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

Adult rats show evidence of severe lung damage after 72h of continuous exposure to hyperoxia (96-98% O2). Treatment of adult rats with a solution of Plasmanate, inadvertently contaminated with endotoxin-producing organisms, or with purified endotoxin itself markedly altered the lung toxicity associated with hyperoxic exposure (survival in treated animals = 110/113 [97%] versus survival in untreated animals = 56/172 [33%]). After 72h of hyperoxic exposure, the endotoxin-treated rats demonstrated significant increases in lung superoxide dismutase, catalase, and glutathione peroxidase activity, a protectant enzyme response not seen in untreated adult rats. The basis for endotoxin's protective effect from hyperoxic lung damage is believed to be related to the stimulated increase in activity of the pulmonary antioxidant enzyme defense system. Some previously known actions of endotoxin are speculated to also serve a protective function by opposing some of the usual detrimental effects of high concentrations of O2 on the lung.
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PMID:The role of endotoxin in protection of adult rats from oxygen-induced lung toxicity. 62 Dec 74

Neonatal and adult animals of five species were exposed to 95+% O2. Survival time and changes in lung antioxidant enzyme activity (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GP)) in response to hyperoxia were determined. Adult animals succumbed to O2 lung toxicity in 3--5 days. Neonatal rats, mice and rabbits showed minimal lung changes after 7 days of hyperoxic exposure and these same neonatal animals showed rapid and significant increases in lung antioxidant enzyme activities. In contrast, neonatal guinea pigs and hamsters had no lung antioxidant enzyme response to hyperoxia and these neonates died in 95+% O2 as readily as their respective parent animals. Results from an in vitro hyperoxic exposure system suggest that the lack of enzymic response of the guinea pig (and hamster) neonates to O2 challenge is due to an inherent pulmonary biochemical unresponsiveness rather than to a deficiency of a necessary "serum factor." The results of this species and age study support the important role of the lung antioxidant enzyme defense system in protection of the lung from O2-induced injury.
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PMID:Oxygen toxicity in neonatal and adult animals of various species. 73 May 65

Undernutrition may exacerbate hyperoxia-induced lung injury, a finding that may be of significance in the early clinical management of the premature human infant. Addressing this specific problem, we found that 72 h of food restriction in guinea pig pups delivered 3 days preterm increased mortality rates among pups exposed to 95% oxygen (8/18) and yet had no effect on 21% oxygen (air)-exposed pups (0/10). Reduced tolerance of hyperoxic conditions was not, however, associated with increased lung injury, assessed as pulmonary microvascular leakage. Pulmonary antioxidant enzyme activities [Cu,Zn superoxide dismutase (SOD), Mn SOD, glutathione peroxidase, and catalase] were unaltered by starvation or hyperoxia. Lung glutathione concentration was slightly decreased after food restriction, whereas hyperoxic exposure did not change either lung or bronchoalveolar lavage fluid glutathione concentrations or lung antioxidant enzyme activities. Increased susceptibility to the lethal effects of oxygen in the starved preterm guinea pig pup could not be attributed to a deficiency of pulmonary antioxidant defenses.
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PMID:Effect of food restriction on hyperoxia-induced lung injury in preterm guinea pig. 141 61

Newborn rats prenatally treated with TRH or the combination of TRH + DEX have lower lung antioxidant enzyme activities at birth than control newborns but are able to induce an adaptive antioxidant enzyme response to hyperoxic exposure of similar or even greater magnitude compared to O2 control offspring. Because of this greater antioxidant enzyme response, we hypothesized that the hormonally pretreated newborns might demonstrate superior tolerance to prolonged high O2 exposure. However, when placed in greater than 95% O2 at birth, the survival rates were consistently lower in the TRH- and TRH + DEX-treated pups at all time periods in hyperoxia from 9 d [control = 74 of 92 (80%); TRH + DEX = 32 of 47 (68%); TRH = 29 of 48 (60%); p less than 0.05] to 14 d [control = 43 of 92 (47%); TRH + DEX = 11 of 47 (23%); TRH = nine of 48 (19%); (p less than 0.05)]. Other evidence of poorer O2 tolerance in the prenatal hormone-treated pups included a greater incidence of intraalveolar edema and elevated lung conjugated dienes, an index of lipid peroxidation, at 3, 5, and 7 d of O2 exposure. There was also a persistent elevation in 3,5,3'-triiodo-L-thyronine and thyroxine serum levels in the 10-d-old TRH-treated offspring. We conclude that prenatal TRH treatment, possibly working through the secretion of 3,5,3'-triiodo-L-thyronine and thyroxine, has some important lasting postnatal effect (not completely reversed by dexamethasone) that predisposes newborn rats to greater O2 radical-induced lung sequelae of prolonged hyperoxic exposure.
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PMID:Prenatal thyroid releasing hormone and thyroid releasing hormone plus dexamethasone lessen the survival of newborn rats during prolonged high O2 exposure. 143 92

