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

Alterations in activity of cholesterol esterases from lysosomal, microsomal and cytoplasmic cell fractions of rat liver tissue were studied under conditions of acute and chronic hypoxia and hyperoxia. Activity of the membrane-bound lysosomal and microsomal cholesterol esterases was decreased but the cytoplasmic enzyme was activated in acute hypoxia and hyperoxia. These data suggest that the enzymes, responsible for alterations in the ratio free cholesterol/cholesterol esters in cells, are dependent on the level of oxygen consumption.
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PMID:[Effect of changes in the oxygen level on cholesterol esterase activity of the liver of intact rats and rats subjected to chronic hypoxia]. 409 Mar 88

A previous report from this laboratory (Bender, D.A., Magboul, B.I. and Wynick, D. (1982) Brit. J. Nutr. 48, 119-127) suggested that the hydrolysis of the nicotinamide nucleotides NAD and NADP may be an important factor in controlling the tissue content of these coenzymes. Further studies presented here support this suggestion. Both nuclear poly(ADPribose) synthetase and microsomal NAD glycohydrolase showed activity towards both NAD+ and NADP+, and the two nucleotides were mutually competitive. The reduced nucleotides, NADH and NADPH, were not substrates for either enzyme. In rats that were maintained for 24 h under conditions of hypoxia (O2/N2, 1:9) there was an increase in the proportion of nicotinamide nucleotides present in the liver in the reduced form, and an increase in the total concentration of nucleotides in the liver. In rats that were maintained for 24 h under conditions of hyperoxia (O2/N2, 7:3) there was no change in either the proportion of nicotinamide nucleotides in the liver present in the reduced form or in the total tissue control of the nucleotides. There was an increase in the urinary excretion of kynurenine suggesting an increase in the oxidative metabolism of tryptophan.
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PMID:The role of catabolism in controlling tissue concentrations of nicotinamide nucleotide coenzymes. 630 51

Hyperbaric oxygen (HPO) was administered to rats (100% O2 at 2.8 atm for 90 min) immediately or 1 hr after severe carbon tetrachloride (CCl4) intoxication in order to study the mechanisms of protection against hepatocellular injury by hyperoxia. Slight to moderate hepatocellular injury was observed, particularly by morphologic criteria, 4 hr after CCl4 intoxication. Little cell death was observed; 24 hr after CCl4, 20% of the untreated animals died. In the survivors, the following typical changes occurred in the liver: extensive hepatocellular swelling, vacuolization and necrosis; severe ultrastructural alterations; binding of CCl4 to microsomal lipids; elevation of lipid peroxidation products (conjugated dienes); little decrease in cytochrome b5 and severe decrease in cytochrome P-450 levels. Serum transaminase (alanine aminotransferase and aspartate aminotransferase) levels were elevated. Immediate treatment with HPO prevented the mortality and markedly decreased the hepatocellular necrosis 24 hr after intoxication. Immediate HPO treatment did not lower the levels of free CCl4 in the liver. However, the rise in lipid peroxidation products caused by CCl4 intoxication at 4 hr was reduced. Delayed treatment with HPO (1 hr after CCl4) prevented the mortality but was less effective in preventing necrosis. Some hepatocellular protection was still demonstrable. In particular, the rise in lipid peroxidation products was reduced. Hyperoxia protects hepatocytes against CCl4 toxicity. The rapid decline in protective effect within 60 min of intoxication suggests that hyperoxia inhibits CCl4 activation and/or damage from molecular intermediates. Hyperoxia has little effect on the progression of sublethal injury to cell death in the livers of CCl4-intoxicated rats.
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PMID:Protection of hepatocytes with hyperoxia against carbon tetrachloride-induced injury. 653 53

Interferon inducers, poly I:poly C, endotoxin, hepatic RNA, and Tilorone, were administered to rats at different time points in relation to the onset of hyperoxic exposure (O2 greater than 97%). All interferon inducers tested significantly reduced the mortality of rats when compared with the control groups. In hyperoxia alone, malondialdehyde, a product of lipid peroxidation, was significantly increased and the microsomal enzyme NADPH cytochrome c reductase decreased as measured in the whole lung. With the administration of either endotoxin or poly I:poly C these two parameters remained within the range of control values. These data suggest that the administration of interferon inducers protects against hyperoxic microsomal damage. After the administration of these interferon inducers with or without hyperoxia the increased activity of heme oxygenase and marked reduction of the heme content of microsomes were demonstrated. Since cytochrome P-450 and b5 are the major hemoproteins of microsomes and the known source of oxygen-free radical generation, the results obtained in this study appear to indicate that the depression of the hemoprotein of microsomes by the administration of interferon inducers may be largely responsible for the protective effects of these agents against hyperoxia.
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PMID:Protective effect of interferon inducers against hyperoxic pulmonary damage. 654 2

