. Cellular LDH activity in 24 to 96 h hyperoxia-exposed cells increased to a lesser extent than normoxic controls. The extent of depression in LDH activity was dependent on whether the activity was normalized for cellular protein or DNA. Type II pneumocytes, which normally undergo hyperplasia and hypertrophy during hyperoxia in vivo, exhibited oxygen sensitivity in vitro. Exposure of type II cells to hyperoxia in vitro resulted in alterations in cellular SOD and LDH activities, but recognition of such changes were dependent on whether enzymatic activities were normalized for cellular DNA or protein.
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PMID:Responses of type II pneumocyte antioxidant enzymes to normoxic and hyperoxic culture. 250 12

Rats injected with interleukin-1 (10 micrograms) and tumor necrosis factor (10 micrograms) and then exposed continuously to hyperoxia (greater than 99% O2, 1 atm) survived longer, had increased lung reduced/oxidized glutathione ratios, smaller pleural effusions, less pulmonary hypertension and improved arterial blood gases. The percentage of animals surviving for 72 hours in hyperoxia increased from 8% to 94%. Although relatively small increases in glutathione redox cycle enzymes occurred four and sixteen hours following cytokine injection, dramatic increases in all major antioxidant enzymes including superoxide dismutase, glucose-6-phosphate dehydrogenase, glutathione reductase, glutathione peroxidase, and catalase had occurred following 72 hours of exposure to hyperoxia. The protective effect of IL-1 + TNF against lethal pulmonary O2 toxicity could be partially inhibited by pre-injection of lysine acetylsalicylate or, less effectively, of ibuprofen. Recent studies have suggested that both IL-1 and TNF can induce manganese (mitochondrial) superoxide dismutase mRNA and protein synthesis in a variety of cell types. Preliminary studies suggest that IL-1 alone, in ample dosage, can provide protection against lethal pulmonary O2 toxicity. Future studies should be directed toward identification of acute phase changes in lung antioxidant enzymes, surfactant proteins and/or lipid components, enzymes needed for synthesis of surfactant phospholipids, and/or other protective proteins. Additional work also needs to be done in identifying the lung cell types in which early enzyme induction occurs. These studies should provide a better understanding of mechanisms whereby protection against pulmonary O2 toxicity can occur. An understanding of the molecular mechanisms inducing protective proteins should lead to more precise pharmacologic control of these processes.
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PMID:Protection against pulmonary oxygen toxicity by interleukin-1 and tumor necrosis factor: role of antioxidant enzymes and effect of cyclooxygenase inhibitors. 251 82

Recent evidence supports the concept that Adriamycin cytotoxicity may be mediated by drug semiquinone free radical and oxyradical generation. We tested this hypothesis further by exposing drug-sensitive (WT) and 500-fold Adriamycin-resistant MCF-7 human breast tumor cells (ADRR) to exogenous superoxide- and hydrogen peroxide-generating systems and subsequently monitored cell proliferation as a measure of cytotoxicity. The ADRR tumor cells tolerated a 4-fold greater exposure than sensitive cells to superoxide generated by the xanthine/xanthine oxidase system. Likewise, exposure to hydrogen peroxide produced by the action of glucose oxidase on glucose revealed a 4-fold diminished susceptibility of the drug-resistant cells to this reduced form of oxygen. Similar results were obtained by the direct application of hydrogen peroxide to cells. For both cell lines, cytotoxicity was dependent upon the magnitude and the duration of reactive oxygen exposure. When WT and ADRR cells were cultured under hyperoxia (95% O2:5% CO2), in order to stimulate the intracellular production of oxyradicals, proliferation was inhibited to a greater extent in the drug-sensitive cell line. Additionally, hyperoxia potentiated the cytotoxicity of Adriamycin to both sensitive and drug-resistant cells, but the effect depended upon the concentration of the drug. Under hyperoxic conditions, Adriamycin caused oxygen radical-dependent cytotoxicity to the WT tumor cells at clinically relevant drug concentrations as low as 2 to 3 nM. With ADRR tumor cells, hyperoxia increased the cytotoxicity of Adriamycin at concentrations above 5 microM. Paradoxically, both the WT and the ADRR tumor cells were equally susceptible to the cytotoxic effects of gamma irradiation. It is known that the Adriamycin-resistant MCF-7 cells greatly overexpress glutathione peroxidase and glutathione transferase activities; however, other biochemical defenses against reactive drug intermediates and oxygen radicals have been reported to be similar in the two cell lines. We have reexamined those observations in this report. The resistance of ADRR breast tumor cells to Adriamycin appears to be associated with a developed tolerance to superoxide, most likely because of a twofold increase in superoxide dismutase activity, and a decreased susceptibility to hydrogen peroxide, most likely because of 12-fold augmented selenium-dependent glutathione peroxidase activity. Acting in concert, these two enzymes would decrease the formation of hydroxyl radical from reduced molecular oxygen intermediates.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Differential oxygen radical susceptibility of adriamycin-sensitive and -resistant MCF-7 human breast tumor cells. 253 95

