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

Preexposure of rats to sublethal levels of hyperoxia or ozone reduces morbidity and mortality when the animals are subsequently exposed to lethal levels of either oxidant stress. Lung homogenates and isolated type II pneumocytes from rats exposed to these oxidant stresses demonstrate enhanced antioxidant enzyme activities. Antioxidant enzymes, superoxide dismutase, catalase, and glutathione peroxidase are responsible for the detoxification of partially reduced oxygen species, superoxide and hydrogen peroxide, to less reactive states. Potential pulmonary cellular loci of partially reduced oxygen include mitochondrial NADH dehydrogenase, endoplasmic reticulum-derived NADPH cytochrome c reductase, and cytosolic xanthine oxido reductase. Thus partially reduced oxygen species are hypothesized to mediate hyperoxia and ozone-induced pulmonary damage. This damage may be attenuated by enhanced intracellular antioxidant enzyme activities. Pharmacologic augmentation of pulmonary antioxidant enzymes may be accomplished via intratracheal or intravascular delivery of liposomes containing antioxidant enzymes. Rats pretreated with liposomes containing both superoxide dismutase and catalase, when subsequently exposed to lethal levels of hyperoxia, demonstrate enhanced survival compared with control animals or with animals treated with control liposomes or native antioxidant enzymes. Finally, knowledge obtained from in vitro investigations optimizing liposomal delivery to specific pulmonary cell types may further aid in reducing in vivo pulmonary damage to hyperoxia and ozone.
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PMID:Pulmonary metabolism of reactive oxygen species. 306 93

This study evaluated the effect of hyperoxia on the pharmacokinetic function of the lung. Hyperoxia is known to disrupt the activities of the pulmonary prostaglandin dehydrogenase/reductase and angiotensin converting enzymes. This would be predicted to alter the activation/deactivation of prostaglandins or angiotensin. The ability of these enzyme systems to act upon these compounds was evaluated by measuring the changes in the peripheral vascular responses to exogenous prostaglandin and angiotensin. Two groups of conscious, chronically catheterized rabbits, one exposed to ambient air and the other to greater than 98% oxygen, were given bolus injections of angiotensin I, angiotensin II, prostaglandin E2, sodium nitroprusside, and phenylephrine before and during up to 88 h of air or oxygen exposure. The hyperoxic animals' responsiveness to angiotensin I and angiotensin II decreased by 47% and 55%, respectively, after 72 h of oxygen exposure. The hyperoxic animals demonstrated a 54% increase in the vasodilatory response to arterial prostaglandin E2. Normoxic rabbits demonstrated no changes in response to any of the compounds tested. These data indicate that chronic hyperoxia influences either the synthesis/degradation and/or vascular receptors to both angiotensin I and II and prostaglandins.
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PMID:Effects of chronic hyperoxia on the cardiovascular responses to vasoactive compounds in the rabbit. 316 78

Hyperoxia has been shown to disrupt certain membrane bound enzyme systems within the pulmonary endothelium which are responsible for the metabolism of several endogenous vasoactive compounds. This study was to evaluate whether the potential disruption of the prostaglandin dehydrogenase/reductase and angiotensin converting enzymes, as a consequence of hyperoxia, would alter the activation/deactivation of prostaglandins or the angiotensins (I and II) and thereby alter their peripheral cardiovascular actions. Two groups of anesthetized dogs, one group ventilated with ambient air and the other with 100% oxygen, were given bolus injections of angiotensin I, angiotensin II, prostaglandin E2, sodium nitroprusside, and phenylephrine before and during 8 h of exposure to air or oxygen. The hyperoxic animals demonstrated a significant increase in mean arterial pressure responsiveness to both angiotensin I and angiotensin II. The responsiveness to the drugs increased by 41% for angiotensin I and 43% for angiotensin II. The ambient air control dogs showed no significant changes for any compounds tested. These data indicate that with 8 h of hyperoxia the renin-angiotensin system's ability to influence cardiovascular function is augmented, whereas, the hemodynamic effects of prostaglandins are unaltered.
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PMID:Effects of 100 percent oxygen on the cardiovascular responses to vasoactive compounds in the dog. 386 38

