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)

The pathogenesis of oxygen toxicity remains unknown but may involve leukocyte mediated injury. The effects of hyperoxia on several lower respiratory tract parameters were examined in bronchoalveolar lavage fluid of normal nonsmoking subjects who inhaled a fractional inspired oxygen concentration of 50 percent (mean exposure: 44 h). Evidence that 50 percent O2 produced oxidative stress in the lung included recovery of fluorescent products of lipid peroxidation and partial oxidation of alpha 1-antitrypsin in BAL fluid obtained after O2 exposure. To examine whether alveolar macrophage-derived leukotriene B4 may be generated in response to 50 percent O2, AM were isolated from O2-exposed subjects and compared with AM recovered from subjects breathing room air. Leukotriene B4 levels were elevated in supernatants from both unstimulated and arachidonic acid-stimulated AM obtained from hyperoxia-exposed subjects. In hyperoxia-exposed individuals, LTB4 levels were also elevated in extracted BAL fluid. The percentage of BAL neutrophils was also significantly increased after O2 exposure (2.8 +/- 0.6 vs 1.2 +/- 0.4 percent, p = 0.05). We conclude that an FIO2 of 50 percent inhaled for 44 h is associated with enhanced oxidative stress, stimulation of AM to release LTB4, and a small but significantly increased percentage of neutrophils recovered in BAL fluid.
 ...
PMID:Hyperoxic exposure in humans. Effects of 50 percent oxygen on alveolar macrophage leukotriene B4 synthesis. 131 Apr 57

Endotoxin protects against pulmonary oxygen toxicity in rats, and both prostaglandins and polymorphonuclear leukocytes (PMN) are implicated as playing an important role in this protective action. In this study, a bronchoalveolar lavage (BAL) technique was used to analyze cellular and eicosanoid composition of the lavage fluid of endotoxin-protected oxygen-exposed rats. The BAL fluid of the endotoxin-protected oxygen-exposed rats contained the highest number of PMN, while the BAL fluid of the nonprotected oxygen-exposed rats contained the highest number of macrophages. Thus, morbidity due to pulmonary oxygen toxicity was correlated with the number of macrophages but not with the number of PMN present in the BAL fluid. Leukotriene B4, thromboxane B2, and prostaglandin E2 levels were significantly higher in the lavage fluid of nonprotected oxygen-exposed rats compared to the levels in the lavage fluid of air-exposed rats. Eicosanoid levels in the BAL fluid of endotoxin-protected oxygen-exposed rats did not differ significantly from the levels found in air-exposed control rats. These findings suggest that endotoxin protects against hyperoxia-induced changes in eicosanoid metabolism.
 ...
PMID:Cellular and eicosanoid composition of bronchoalveolar lavage fluid in endotoxin protection against pulmonary oxygen toxicity. 253 7

Leukotriene B4 (LTB4) is a metabolite of arachidonic acid that has potent chemotactic activity for polymorphonuclear leukocytes (PMN). Pulmonary oxygen toxicity is considered to be a good model of an acute inflammatory lung injury, and an increase in the number of PMN is found in the lungs acutely injured by hyperoxia. In order to estimate the role of LTB4 responsible for this influx of PMN, we measured the LTB4 by radioimmunoassay in lung lavages of rats exposed to hyperoxia for 60 h. We found that the level of LTB4 in lung lavages in rats exposed to hyperoxia for 60 h increased significantly compared with that in normoxic control rats. At the same time, the marked increase in the number of PMN in lung lavages and the decrease in the activity of NADPH-cytochrome c reductase in lung microsomes were also observed. The administration of AA861, a 5-lipoxygenase inhibitor, reduced not only the increase in LTB4 but also the increase in the number of PMN in lung lavages of rats exposed to hyperoxia for 60 h. Furthermore, treatment with AA861 also protected the decrease in the activity of NADPH-cytochrome c reductase. The effects of AA861 on these parameters were observed in a dose-dependent fashion. In addition, there is a good correlation between the level of LTB4 and the number of PMN in the lavage of rats exposed to hyperoxia for 60 h with or without AA861 administration.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The role of leukotriene B4 in the genesis of oxygen toxicity in the lung. 301 Jul 81

Leukotriene B4 (LTB4) has been reported to promote the formation of lung oedema when infused into the pulmonary circulation of adult animals. The present study evaluated the hypothesis that LTB4 was responsible, in part, for the oedema that develops during oxidative injury of the immature lung. Significant increases were found in LTB4 concentration in bronchoalveolar lavage fluid obtained from pre-term guinea pig pups maintained in 95% oxygen for 48 h (P < 0.05) and 72 h (P < 0.05) compared to pups maintained in 21% oxygen. Cellular analysis of lavage fluid revealed a concurrent influx of neutrophils into the hyperoxic-injured lung at these times. The protein concentration of lavage fluid was also increased by 48-h hyperoxia exposure indicating elevated pulmonary microvascular permeability. In a second series of experiments, pups exposed to 95% oxygen (and 21% oxygen controls) were treated with a specific LTB4 antagonist (U-75302), at either 0.5, 1.5 or 3.0 mg 100 g body wt to ascertain if LTB4 played a role in either neutrophil recruitment or oedema formation in the immature lung. The number of neutrophils recovered in bronchoalveolar lavage fluid was significantly reduced, compared to vehicle-treated pups, in pups treated with U-75302, at both 1.5 and 3.0 mg/100 g body wt but not 0.5 mg/100 g body wt. Histopathological analysis of pups treated with 1.5 mg U-75302/100 g body wt revealed fewer neutrophils in the pulmonary interstitium (198 vs. 218 mm-2, P < 0.05). The extent of lung microvascular permeability, elevated by hyperoxic exposure, was modulated by increasing concentrations of U-75302. Specifically, treatment with 0.5, 1.5 and 3.0 mg U-75302/100 g body wt reduced microvascular permeability by 17, 67 and 98%, respectively. In conclusion, LTB4 plays an important role in oedema formation in acute oxidative injury of the immature lung and this is mediated, in part, through neutrophils.
 ...
PMID:Oxygen-induced lung injury in the pre-term guinea pig: the role of leukotriene B4. 749 13