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)

Dexamethasone accelerates the late gestational rise in rat lung catalase activity; neonatal hyperoxia elevates rat lung catalase activity. We studied the regulation of catalase gene expression in these instances. Catalase mRNA/mg DNA increased to gestation day 22 and then fell to the concentration in adult lungs. The rate of transcription of catalase mRNA was higher on gestation day 22 than gestation day 19, whereas the half-life of catalase mRNA (approximately 7 h) was the same on both days. Dexamethasone given 48 and 24 h before expected birth (gestation 22 days) increased catalase mRNA concentration at days 20 and 22 without a change in catalase mRNA stability. Early postnatal hyperoxia (greater than 95% O2, 72 h) elevated catalase mRNA/mg DNA and doubled its half-life without changing its rate of transcription. We conclude the normal late gestational elevation of catalase activity and the increase of activity during prenatal dexamethasone treatment are regulated at the level of gene transcription. By contrast, the elevation of catalase activity during neonatal hyperoxia is mediated posttranscriptionally by increased catalase mRNA stability.
 ...
PMID:Perinatal rat lung catalase gene expression: influence of corticosteroid and hyperoxia. 171 85

We have examined the effect of dexamethasone on the metabolism of pulmonary surfactant in normal and hyperoxia-treated rats. The relative abundance of the surfactant-specific apoprotein A (SP-A) mRNA in lung tissues and the contents of disaturated phosphatidylcholine (DSPC) and SP-A were measured in bronchoalveolar lavage fluids and in lung tissues in 4-wk-old rats exposed to room air or greater than 90% oxygen for 7 d with or without simultaneous treatment with dexamethasone (0.5 mg/kg body wt for 7 d). The relative abundance of the SP-A mRNA was marginally increased by hyperoxia (1.3-fold over controls). Dexamethasone increased the relative abundance of the SP-A mRNA to a level comparable to that with hyperoxia treatment (1.5-fold over controls). In lavage fluids, the contents of DSPC and SP-A were increased by 4- and 6-fold over controls by hyperoxia, respectively, but they were increased only by 2-fold by dexamethasone. In lung tissues, the contents of DSPC and SP-A were increased by 3- and 2-fold over controls by hyperoxia, respectively. These values in lung tissues in the air-exposed rats were not significantly increased by dexamethasone. In hyperoxia-treated rats, dexamethasone did not significantly affect the relative abundance of the SP-A mRNA level and the contents of DSPC and SP-A in lavage fluids and lung tissues. These results indicate that mechanisms other than increased synthesis of SP-A are involved in hyperoxia-induced SP-A accumulation and that dexamethasone does not affect the abnormal accumulation of pulmonary surfactant induced by hyperoxia.
 ...
PMID:Effect of dexamethasone on pulmonary surfactant metabolism in hyperoxia-treated rat lungs. 201 54

Monolayer cultures of fetal rat mixed lung cells respond to sublethal concentrations (50%) of oxygen by a reduced growth rate. Exposure to 95% O2 causes growth arrest and cell loss. In the presence of serum the addition of dexamethasone (5.5 nM), tri-iodothyronine (5.5 nM), or insulin (5 microU/ml) appeared to increase the cytotoxicity of 95% O2. Under growth-arrested conditions, in the absence of serum or elevated O2 concentrations, all three agents influence cellular antioxidant enzyme activities. Dexamethasone (0.055 nM) increased CuZn superoxide dismutase activity by 72% and glutathione peroxidase activity by 94%. Triiodothyronine (5.5 nM) increased CuZn superoxide dismutase activity 93%. Insulin (5 microU/ml) increased CuZn superoxide dismutase activity 90%, and catalase activity 58%. Dexamethasone, but not tri-iodothyronine or insulin, seems to have a protective effect against subsequent acute hyperoxia under serum-free conditions. Local non-hormonal factors may also influence lung cell responses to acute increases in oxygen concentrations, since cells acutely exposed to 50% or 95% O2 release a transferable factor(s) into their culture medium which increases antioxidant enzyme activities of non-hyperoxic lung cells.
 ...
PMID:Hormonal and local factors influence antioxidant enzyme activity of rat fetal lung cells in vitro. 352 18