Weanling male rats were fed semi-purified diets supplemented with 0, 60, or 600 IU X g-1 vitamin E or 0, 100 or 1000 ppb selenium. One group was injected daily with vitamin E at a rate equivalent to consumption of 60 IU X kg-1. Animals from all groups were sacrificed after exposure to normobaric oxygen or air for 48 h. Lung tissue was analyzed for the combined activity of prostaglandin dehydrogenase and reductase. Using the decline in enzyme activity as an indicator of susceptibility to oxygen poisoning, protection against hyperoxia was directly related to the level of vitamin E supplementation. Selenium supplemented at 100 ppb provided significant protection when compared to 0 ppb or 1000 ppb. The latter dose may have been marginally toxic. We conclude that dietary supplementation of vitamin E and selenium may influence the relative susceptibility of an animal to pulmonary oxygen poisoning.
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PMID:Effect of dietary vitamin E or selenium on prostaglandin dehydrogenase in hyperoxic rat lung. 608 85

Prostaglandin metabolism by rat lung tissue was measured following exposures of 6, 24 and 48 hours to either pure oxygen or air at one atmosphere. Tissue concentrations of PGE1, PGE2 and PGF2 alpha were not altered by oxygen exposures. Prostaglandin synthetase activity decreased between 24 and 48 hours but was not significantly different from control at 48 hours. Combined prostaglandin dehydrogenase/reductase activity decreased between 24 and 48 hours to 13% of control values and was significantly lower than in air at 48 hours. The plasma concentration of 13, 14 dihydro-15-keto PGF2 alpha, a catabolite of PGF2 alpha, was significantly lower in oxygen-exposed rats at 24 and 48 hours. We conclude that endogenous pulmonary prostaglandin concentrations are maintained during hyperoxia but that catabolism of prostaglandins by the lungs may be impaired.
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PMID:Pulmonary prostaglandin metabolism during normobaric hyperoxia. 626 Dec 83

Weanling male rats were fed a semi-purified diet containing 10, 20, 40 or 60% of calories as fat having a constant polyunsaturated/saturated fatty acid ratio of 0.7. After 21-28 d of feeding, animals from each treatment group were exposed to pure oxygen at one atmosphere absolute for up to 72 h. Some animals were sacrificed after 0 or 48 h of oxygen exposure and lung tissue analyzed for the activities of the hexose monophosphate shunt and prostaglandin dehydrogenase/reductase. Other animals were exposed to hyperoxia until death. With increasing dietary fat content, the pre-exposure activities of the two enzymes decreased and oxygen-induced mortality increased. There was no dietary effect on enzyme activities after 48 h of hyperoxia. We concluded that both dietary fat content and the pre-exposure activity of prostaglandin dehydrogenase/reductase influenced the relative susceptibility to pulmonary oxygen poisoning.
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PMID:Effect of dietary fat on pulmonary enzymes and toxicity during normobaric hyperoxia. 711 50

Depletion of glutathione, a key antioxidant, accelerates lung injury. Glutathione concentrations are reduced significantly in premature infants with respiratory distress syndrome, leaving them at greater risk of bronchopulmonary dysplasia. A study was designed to verify if the increased glutathione synthetic activity observed in oxygen-dependent and ventilated newborn infants was caused by their postsurgical state. Our objective was to evaluate the role of a general surgical procedure as a factor affecting lung glutathione. One-day-old guinea pig pups, a well characterized animal model for the study of neonatal lung disease, were divided between those undergoing a standardized surgical procedure and those that did not. The pups were fed by their mother. After 4 days the lungs were sampled to determine total glutathione content, activities of gamma-glutamyltranspeptidase, glutathione peroxidase, and reductase as well as the glutathione synthetic activity. The surgical procedure was associated with a specific stimulatory effect limited to glutathione synthetic activity (p < 0.02) leading to an increased (p < 0.02) pulmonary glutathione content. Glutathione concentration was significantly correlated (r2 = 0.67) with the synthetic activity. We concluded that in this animal model an invasive procedure such as a general surgical procedure affects lung glutathione metabolism in a fashion similar to that of hyperoxia. In the lungs, the synthetic activity is a stronger determinant of glutathione concentrations than the activities of the other enzymes involved in maintaining glutathione levels.
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PMID:Glutathione synthetic activity in the lungs in newborn guinea pigs. 983 29