The efficacy of niacin in protecting rats from normobaric hyperoxia was evaluated in vivo by exposing niacin treated animals and controls to greater than 95% O2 for 96 hours. The vitamin was also evaluated as a possible free radical scavenger in vitro using an Fe-ascorbate initiated microsomal lipid peroxidation system. No protective effects were observed in vivo either in mortality or in differences in lung wet and dry weights of the niacin treated rats when compared to controls. Niacin in varying concentrations also did not decrease lipid peroxidation in the microsomal systems. Although this vitamin has been reported to protect animals from paraquat toxicity when given intraperitoneally once daily, niacin administered in similar doses does not appear to protect rats from hyperoxia.
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PMID:Inability of niacin to protect from in vivo hyperoxia or in vitro microsomal lipid peroxidation. 718 25

We hypothesized that during a critical neonatal period hyperoxia may produce alterations of sex-specific cytochrome P450 isozymes in adulthood (enzyme imprinting). To test this, newborn rats were exposed to 24 or 72 h of hyperoxia (O2 > 95%) within 24 h after birth and killed at 120 d. In males, significant negative imprinting (decrease) was found in total cytochrome P450 content and male-specific CYP2C11 in the hyperoxia groups. Positive imprinting (increase) was noted in CYP1A2 and male-specific CYP3A2 in the 72-h hyperoxia group. These alterations were essentially similar when expressed on a per microsomal protein or per liver basis. In addition, the level of hepatic glucocorticoid receptor in adult male rats was elevated after neonatal hyperoxia. In females, there was a significant body and liver weight loss after hyperoxic exposure, which resulted in a negative imprinting of CYP1A2 and female-specific 2C12 in the 72-h hyperoxia group on a per liver basis, whereas the measured parameters were unaltered when expressed per microsome. In general, the changes were more marked with longer hyperoxic exposure, suggesting that more pronounced alterations may be induced with prolonged neonatal hyperoxia. Because hyperoxic exposure in premature neonates is a common clinical practice and decreased CYP2C11 in adult males is expected to result in feminization, we believe that the scope of this work should be expanded and eventually tested for its relevance in human subjects.
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PMID:Neonatal hyperoxia and cytochrome P450 imprinting in adulthood. 816 63

Hepatic dysfunction is a major contributor to death in multiple organ system failure. To evaluate whether this dysfunction increases with the length of sepsis, we studied the effect of fulminant CLP peritonitis with hyperoxia on mixed-function oxidase-MFO (cytochrome P450 content and activity) and lipid peroxidation in rat livers. Livers were harvested at 18, 21, 24, and 27 hr, homogenized, and microsomal fractions prepared. Cytochrome P450 concentration was determined by assay and P450 activity was determined by the metabolism of ethoxyresorufin and ethoxycoumarin. Lipid peroxidation was estimated by measuring malondialdehyde content. Septic rats showed decreases in P450 levels and activity, which worsened with duration of sepsis. These decreases were partially lessened by hyperoxia. Although there was a trend toward increased lipid peroxidation, this effect was not statistically significant. This study suggests that while MFO content and activity decrease with sepsis, these decreases do not appear to be related to the production of oxygen-derived free radicals. Furthermore, hyperoxia actually appears to have a protective role in this instance.
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PMID:Mixed-function oxidase activity in sepsis. 853 82