Endotoxin (500 micrograms/kg)-treated rats are very tolerant to hyperoxia (greater than 95% O2, 1 ATA). We have now attempted to determine if dexamethasone given to rats 1 h before a usually lethal dose of endotoxin would diminish endotoxin's lethality without substantially abrogating its capacity to confer tolerance to hyperoxia. Endotoxin (20 mg/kg) given alone killed 70-80% of air- or O2-breathing rats within 24 h; dexamethasone (0.6 mg) given 1 h before endotoxin decreased mortality at 24 h to 10-15%. About 90% of the rats that were alive 24 h after receiving dexamethasone plus endotoxin (20 mg/kg) survived 72 h of hyperoxia. Dexamethasone plus endotoxin (10 mg/kg) provided as much protection against pulmonary edema resulting from 72 h of hyperoxia as did 500 micrograms/kg endotoxin alone. Tolerance to hyperoxia produced by dexamethasone plus high-dose endotoxin was accompanied by a rise in the activity in the lung of antioxidant enzymes. We conclude that dexamethasone protects rats against the lethal effects of high doses of endotoxin without interfering with endotoxin's capacity to engender tolerance to hyperoxia.
 ...
PMID:Dexamethasone protects against high-dose endotoxin without loss of tolerance to oxygen. 370 Mar 5

The low rate of survival in patients with the adult respiratory distress syndrome (ARDS) may in part reflect a failure to consider that the lung's response to applied therapies may not be constant throughout the course of illness. To test this notion, we used hyperoxia to produce progressive lung damage in rats and administered dexamethasone at different times during O2 exposures of various lengths. Dexamethasone improved survival and decreased lung damage if given when exposure to hyperoxia was to be soon terminated; pulmonary inflammation was marked at the time at which the administration of dexamethasone led to increased survival. Dexamethasone worsened lung damage and diminished survival when given early during exposure to hyperoxia; inflammation was minimal early in the course of exposure to hyperoxia. These findings point to the need for a more analytical approach to research on therapy of ARDS; agents that are harmful at one time may be beneficial at another time.
 ...
PMID:Oxygen toxicity in rats. Varied effect of dexamethasone treatment depending on duration of hyperoxia. 400 43

To determine whether prenatal corticosteroid therapy had adverse effects on the tolerance of the newborn lung to prolonged high O2 exposure, pregnant rats were given injections of dexamethasone (0.2 mg/kg) at 48 and 24 hours prior to parturition, and the newborn pups were placed in 96% to 98% O2 for the first seven days of life. Dexamethasone treatment resulted in significant decreases in body weight (-17%), lung weight (-30%), lung weight/body weight (-22%), and lung DNA (-18%) compared to untreated rat pups. Despite this growth inhibition, the dexamethasone-treated pups had improved survival in hyperoxia (36/48 = 75% vs 29/48 = 60% for untreated rats, P = .055). In addition, substantial "catch-up" lung growth had occurred by seven days and was complete in 28-day-old rats. Dexamethasone did not interfere with normal pulmonary antioxidant enzyme responses to hyperoxia. Thus, prenatal dexamethasone did not compromise the relative tolerance of the newborn to pulmonary O2 toxicity.
 ...
PMID:The effect of prenatal dexamethasone treatment on oxygen toxicity in the newborn rat. 718 11

Dexamethasone (10 mg/kg/day) or vehicle was administered in a randomized, controlled fashion to 3-day preterm guinea pigs exposed to either 21% oxygen or 95% oxygen for 72 hr and maintained in room air for a further 96 hr. Treatment with dexamethasone had no effect on survival of preterm pups maintained in either 21% or 95% O2. Dexamethasone treatment reduced the growth rate of pups, the effect occurring earlier (0-3 days) in 21% O2-treated pups than in 95% O2-treated pups (5-7 days). Exposure to 95% O2 reduced the survival rate of preterm animals (73% vs 100%, P < 0.05). Surviving pups developed acute lung injury, characterized by the accumulation of a protein-rich exudate in the alveoli and an infiltration of inflammatory cells, particularly neutrophils into the lung. Dexamethasone treatment attenuated the pulmonary inflammatory cell infiltration, in particular neutrophils, both during oxygen exposure (16.4 x 10(4) vs 9.4 x 10(4)/mL; P < 0.05) and following return to ambient conditions (28.0 x 10(4) vs 5.1 x 10(4)/mL; P < 0.05). Elastase activity in bronchoalveolar lavage fluid, which was primarily of neutrophil origin, was unchanged by dexamethasone treatment. Dexamethasone-treated pups had increased pulmonary antioxidant enzyme activities (Cu/Zn-superoxide dismutase; Mn-superoxide dismutase, catalase and glutathione peroxidase) during recovery from oxidative injury. Although there was both a marked reduction in numbers of neutrophils in the lung and elevated pulmonary antioxidant enzyme activities in dexamethasone-treated pups, the degree of microvascular permeability, as determined by both the lung wet weight/dry weight ratio and the presence of plasma proteins in the lavage fluid, was unchanged. Combined, these results imply that dexamethasone, although capable of blunting the influx of neutrophils to the hyperoxia-exposed lung and inducing antioxidant defences in the immature lung, cannot modify the progression of acute oxygen-induced injury of the immature lung.
 ...
PMID:Dexamethasone treatment fails to reduce oxygen-induced lung injury in the preterm guinea pig. Effects on pulmonary inflammation and antioxidant status. 824 Apr 12

