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

Exposure of rainbow trout to environmental hyperoxia (PIO2 approximately 530 Torr) resulted in an extracellular respiratory acidosis which was fully compensated by 72 h; return to normoxia (PIO2 approximately 145 Torr) at this time induced a metabolic alkalosis which was corrected by 24 h. Intracellular pHi ([14C]DMO method), fluid volumes [3H]PEG-4000 method), and electrolytes were monitored. Environmental hypercapnia (PICO2 approximately 6.5 Torr) was employed to confirm that intracellular responses were specific to respiratory acidosis. Gill pHi did not change during respiratory acidosis despite a very low non-HCO3- buffer capacity, but gill ICFV decreased markedly. A large loss of gill intracellular [Cl-]i in excess of [Na+]i, combined with a substantial gain in [K+]i, contributed to gill pHi regulation by raising branchial [SID]i. In weakly buffered brain tissue, active adjustment of pHi started within 3 h, but two well buffered tissues, RBC and white muscle, exhibited compounding metabolic acidoses during the first 12-24 h. The muscle response was associated with small increases in ICFV and [Cl-]i, and a large decrease in [K+]i which reduced muscle [SID]i. We hypothesize that this initial export of K+ and basic equivalents served to regulate pH in more critical compartments (e.g. gills, brain) at the expense of muscle acidosis. By 48 h, pHi restoration in all tissues was complete, in advance of pHe regulation (72 h). Return to normoxia at 72 h elevated muscle, brain, and gill pHi, but there was no evidence of a comparable 'altruistic' role of muscle during this metabolic alkalosis. Regulation of pHi was complete by 24 h recovery, accompanied by partial or complete restoration of intracellular ions and fluid volumes.
 ...
PMID:Intracellular acid-base responses to environmental hyperoxia and normoxic recovery in rainbow trout. 175 56

Two major lines of defense exist against oxidant lung injury: tissue antioxidants and antioxidant enzymes. We studied pretreatment with the antioxidants, vitamin E and butylated hydroxyanisole (BHA), and the antioxidant enzymes, superoxide dismutase (SOD) and catalase, in rabbits exposed to 100% O2 for 48 h. BHA (200 mg/kg ip) or vitamin E (50-100 mg/kg po) were given for 2 or 3 days, respectively, before O2 exposure. Combined therapy with polyethylene glycol- (PEG) conjugated SOD (12 mg/kg) and catalase (200,000 U/kg) was given intraperitoneally 1 h before and 24 h after beginning 100% O2. Hyperoxia significantly increased the pulmonary content of malondialdehyde, indicating enhanced lipid peroxidation. One hundred percent O2 also increased lung weight gain and alveolar-capillary permeability to aerosolized 99mTc-labeled diethylenetriaminepentaacetate (99mTc-DTPA, 500 mol wt) and fluorescein isothiocyanate-labeled dextran (7,000 mol wt). Pretreatment with vitamin E, BHA, or the combination of PEG-SOD and PEG-catalase prevented the increase in malondialdehyde, lung weight gain, and alveolar-capillary permeability caused by hyperoxia. These results indicate that augmenting either tissue antioxidants or antioxidant enzymes can prevent the pulmonary injury caused by 48 h of 100% O2 in rabbits.
 ...
PMID:Antioxidants and antioxidant enzymes protect against pulmonary oxygen toxicity in the rabbit. 234 49

Deficiencies of antioxidants and increased free radical generation may explain the high incidence of bronchopulmonary dysplasia in premature infants. Long-acting antioxidants such as polyethylene glycol (PEG) conjugated superoxide dismutase (SOD), and catalase might modify this process. We delivered 32 premature lambs, 16 pairs of twins, by cesarean section at 125-141 days of gestation (term 146 days) and stabilized them on ventilators in normocapnic hyperoxia for a period of 8 h. One lamb of each twin pair received an intravenous dose of 7,500-50,000 IU/kg of PEG-SOD and of 37,500-1,000,000 IU/kg of PEG-catalase at birth. Their siblings acted as controls. Mean airway pressure, arterial pressure, and heart rate were recorded continuously. Arterial blood gases and pH were obtained every 30 min. After sacrifice, standardized lung biopsies were prepared for quantitative morphometrics and electron microscopy. Administration of PEG antioxidants at birth reduced the influx of neutrophils and macrophages into the lung and damage to arterioles, bronchiolar mucosa, and type II pneumocytes without major changes in alveolar surface area or pulmonary function. These effects were dose-related and detectable even at the lowest doses of PEG antioxidants administered.
 ...
PMID:Mitigation of pulmonary oxygen toxicity in premature lambs with intravenous antioxidants. 235 45