When exposed continuously to hyperoxia (100% O2, 760 Torr barometric pressure), rats pretreated with polyethylene glycol (PEG)-attached superoxide dismutase and catalase (PEG-SOD + PEG-CAT) lived longer (79.1 + 7.6 h) than rats pretreated with saline (60.7 +/- 2.1 h) or PEG-inactivated-SOD + PEG-inactivated-CAT (62.3 +/- 1.6 h). Rats pretreated with PEG-SOD + PEG-CAT also had less hyperoxia-induced acute oxidative edematous lung injury, as assessed by increases in lung oxidized glutathione (GSSG) contents, pleural effusions, and lung lavage albumin concentrations than saline-pretreated rats. Rats pretreated with the long-lived conjugates PEG-inactivated-SOD + PEG-inactivated-CAT or PEG-albumin also had decreased acute oxidative edematous lung injury compared with rats pretreated with PEG, SOD + CAT + PEG, SOD + CAT, or saline. In vitro studies suggested that PEG itself may have contributed to protection by scavenging hydroxyl radical (.OH) but not superoxide (O2-.) or H2O2. Compared with more effective endogenous (via preexposure to hypoxia) or exogenous (via liposomes) means for increasing lung antioxidant enzymes, PEG enzymes are less protective against lung injury from continuous hyperoxia.
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PMID:Polyethylene glycol-attached antioxidant enzymes decrease pulmonary oxygen toxicity in rats. 254 Jan 39

We compared the superoxide anion generating capacity of subcellular fractions from the lungs of neonatal and adult rats. Microsomal and mitochondrial fractions from adult rats produced approximately three times more superoxide (nanomoles per minute per milligram protein) than fractions from neonatal rats in the presence of 100% O2. Subcellular superoxide anion generating capacity was also examined in adult and neonatal rats exposed to greater than 95% fractional concentration of O2 in inspired gas. The O2- produced by mitochondrial and microsomal fractions of adult and neonatal rats increased above control levels for the first 24 h and declined below control values after 48 h of exposure in adults, whereas the elevated O2- production was sustained in microsomal fractions of neonates through 60 h. During the course of hyperoxic exposure, the largest difference in the superoxide generating capacity between adult and neonate was observed after 8-24 h of hyperoxia. The microsomal and mitochondrial fractions from adult rats produced three to seven times more O2- compared with neonatal rats. Cu,Zn superoxide dismutase (SOD) increased during the course of hyperoxia only in neonates at 8, 24, and 48 h of exposure. No change was observed in the activity of Mn SOD. The ratio of SOD activity (units per lung) to subcellular superoxide generating capacity (nanomoles per minute per lung) was calculated for the normal adults and neonates. The ratio for adult rats averaged 23 and 17 for mitochondrial and microsomal fractions, respectively, and 51 for neonatal rats for both subcellular fractions under normoxic conditions. These results suggest that O2- tolerance of neonates may be explained by the favorable balance between antioxidant defenses and subcellular superoxide generating capacity. The role of increased activity of Cu,Zn SOD as an accompanying or a causative phenomenon in O2 tolerance of neonates could not be determined from these experiments.
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PMID:Oxygen tolerance in neonatal rats: role of subcellular superoxide generation. 255 83

1. During the development of D. pictus larvae (Amphibia) in normoxia, selenium (Se) GSH-Px increased whereas non-Se GSH-Px did not change. 2. Acclimation to 60 or 100% O2 did not change Se GSH-Px or non-Se GSH-Px. 3. Hyperoxia did not change tissue peroxidation (TBA-RS) confirming the good capacity of D. pictus tadpoles for O2-adaptation. 4. Since hyperoxic induction of catalase (CAT) has been previously described in D. pictus tadpoles, it is concluded that CAT is more important than both GSH-Px for the establishment of O2-adaptation. 5. Increases of Se GSH-Px, SOD and CAT, are probably important for adaptation to the change from aquatic to aerial environment during metamorphosis in normoxia. 6. Chronic exposure to 100% O2 enormously reduced the lung size of D. pictus larvae.
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PMID:Hyperoxia decreases lung size of amphibian tadpoles without changing GSH-peroxidases or tissue peroxidation. 256 23

Administration of endotoxin to adult rats increases lung Cu,Zn superoxide activity after 72 h of exposure to greater than 95% O2. The increased activity is brought about mainly by a faster rate of Cu,Zn superoxide dismutase synthesis; rats treated with endotoxin but not exposed to hyperoxia do not exhibit these findings (Hass, Frank, and Massaro, J. Biol. Chem. 257: 9379-9383, 1982). We now report that 48 h after treatment of adult rats with endotoxin there was a decreased rate of Cu,Zn superoxide dismutase synthesis by lung slices from air- and O2- exposed rats, although, in both groups, the lung concentration of Cu,Zn superoxide dismutase mRNA was increased approximately 45%. Exposure of endotoxin-treated rats to greater than 95% O2 or air for an additional 24 h (72 h all told) resulted in continued elevation of Cu,Zn superoxide dismutase mRNA only in lungs of O2- exposed rats. In vitro exposure of lung slices from air-breathing saline- or endotoxin-treated rats to 95% O2 for 6 h led to an increased rate of Cu,Zn superoxide dismutase synthesis only in slices from endotoxin-treated rats. We conclude that endotoxin treatment leads to an increased concentration of Cu,Zn superoxide dismutase mRNA in rat lungs, but a sustained elevation of the mRNA, and its translation into an increased rate of Cu,Zn superoxide dismutase synthesis requires exposure of the lung to hyperoxia.
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PMID:Endotoxin increases lung Cu,Zn superoxide dismutase mRNA: O2 raises enzyme synthesis. 256 34