Thioredoxin (TRX) is a potent protein disulfide oxidoreductase important in antioxidant defense and regulation of cell growth and signal transduction processes, among them the production of nitric oxide. We report that lung TRX and its reductase, TR, are specifically upregulated at birth by O2. Throughout the third trimester, mRNAs for TRX and TR were expressed constitutively at low levels in fetal baboon lungs. However, after premature birth (125 or 140 of 185 days gestation), lung TRX and TR mRNAs increased rapidly with the onset of O2 or air breathing. Lung TRX mRNA also increased in lungs of term newborns with air breathing. Premature animals (140 days) breathing 100% O2 develop chronic lung disease within 7-14 days. These animals had greater TRX and TR mRNAs after 1, 6, or 10 days of life than fetal control animals. In 140-day animals given lesser O2 concentrations (as needed) who do not develop chronic lung disease, lung TRX and TR mRNAs were also increased on days 1 and 6 but not significantly on day 10. In fetal distal lung explant culture, mRNAs for TRX and TR were elevated within 4 h in 95% O2 relative to 1% O2, and the response was similar at various gestations. In contrast, TRX protein did not increase in lung explants from premature animals (125 or 140 days) but did in those from near-term (175-day) fetal baboons after exposure to hyperoxia. However, lung TRX protein and activity, as well as TR activity, eventually did increase in vivo in response to hyperoxia (6 days). Increases in TRX and TR mRNAs in response to 95% O2 also were observed in adult baboon lung explants. When TRX redox status was determined, increased O2 tension shifted TRX to its oxidized form. Treatment of lung explants with actinomycin D inhibited TRX and TR mRNA increases in 95% O2, indicating transcriptional regulation by O2. The acute increase in gene expression for both TRX and TR in response to O2 suggests an important role for these proteins during the transition from relatively anaerobic fetal life to O2 breathing at birth.
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PMID:Induction of thioredoxin and thioredoxin reductase gene expression in lungs of newborn primates by oxygen. 1007 Jan 19

Exposure of adult male rats to hyperoxia (O(2) > 95%) resulted in a tendency for all of the components of the pulmonary cytochrome P450 (P450) system to increase at 48 h after the exposure. However, the most pronounced effect of hyperoxia was observed on pulmonary ethoxycoumarin O-deethylase and ethoxyresorufin O-deethylase activities which were induced 4- and 25-fold respectively after 48 h. In the liver, P450 and NADH b(5) reductase were increased after 48 h, while other components of the monooxygenase system remained unchanged. In the hepatic microsomes, contrary to the lungs, aminopyrine N-demethylase activity was decreased after 24 h of hyperoxic exposure (P < 0.05) and returned to the control level by 48 h. Similar changes were observed in benzphetamine N-demethylase activity. Aniline hydroxylase activity was decreased after 8 h of hyperoxic exposure (P < 0.01) and remained decreased at 24 h (P < 0. 01) and 48 h (P < 0.05). The level of induction of ethoxycoumarin O-deethylase and ethoxyresorufin O-deethylase activities, however, was almost similar in the liver to that observed in the lungs.
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PMID:Effect of hyperoxia on rat pulmonary and hepatic cytochrome P450 monooxygenases. 1066 85

In many models, a protective role for heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme degradation, has been demonstrated. Also, HO-1 null mice (KO) are more susceptible to inflammation and hypoxia and transplant rejection. Nonetheless, their response to hyperoxia (> 95% O(2)) has not yet been evaluated. Surprisingly, after acute hyperoxic exposure, KO had significantly decreased markers of lung oxidative injury and survived chronic hyperoxia as well as wild-type (WT) controls. Disrupted HO-1 expression was associated with decreased lung reactive iron and iron-associated proteins, decreased NADPH cytochrome cp450 reductase activity, and decreased lung peroxidase activity compared to WT. Injection of tin protoporphyrin, an inhibitor of HO, in the WT decreased acute hyperoxic lung injury, whereas transduction of human HO-1 in the KO reversed the relative protection of the KO to acute injury and worsened hyperoxic survival. This suggests that disruption of HO-1 protects against hyperoxia by diminishing the generation of toxic reactive intermediates in the lung via iron and H(2)O(2).
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PMID:Resistance to hyperoxia with heme oxygenase-1 disruption: role of iron. 1249 87


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