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.
 ...
PMID:Polyethylene glycol-attached antioxidant enzymes decrease pulmonary oxygen toxicity in rats. 254 Jan 39

Plasma membrane vesicles were prepared from porcine pulmonary artery endothelial cells by a dextran-polyethylene glycol two-phase system. Specific carrier-mediated transport of 5-hydroxytryptamine (5-HT) into the vesicles was examined. Transport required a Na+ gradient (out greater than in) across the membrane, and accumulated 5-HT rapidly effluxed out of the vesicles when the ionophore gramicidin was added. Transport was inhibited by the antidepressant imipramine. 5-HT transport into plasma membrane vesicles appeared saturable and exhibited Michaelis-Menten kinetics (Km 7.4 microM, maximal velocity 217 pmol.min-1.mg membrane protein-1). A 24-h exposure to 95% O2 at 1 atmosphere absolute resulted in a 21% decrease (P less than 0.05) in specific 5-HT transport by plasma membrane vesicles. Hyperoxia also caused a significant (P less than 0.01) decrease in plasma membrane fluidity, as measured with the fluorescence probe 1,6-diphenyl-1,3,5-hexatriene. These results indicate that pulmonary artery endothelial cell plasma membrane vesicles provide a good model for studying 5-HT transport activity in vitro. Hyperoxia affects plasma membrane fluidity and 5-HT transport in pulmonary artery endothelial cells, suggesting a possible cause-and-effect relationship between the two.
 ...
PMID:Serotonin transport and fluidity in plasma membrane vesicles: effect of hyperoxia. 337 69

The 27-day-old rat exposed to 100% oxygen (O2) for 8 days will have predictable lung vascular and parenchymal changes at 60 days of age. Using this model, the goals of this study are (1) to measure the lung antioxidant enzyme activities serially following intratracheal PEG antioxidant therapy during the 8-day O2 exposure; and (2) to assess chronic cardiopulmonary changes in the O2-exposed rats treated with PEG-CAT and/or PEG-CuZn SOD given intraperitoneally (IP) and/or intratracheally (IT). The study encompassed 202 male rats exposed to room air or oxygen. CuZn SOD doses were 300 U IT and 2000 U IP. The CAT dose was 500 or 4000 U IT and 10,000 U IP. At 60 days of age, the right ventricular systolic pressure (RVP), RV weight, % acinar wall arterial thickness, and parenchymal air space were significantly increased in O2-exposed rats compared to RA rats. The RVP, RV weight, and parenchymal changes were prevented by daily IT PEG-CAT 4000 U + CuZn SOD 300 U but the increased small artery muscularization was not. Three hours after the initial dose of IT PEG-CAT 4000 U, lung CAT activity was more than doubled and remained constant throughout the 8-day daily treatment course. This dose of CAT depressed the induction response to O2 of CuZn and MnSOD. It is concluded that daily intratracheal administration of PEG-CAT 4000 U + CuZn SOD 300 U can significantly ameliorate some of the chronic parenchymal and vascular lung O2 toxic changes. However, it appears that high-dose exogenous PEG-CAT suppresses the endogenous enzyme induction to hyperoxia of both CuZn and Mn-SOD.
 ...
PMID:Lung antioxidant enzymes and cardiopulmonary responses in young rats exposed to hyperoxia and treated intratracheally with PEG catalase and superoxide dismutase. 846 59

Hyperoxic lung injury may be mitigated by increasing alveolar epithelial antioxidant activity. We examined whether intratracheal instillation of superoxide dismutase (SOD) and catalase, conjugated to polyethylene glycol (PEG) to permit cellular access, reduces hyperoxic lung injury. Adult rats, pretreated intratracheally with 1,500 U PEG-SOD and 10,000 U PEG-catalase or with inactivated PEG-SOD/catalase, 1% PEG, or saline (treated controls), were exposed to hyperoxia (fraction of inspired oxygen > 0.95) for 48 h and compared with untreated air controls. Alveolar wash protein values in the treated control groups were significantly higher than in the PEG-SOD/catalase and air control groups, which had comparable values. Lung homogenate and alveolar type II cell SOD and catalase activities were higher after PEG-SOD/catalase treatment and lower after the control treatments when compared with untreated air controls. Lung homogenate dipalmitoyl phosphatidylcholine decreased and alveolar wash dipalmitoyl phosphatidylcholine increased after hyperoxia, but these changes were less after PEG-SOD/catalase treatment. Rats pretreated intratracheally with PEG-SOD/catalase survived significantly longer in hyperoxia than saline controls. These data indicate the potential of intratracheal antioxidant treatment to reduce pulmonary oxygen toxicity.
 ...
PMID:Mitigation of pulmonary oxygen toxicity in rats by intratracheal instillation of polyethylene glycol-conjugated antioxidant enzymes. 847 11