A protective effect of butyrate against hyperoxia was found with adult rat pulmonary artery smooth muscle cells. Butyrate (5mM) when added just prior to the hyperoxic exposure (95%) markedly decreased lactate dehydrogenase release from cells during 68 hours of exposure (22% release with butyrate versus 98% without). The uptake and reduction of a tetrazolium compound as another index of cell viability also showed similar improvement with butyrate. Butyrate was associated with a striking increase of catalase to three times the control in the air exposed group while GSH content and the activities of superoxide dismutase and glutathione peroxidase were not significantly changed. In the groups exposed to hyperoxia alone, both enzyme activities were decreased compared to the air exposed controls. When butyrate was present with hyperoxia, the superoxide dismutase was maintained closer to the air exposed control values and the catalase activity remained nearly twice as high as the air exposed control cells. These results suggest that butyrate protects rat pulmonary artery smooth muscle cells from hyperoxia by increasing catalase activity which may help to preserve superoxide dismutase activity. This may be a good model to determine the biological significance of catalase and its interrelationships with other antioxidant systems within the cell.
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PMID:Butyrate increases catalase activity and protects rat pulmonary artery smooth muscle cells against hyperoxia. 259 Jan 95

Relative tolerance of newborn animals to hyperoxia has been reported. This study investigated the age limitation of oxygen tolerance and mechanisms for its loss. Developmental changes in lungs of normoxic New Zealand rabbits were studied on days 1, 3, 4, 5, and 10 of life. These were contrasted with newborn and 7-day-old rabbits exposed to greater than 95% O2 for 65 hours. Normoxic rabbits demonstrated a decrement in bronchoalveolar lavage (BAL) 6keto-PGF1a, thromboxane B2, and lower lung catalase, total glutathione, and superoxide dismutase with maturation. Newborns were more tolerant to oxygen than 7-day-old rabbits. Oxygen exposure beginning on day 1 did not result in identifiable lung damage. Exposure beginning on day 7 resulted in microscopic evidence of injury and significant increases in BAL white cells, neutrophils and protein, and a trend toward higher BAL LTB4 compared to normoxic age-matched controls. Antioxidants were higher in the hyperoxic 7 day-olds, but remained lower than values in hyperoxic newborns. These results suggest that loss of oxygen tolerance in maturing rabbits is related to a developmental decrement in antioxidants and prostacyclin.
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PMID:Loss of oxygen tolerance in newborn rabbits: relationship to changes in eicosanoid and antioxidant levels. 261 44

Rhodotorula mucilaginosa is an obligate aerobic yeast which contains a high concentration of carotenoid pigment. To test whether carotenoids are able to protect R. mucilaginosa against oxidative injury, yeast cells in liquid culture were incubated with duroquinone (DQ) (100 microM), a redox-cycling quinone known to generate intracellular O2-. or were grown in a hyperoxic atmosphere (80% O2) under conditions where carotenoid concentrations were altered either intracellularly or extracellularly. Neither of these oxidative challenges affected cell growth unless carotenogenesis was blocked by the addition of diphenylamine (50 microM). In the diphenylamine-treated nonpigmented cells, growth was completely inhibited by DQ and by hyperoxia. In normoxia, however, diphenylamine alone reduced growth by only 30%. The growth inhibition observed in diphenylamine-treated cells exposed to hyperoxia was primarily mycocidal rather than mycostatic since plating of these cells onto solid media revealed that only 25% of the cells were viable after 50 h of incubation when compared to plated control cells. Addition of 10 microM beta-carotene to diphenylamine-treated cells completely prevented the growth inhibition caused by either hyperoxia or DQ. Carotenoids, therefore, are able to prevent oxidant-induced cytotoxicity in R. mucilaginosa. Analysis of the absorption spectra of chloroform extracts of beta-carotene-supplemented cells showed that beta-carotene, not the endogenous carotenoid, torularhodin, was the major carotenoid present in these cells. Superoxide dismutase (SOD) activity in R. mucilaginosa was compared with that of another yeast, Saccharomyces cerevisiae by two methods: (i) activity staining of proteins separated by gel electrophoresis and (ii) measurement of inhibition of ferricytochrome c reduction. By these techniques, the R. mucilaginosa SOD activity had the characteristics of Mn-SOD. No Cu/ZnSOD activity was detected. Thus, the apparent absence of Cu/ZnSOD may make the antioxidant capability of endogenous carotenoids even more critical in preventing oxidative damage in R. mucilaginosa.
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PMID:The role of carotenoids in preventing oxidative damage in the pigmented yeast, Rhodotorula mucilaginosa. 265 Jun 23


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