An in vitro model of alveolar epithelial oxidant injury was developed based on exposure to hyperoxia of cultured guinea pig type II pneumocytes using a biphasic cell culture system in aerobiosis. The present study investigates the roles of intracellular antioxidant enzymes and of glutathione in providing protection against hyperoxia. A 2-day type II cell culture in normoxia was associated with a significant decrease in protein, catalase, and Cu-Zn SOD cell content, whereas ATP cell content, Mn-SOD, and glutathione peroxidase (GPx) activities did not change and glutathione cell content significantly increased. Exposure of type II cells to hyperoxia did not induce significant changes in cell content in protein, SOD, catalase, GPx, or glutathione cell content when compared to control cells (exposed to normoxia). With ATP cell content expressed as a cell injury index (CII), type II cell injury was found to increase with increasing O2 concentrations. Indeed, a 2-day 50% O2 and 95% O2 exposure resulted in a CII of -7.5 +/- 6.2% and 17.9 +/- 5.9%, respectively, LDH release by type II cells was not significantly increased after hypoxic exposure. Cell injury effects of hyperoxia did not correlate with the endogenous antioxidant enzyme activities (SOD, Mn-SOD, catalase). In marked contrast, there was a significant correlation between the CII and total glutathione content of type II cells (p < .01). This correlation was largely due to the close relationship between CII and reduced glutathione. Hyperoxic induced cell injury (as demonstrated by CII > 0) was clearly associated with significantly lower intracellular glutathione level when compared to experiments without hyperoxia induced cell injury (CII < 0). In addition, in the presence of buthionine sulfoximine (BSO), the ability of type II cells to synthetize new glutathione was severely impaired, whereas ATP cell content and cell antioxidant enzyme activities did not change. As a consequence, the reduction of intracellular glutathione significantly increased the susceptibility of cells to hyperoxia injury (p < .05). The results strongly support the hypothesis that the regulation of glutathione levels is an important mechanism in protecting hyperoxia-induced type II cell injury.
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PMID:In vitro effects of hyperoxia on alveolar type II pneumocytes: inhibition of glutathione synthesis increases hyperoxic cell injury. 146 13

Prenatal dexamethasone (DEX) treatment is known to accelerate the maturation of both the surfactant system and the fetal lung antioxidant enzyme (AOE) system (Frank L, Lewis P, Sosenko IRS: Pediatrics 75:569-574, 1985). Because of this stimulatory effect of prenatal DEX on the normal late gestational development of the AOE system, we questioned whether this treatment might have a salutary effect on the ability of the newborn rat to tolerate early and prolonged exposure to hyperoxia, inasmuch as the AOE are the primary lung defensive system against high O2 challenge. In nine experiments with term newborn rats in greater than 95% O2, the composite percentage of survival was significantly greater in the prenatal DEX pups at all time periods in hyperoxia from 7 d [control pups, 67 of 94 (71%); prenatal DEX, 96 of 99 (97%)] to 14 d [controls, 10 of 32 (31%); prenatal DEX, 18 of 33 (55%)] (p less than 0.01). In addition to survival per se, the prenatal DEX pups showed significantly decreased lung wet weight/dry weight ratios, pathologic evidence of pulmonary edema, and lung conjugated dienes versus the O2 control newborn group. Of the many comparative parameters examined, the major difference found between the two groups was in the pulmonary AOE responses to hyperoxia. By 2 d in hyperoxia, the prenatal DEX rat pups showed significantly elevated superoxide dismutase, catalase, and glutathione peroxidase activities compared to air control pups, and at 4 and 7 d in O2 the AOE levels were consistently greater in the DEX group than the AOE responses in the control O2 pups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prenatal dexamethasone treatment improves survival of newborn rats during prolonged high O2 exposure. 150 13

Bacterial endotoxin has been shown to protect rats from lethal hyperoxia. The structure of endotoxin contains diphosphoryl lipid A (DPL) as the lipid backbone stripped of protein and polysaccharides. DPL is the component of the endotoxin molecule that has been demonstrated (in previous studies) to be responsible for the immunologic, mitogenic, pyrogenic, and lethal properties of endotoxin. Monophosphoryl lipid A (MPL) is a nonpyrogenic, nontoxic modification of the DPL molecule that retains its immunostimulatory and mitogenic properties. We hypothesized that DPL may be the actual active component of endotoxin that protects rats from lethal hyperoxia. We also hypothesized that the protection from hyperoxia that is afforded by the DPL component may be related to endogenous release of tumor necrosis factor alpha which should allow MPL to also be protective. To test these hypotheses, we performed a series of experiments in which rats were treated with endotoxin, DPL, MPL or vehicle and exposed to room air or hyperoxia. We found that DPL and endotoxin both protected rats from lethal hyperoxia, but MPL alone was not protective. Even though MPL was not protective, DPL and MPL both increased endogenous release of tumor necrosis factor alpha early after injection (peak DPL level, 3619 +/- 1500 pg/ml, peak MPL level, 4038 +/- 500 pg/ml). Protection in both the endotoxin- and DPL-treated animals was associated with increases in lung antioxidant enzyme activities. We concluded that DPL protect rats from hyperoxia but that MPL is not protective in spite of its immunostimulatory and mitogenic effects.
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PMID:Diphosphoryl lipid A protects rats from lethal hyperoxia. 151 89