A newborn rat model of retinopathy of prematurity was used to test the hypothesis that a lack of superoxide dismutase contributes to the retinal vaso-attenuation seen during exposure of the animals to hyperoxic conditions. To determine the endogenous superoxide dismutase activity of the retina under hyperoxic conditions, litters of albino rats were placed in either constant 80% ambient oxygen (constant hyperoxia), or placed in 21% oxygen (room air) immediately after birth. Every other day, for 14 days, several rat pups were sacrificed and their retinas removed for the determination of total superoxide dismutase (SOD) activity and manganese-associated SOD activity. An attempt was made to increase retinal SOD activity by intraperitoneal administration of exogenous SOD encapsulated in polyethylene glycol-modified liposomes. Additional litters were exposed to the same oxygen treatments and supplemented twice daily with either liposome-encapsulated superoxide dismutase in saline or liposomes containing saline without SOD. Animals were sacrificed at various time points for the determination of total superoxide dismutase activity and computer-assisted analysis of vessel density and avascular area. Animals raised in an atmosphere of constant 80% oxygen had significantly reduced levels of retinal superoxide dismutase activity through 6 days of life when compared to their room air-raised littermates. At 6 days of age, daily supplementation with liposome-encapsulated SOD had significantly increased retinal superoxide dismutase activity and reduced oxygen-induced vaso-attenuation as evidenced by increased vessel density and decreased avascular area, when compared to littermates exposed to constant hyperoxia that received control liposomes. Superoxide dismutase had no adverse effects on any of the animals regardless of treatment. Tracing experiments demonstrated that liposomes entered the retina and were found in cells morphologically resembling microglia. Delivery of SOD to the retina via long-circulating liposomes proved beneficial, suggesting that restoration and/or supplementation of endogenous antioxidants in oxygen-damaged retinal tissue is a potentially valuable therapeutic strategy.
 ...
PMID:Therapeutic effect of liposomal superoxide dismutase in an animal model of retinopathy of prematurity. 913 39

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.
 ...
PMID:Mechanisms of hyperoxia-induced reductions in retinal blood flow in newborn pig. 977 17

Pulmonary oxidant stress plays an important pathogenetic role in disease conditions including acute lung injury/adult respiratory distress syndrome (ALI/ARDS), hyperoxia, ischemia-reperfusion, sepsis, radiation injury, lung transplantation, COPD, and inflammation. Reactive oxygen species (ROS), released from activated macrophages and leukocytes or formed in the pulmonary epithelial and endothelial cells, damage the lungs and initiate cascades of pro-inflammatory reactions propagating pulmonary and systemic stress. Diverse molecules including small organic compounds (e.g. gluthatione, tocopherol (vitamin E), flavonoids) serve as natural antioxidants that reduce oxidized cellular components, decompose ROS and detoxify toxic oxidation products. Antioxidant enzymes can either facilitate these antioxidant reactions (e.g. peroxidases using glutathione as a reducing agent) or directly decompose ROS (e.g. superoxide dismutases [SOD] and catalase). Many antioxidant agents are being tested for treatment of pulmonary oxidant stress. The administration of small antioxidants via the oral, intratracheal and vascular routes for the treatment of short- and long-term oxidant stress showed rather modest protective effects in animal and human studies. Intratracheal and intravascular administration of antioxidant enzymes are being currently tested for the treatment of acute oxidant stress. For example, intratracheal administration of recombinant human SOD is protective in premature infants exposed to hyperoxia. However, animal and human studies show that more effective delivery of drugs to cells experiencing oxidant stress is needed to improve protection. Diverse delivery systems for antioxidants including liposomes, chemical modifications (e.g. attachment of masking pegylated [PEG]-groups) and coupling to affinity carriers (e.g. antibodies against cellular adhesion molecules) are being employed and currently tested, mostly in animal and, to a limited extent, in humans, for the treatment of oxidant stress. Further studies are needed, however, in order to develop and establish effective applications of pulmonary antioxidant interventions useful in clinical practice. Although beyond the scope of this review, antioxidant gene therapies may eventually provide a strategy for the management of subacute and chronic pulmonary oxidant stress.
 ...
PMID:Antioxidant strategies in respiratory medicine. 1640 15


1 2 Next >>