Although prenatal steroid therapy is known to enhance in utero maturation of the surfactant and antioxidant enzyme systems, little is known about the effects of steroids on the antioxidant system after birth. We measured activities of the antioxidant enzymes, catalase, superoxide dismutase, and glutathione peroxidase, in lung homogenates from both preterm and term rat pups after prenatal dexamethasone treatment. Enzyme activities were measured at birth and after exposure to > 98% oxygen. Dexamethasone treatment resulted in significantly higher survival of the preterm pups at 24 h (91.3% for dexamethasone versus 57% for saline). In preterm pups, the activities of catalase and superoxide dismutase at birth were higher after dexamethasone treatment (p < 0.05). However, after 24 h of hyperoxic exposure, there were no differences in activities of any of the antioxidant enzymes between the dexamethasone and control groups of prematurely born pups. In term pups, antioxidant enzyme activities did not differ significantly at birth; nor did they differ after 24 to 72 h of hyperoxic exposure in the dexamethasone and control treatment groups. Our results indicate that although prenatal dexamethasone treatment augments survival and catalase and superoxide dismutase activities at birth in preterm rat pups, dexamethasone does not result in altered early postnatal antioxidant enzyme activities after exposure to hyperoxia.
 ...
PMID:Antioxidant enzyme responses to hyperoxia in preterm and term rats after prenatal dexamethasone administration. 843 92

Pulmonary oxygen toxicity occurs after prolonged administration of increased fractions of inspired oxygen. Lung damage in this setting manifests as diffuse alveolar damage. In animals exposed to hyperoxia, increased numbers of alveolar macrophages are noted 72 h after initiation of high concentrations of oxygen. Monocyte chemotactic protein-1 (MCP-1) is a cytokine released by a number of cell types that has potent chemotactic activity for monocytes, precursor cells for alveolar macrophages. In the current study, we examined whether MCP-1 production was increased in response to hyperoxia. We used the monocyte/ histiocytic U937 cell line and exposed these cells to hyperoxia for variable amounts of time, then determined MCP-1 concentrations by enzyme-linked immunosorbent assay and MCP-1 mRNA levels by Northern blot analysis. We also examined the effects of dexamethasone on the response of U937 cells to hyperoxia. Finally, as a potential mechanism for regulation of U937 MCP-1 production, we examined effects of hyperoxia on MCP-1 mRNA stability. The results demonstrate that hyperoxia stimulates MCP-1 production after 6 and 24 h of exposure. MCP-1 mRNA levels are also increased after initiation of hyperoxia in part through effects on MCP-1 transcript stability. Dexamethasone significantly reduces MCP-1 production and mRNA levels also in part through effects on transcript stability. These studies suggest monocytes may be attracted to hyperoxia-exposed lungs through enhanced MCP-1 production. MCP-1 production appears to be upregulated in part through post-transcriptional processes in this setting.
 ...
PMID:Modulation of monocyte chemotactic protein-1 production by hyperoxia: importance of RNA stability in control of cytokine production. 953 39

We studied the regulation of GSH and the enzymes involved in GSH regulation, gamma-glutamylcysteine synthetase (gamma-GCS) and gamma-glutamyl transpeptidase (gamma-GT), in response to the oxidants menadione, xanthine/xanthine oxidase, hyperoxia, and cigarette smoke condensate in human alveolar epithelial cells (A549). Menadione (100 microM), xanthine/xanthine oxidase (50 microM/10 mU), and cigarette smoke condensate (10%) exposure produced increased GSH levels (240 +/- 6, 202 +/- 12, and 191 +/- 2 nmol/mg protein, respectively; P < 0.001) compared with the control level (132 +/- 8 nmol/mg protein), which were associated with a significant increase in gamma-GCS activity (0.18 +/- 0.006, 0.16 +/- 0.01, and 0.17 +/- 0. 008 U/mg protein, respectively; P < 0.01) compared with the control level (0.08 +/- 0.001 U/mg protein) at 24 h. Exposure to hyperoxia (95% O2) resulted in a time-dependent increase in GSH levels. gamma-GCS activity increased significantly at 4 h (P < 0.001), returning to control values after 12 h of exposure. Dexamethasone (3 microM) exposure produced a significant time-dependent decrease in the levels of GSH and gamma-GCS activity at 24-96 h. The activity of gamma-GT did not change after oxidant treatment; however, it was decreased significantly by dexamethasone at 24-96 h. Thus oxidants and dexamethasone modulate GSH levels and activities of gamma-GT and gamma-GCS by different mechanisms. We suggest that the increase in gamma-GCS activity but not in gamma-GT activity may be required for the increase in intracellular GSH under oxidative stress in alveolar epithelial cells.
 ...
PMID:Differential regulation of glutathione by oxidants and dexamethasone in alveolar epithelial cells. 968 38


1 2 Next >>