Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-1 has been shown to prolong the survival of rats exposed to lethal concentrations of oxygen. This oxygen tolerance has been attributed by some workers to an increase of manganese superoxide dismutase. We report here that the administration of interleukin-1 to male adult rats results in (i) significant decrease of pulmonary cytochrome P450 at 24 and 72 hours, (ii) decrease of P450 IIB1 mRNA at 24 and 72 hours and (iii) significant decrease of superoxide anion generation from pulmonary microsomes isolated from treated rats. To the best of our knowledge, this is the first report to demonstrate these effects of interleukin-1 on pulmonary P450 and its oxidase activity (O2- generation). On the basis of these results and several earlier reports in which various P450 depressants have been shown to depress superoxide production from microsomes and to prolong the lives of rodents in hyperoxia, we conclude that oxygen tolerance induced by interleukin-1 administration is likewise mediated, at least in part, by reduced generation of superoxide anion from cytochrome P450 monooxygenase system.
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PMID:Suppressive effect of interleukin-1 on pulmonary cytochrome P450 and superoxide anion production. 132 Aug 74

The effect of hyperoxia (O2 > 95%) for 48 hours on the induction of pulmonary and hepatic cytochrome P450 has been investigated in adult male rats. Northern blot analysis using six "specific" oligonucleotide probes indicated that CYP 1A1 and CYP 1A2 mRNAs in liver and CYP 1A1 mRNA in lung were significantly increased by hyperoxic exposure, whereas the major constitutive P450 mRNAs, CYP 2C11 in liver and CYP 2B1 in lung, were decreased. Since induction of CYP 1A1 has only been reported with the use of exogenously administered xenobiotics, further studies were carried out to confirm the results obtained with Northern blot analysis. cDNAs were synthesized for CYP 1A1 and 1A2 in the liver and CYP 1A1 in the lungs and amplified by reverse PCR. These results indicate that these cDNAs were amplified significantly more in the hyperoxia group than in the control animals. Futhermore, CYP 1A1 and 1A2 proteins in liver and CYP 1A1 protein in lungs as well as the corresponding monooxygenase activities were increased by hyperoxia. Hyperoxic induction of CYP 1A1 and 1A2 is the first demonstration of nonexogenous CYP 1A induction in animals and indicates the needs to pursue the changes of Ah receptor-ligand-DNA interaction in hyperoxia.
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PMID:Induction of cytochrome P450 1A1 and 1A2 by hyperoxia. 826 28

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

Although reductions in retinal blood flow (RBF) in response to acute hyperoxia are well described, the mechanistic basis of this response has yet to be clarified. The present study was undertaken in order to determine the possible involvement of two arachidonic acid-derived vasoconstrictors, the cyclooxygenase metabolite thromboxane and the cytochrome P450 metabolite 20-HETE, as well as the involvement of the peptide endothelin and superoxide free radical. Fluorescein videoangiography was performed on the intact eyes of isoflurane-anesthetized newborn piglets. RBF responses to 20 min of hyperoxia were calculated from the angiograms off-line, using changes in mean arteriovenous transit times and arteriolar and venular diameters. The effect of hyperoxia (PaO2=351+/-9 mmHg; n=39) on RBF was examined in each animal under control conditions and again after intravitreal perivascular administration of drugs that block the synthesis or receptors of known vasoconstrictors. Estimated RBF decreased by a maximum of 42+/-3% in the 7 animal groups in response to 20 min of hyperoxia. The magnitude and time course of the change in RBF resulting from two successive hyperoxic challenges did not differ, and were unaffected by intravitreal administration of vehicle. The response to hyperoxia was attenuated 46+/-6 (n=6; P=0.001) after intravitreal CGS 22652 (2 nmol), a combined thromboxane synthesis inhibitor and receptor antagonist. DDMS (12.5 nmol), a competitive inhibitor of the P450 enzyme omega-hydroxylase that forms 20-HETE, blocked hyperoxic constriction by 23+/-7% (n=6; P=0.01). Intravitreal pretreatment with TBC 1241z (2 nmol), a receptor antagonist of the peptide endothelin, blocked the hyperoxic response by 26+/-5% (n=6; P=0.01). A combination of CGS 22652 (2 nmol), DDMS (12.5 nmol), and TBC 1241z (2 nmol), blocked the hyperoxic flow response by 51+/-3% (n=5; P=0.003). Administration of a combination of superoxide dismutase (10 U intravitreally, 10000 U kg-1 of the polyethylene glycol-conjugate intravenously) and catalase (10 U intravitreally, 10000 U kg-1 intravenously) was without effect on hyperoxia-induced reductions in RBF (n=5). The present results indicate that the arachidonic acid metabolites thromboxane and 20-HETE, and the peptide endothelin, participate in mediating the acute reduction in RBF in response to hyperoxia.
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PMID:Mechanisms of hyperoxia-induced reductions in retinal blood flow in newborn pig. 977 17

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

Cytochrome P450 monooxygenases (CYPs) represent large class of heme-containing enzymes that catalyze the metabolism of various endogenous and exogenous substrates. Although they are found in many tissues, the function of the particular subset of their isoforms does not appear to be the same. Many CYP genes exhibit sexually dimorphic expression, while others are sex-independent. Moreover, as a source of reactive oxygen species (ROS), P450 system is believed to play the important role in various pathological conditions and diseases. The aim of this study was to observe the effect of hyperoxia on oxidant/antioxidant status in the liver of young male and female mice and to determine whether the observed effects are associated with the expression of Heme oxygenase-1 (HO-1) and CYP genes associated with stress (Cyp1a1, Cyp1a2, Cyp2a5, and Cyp2e1) or stress and gender-related responses (Cyp2b9). In this study, we demonstrated gender-related effect of hyperoxia on oxidant/antioxidant status and on expression of certain P450 enzymes. Our results suggest that females are less susceptible to hyperoxia induced oxidative stress by two major mechanisms: upregulated expression of HO-1 genes and different expression of certain P450 enzymes. Therefore, our study could provide additional data of gender-dependent responses in susceptibility to oxidative stress, chemical toxicity and drug efficiency in treatment of diseases.
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PMID:Cytochrome P450 gender-related differences in response to hyperoxia in young CBA mice. 2022 64