Neonatal animals of several species are more tolerant of hyperoxic exposure than are adults, but the mechanisms of increased neonatal tolerance are unknown, as are the cell types, if any, that contribute to oxygen resistance. We studied the effect of in vivo exposure to 85% oxygen for 72 h on the activities of the antioxidant enzymes, glutathione peroxidase, catalase and superoxide dismutase (SOD), in alveolar type II cells and whole lung from adult and neonatal rats. Baseline antioxidant enzyme activities were generally lower in neonatal type II cells compared with adults. Baseline enzyme activities did not differ in neonatal type II cells and lung homogenates except for lower catalase activity in type II cells. Hyperoxic exposure resulted in 35-38% increases in antioxidant enzyme activities in neonatal whole lung. In neonatal type II cells, SOD activity increased by 170% after hyperoxia, whereas catalase and glutathione peroxidase were not significantly changed. In the adult whole lung, hyperoxic exposure resulted in increases in only glutathione peroxidase activity, whereas in adult type II cells there was a significant decrease in SOD activity after O2 exposure. Therefore, although baseline antioxidant enzyme activities were not higher in neonatal type II cells compared with whole lung, there were differences in the antioxidant enzyme responses of adult and neonatal type II cells to hyperoxia, particularly with respect to SOD. The ability of the neonatal type II cell to respond to hyperoxia with an early increase in SOD activity may contribute to the enhanced oxygen tolerance of the neonate.
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PMID:The effect of hyperoxic exposure on antioxidant enzyme activities of alveolar type II cells in neonatal and adult rats. 160 20

HA-1 hamster fibroblasts receiving fresh media every 24 h were continuously passaged in progressively increasing O2 concentrations for 18 mo (designated O2R95). These cells were significantly more resistant than parental HA-1 to clonogenic inactivation mediated by 95% O2 without media replacement. The O2R95 cell line exhibited increases in the activities of catalase (CAT), Mn superoxide dismutase (MnSOD), Cu,Zn superoxide dismutase (Cu,Zn SOD), and glutathione peroxidase (GPx). O2R95 cells demonstrated uniformly distributed increased staining for CAT, MnSOD, Cu,Zn SOD, and GPx proteins, as determined by immunohistochemistry. Cellular resistance to and metabolism of 4-hydroxy-2-nonenal (4HNE), a toxic byproduct of lipid peroxidation implicated in mechanisms of O2 toxicity, was examined in HA-1 and O2R95 cell lines. O2R95 cells were significantly more resistant to 4HNE cytotoxicity, which was accompanied by a significant increase in 4HNE metabolism. O2R95 cells also demonstrated an increase in total glutathione (GSH) and glutathione S-transferase (GST) activity, an enzymatic system believed to be involved with 4HNE metabolism. Furthermore, homogenates from O2R95 cells consumed greater quantities of 4HNE in the presence of NADPH (but not NADH, NAD+, or NADP+), suggesting that an enzyme(s) utilizing NADPH contributes to 4HNE metabolism, resistance to 95% O2 and 4HNE as well as increased total GSH, antioxidant enzyme activities, and NADPH-dependent metabolism of 4HNE, persisted in O2R95 cells for 75 days of growth in 21% O2. These findings are compatible with the hypothesis that aldehydic byproducts of lipid peroxidation contribute to mechanisms of O2 toxicity and the selective pressure exerted by exposure of cells to hyperoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A stable O2-resistant cell line: role of lipid peroxidation byproducts in O2-mediated injury. 161 58

Air-breathing organisms experience an elevated concentration of oxygen mainly under two conditions. One occurs at birth when the O2 tension in the lung increases from approximately 25 torr present in utero to approximately 100 torr. The lungs, in particular, are also exposed to hyperoxia when oxygen is administered for therapeutic reasons. Under hyperoxic conditions, increased lung antioxidant enzyme activity is important for survival. The molecular basis for the increase in antioxidant enzyme gene expression under these circumstances is not well understood; in hyperoxia-exposed neonatal rats the elevation of lung catalase activity is not due to an increased rate of transcription but is associated with an increased concentration of catalase mRNA due to enhanced stability of the mRNA (Clerch, L.B., Iqbal, J., and Massaro, D. (1991) Am. J. Physiol. 260, L428-L433). We now show that neonatal rat lung protein forms specific complexes with catalase mRNA; this binding is redox-sensitive since when oxidizing agents are added binding is abolished but is restored by reducing agents. Our data also indicate lungs from hyperoxia-exposed rats have a larger proportion of catalase RNA-binding protein in oxidized form than lungs from air-breathing rats. This redox-sensitive binding of protein to catalase mRNA may be important in the control of catalase gene expression.
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PMID:Oxidation-reduction-sensitive binding of lung protein to rat catalase mRNA. 173 43


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