In this investigation, we tested the hypothesis that the cytochrome P-450 (CYP) inhibitor 1-aminobenzotriazole (ABT) alters the susceptibility of rats to hyperoxic lung injury. Male Sprague-Dawley rats were treated i.p. with ABT (66 mg/kg), i.v. with N-benzyl-1-aminobenzotriazole (1 micromol/kg), or the respective vehicles, followed by exposure to >95% oxygen for 24, 48, or 60 h. Pleural effusion volumes were measured as estimates of hyperoxic lung injury, and lung microsomal ethoxyresorufin O-deethylation (EROD) (CYP1A1) activities and CYP1A1 apoprotein levels were determined by Western blotting. ABT-pretreated animals exposed to hyperoxia died between 48 and 60 h, whereas no deaths were observed with up to 60 h of hyperoxia in vehicle-treated animals. In addition, three of four ABT-treated rats exposed to hyperoxia for 48 h showed marked pleural effusions. Exposure of vehicle-treated rats to hyperoxia led to 6.3-fold greater lung EROD activities and greater CYP1A1 apoprotein levels than in air-breathing controls after 48 h, but both declined to control levels by 60 h. Liver CYP1A1/1A2 enzymes displayed responses to hyperoxia and ABT similar to the effects on lung CYP1A1. N-Benzyl-1-aminobenzotriazole markedly inhibited lung microsomal pentoxyresorufin O-depentylation (principally CYP2B1) activities in air-breathing and hyperoxic animals but did not affect lung EROD or liver CYP activities. In conclusion, the results suggest that induction of CYP1A enzymes may serve as an adaptive response to hyperoxia, and that CYP2B1, the major pulmonary CYP isoform, does not contribute significantly to hyperoxic lung injury.
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PMID:Potentiation of oxygen-induced lung injury in rats by the mechanism-based cytochrome P-450 inhibitor, 1-aminobenzotriazole. 1064 Feb 92

This article describes a metabolite profiling method for evaluating the effect of oxygen exposure on human liver microsomal metabolism of mitomycin C (MC) in the presence of glutathione (GSH) and NADPH under hypoxic (100% helium), limitedly and fully aerobic, and hyperoxic (100% oxygen) conditions. MC and its metabolite(s) were characterized and the relative percentages of these components were estimated at different incubation times using liquid chromatography and quadrupole time-of-flight mass spectrometry. The MC metabolite profiles were confirmed using purified human cytochrome P450 reductase, acidic activation, and UV-Vis detection at 550 nm. In hypoxia, MC was exclusively metabolized into 2,7-diaminomitosene-10-glutathione-S-conjugate (2,7-DAM-10-SG) within 30 min, whereas approximately 5% of this conjugate, 16% of 2,7-diaminomitosene (2,7-DAM), and 77% of MC were observed under a fully aerobic condition at 90 min. Under limitedly aerobic conditions, the relative percentages of the two metabolites in incubations varied greatly depending on the volume ratio of air to liquid. In hyperoxia, 2% of 2,7-DAM-10-SG, 9% of 2,7-DAM, and 86% of MC were obtained at 90 min. The results indicate that oxygen strongly inhibits the in vitro metabolism of MC. These data suggest that GSH may serve a dual function in facilitating the formation of a leucoaziridinomitosene followed by electron rearrangement giving intermediate metabolite 2,7-DAM, and then trapping this intermediate giving rise to 2,7-DAM-10-SG. These findings provide direct evidence for understanding the fate of oxygen-sensitive metabolic deactivation of MC by GSH.
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PMID:Evaluation of the effect of oxygen exposure on human liver microsomal metabolism of mitomycin C in the presence of glutathione using liquid chromatography-quadrupole time of flight mass spectrometry. 1600 24

Sex-specific differences in pulmonary morbidity in adults and preterm infants are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. Cytochrome P450 (CYP) 1A enzymes have been shown to play a mechanistic role in hyperoxic lung injury (HLI) in animal models. Whether CYP1A enzymes contribute to gender-specific differences in relation to HLI is unknown. In this investigation, we tested the hypothesis that mice will display gender-specific differences in HLI, and that this phenomenon will be altered in mice lacking the genes for Cyp1a1 or 1a2. Eight week-old male and female wild type (WT) (C57BL/6J) mice, Cyp1a1-/-, and Cyp1a2-/- mice were exposed to 72h of hyperoxia (FiO2>0.95). Lung injury and inflammation were assessed and pulmonary and hepatic CYP1A1 and CYP1A2 levels were quantified at the enzyme activity, protein and mRNA level. Upon exposure to hyperoxia, liver and lung microsomal proteins showed higher pulmonary CYP1A1 (apoprotein level and activity) in WT females compared to WT males and a greater induction in hepatic CYP1A2 mRNA levels and activity in WT females after hyperoxia exposure. The gender based female advantage was lost or reversed in Cyp1a1-/- and Cyp1a2-/- mice. These findings suggest an important role for CYP1A enzymes in the gender-specific modulation of hyperoxic lung injury.
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PMID:Sex-specific differences in hyperoxic lung injury in mice: role of cytochrome P450 (CYP)1A. 2570 76


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