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

Metabolites of arachidonic acid (AA) released into bronchoalveolar lavage fluid of animals exposed to hyperoxia have previously been implicated as mediators of pulmonary oxygen toxicity. The alveolar macrophage (AM) represents an important potential source of these eicosanoids. We have therefore investigated the effects of in vitro hyperoxia (95% O2/5% CO2) versus normoxia (95% air/5% CO2) on the metabolism of AA in the AM of the rat. Exposure to 95% O2 for up to 72 h did not impair the viability or affect the protein content of cultured AMs. Hyperoxia for 24 to 72 h increased the accumulation of free AA liberated from endogenous stores in cultures of resting AMs. Despite this increase in free AA, no changes in synthesis of thromboxane B2, prostaglandin (PG) E2, PGF2 alpha, leukotriene (LT) B4, or LTC4 were observed in resting AMs exposed to hyperoxia for up to 72 h. This was not due to degradation of eicosanoids in hyperoxia. However, formation of cyclooxygenase metabolites from exogenously supplied AA was reduced in hyperoxia-incubated AMs, suggesting that hyperoxia inhibited the cyclooxygenase enzyme. In AMs stimulated with calcium ionophore A23187, both AA release and synthesis of cyclooxygenase and lipoxygenase eicosanoids were augmented after incubation in hyperoxia for 24 to 72 h. The increase in A23187-stimulated LTB4 synthesis caused by hyperoxia was inhibited by the antioxidants catalase, superoxide dismutase, and the intracellular cysteine loading agent L-2-oxothiazolidine-4-carboxylic acid, suggesting that the augmentation by hyperoxia of A23187-induced AA metabolism was mediated by reactive oxygen metabolites. Thus, hyperoxia has complex effects on AA metabolism in the AM, which include the ability to augment the release of AA and formation of bioactive eicosanoids. These findings support a possible role for eicosanoid synthesis by the AM in the pathogenesis of oxygen toxicity of the lung.
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PMID:Complex effects of in vitro hyperoxia on alveolar macrophage arachidonic acid metabolism. 215 14

Effects of ibuprofen (I), a cyclooxygenase inhibitor, and of nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, on bleomycin (B) and hyperoxia (H) induced acute lung damage and mortality were studied in hamsters. Hamsters, after receiving bleomycin, 0.25 unit, intratracheally were treated subcutaneously with vehicle (BHV group), ibuprofen, 10 mg/kg, (BHI group) or NDGA 10 mg/kg (BHNDGA group) and then exposed to 70% oxygen (O2) for 72 h. Daily treatment in each case continued for 14 days. The cumulative mortality at 0, 2, 4, 7, and 14 days after O2 exposure was as follows: 0, 5, 13, 26, and 50%, in BHV; 0, 10, 21, 33, and 67% in BHI; and 2, 21, 51, 71, and 92% in BHNDGA groups, respectively. The lung hydroxyproline content in pooled control hamsters averaged 721.1 +/- 22.3 (SE) micrograms/lung. The lung hydroxyproline content in animals in BHV, BHI, and BHNDGA groups was significantly increased at 4, 7, and 14 days after exposure when compared to controls. There were, however, no significant differences in the hydroxyproline content of the lungs among animals in BHV, BHI, and BHNDGA groups at any post-exposure time. Morphology of lungs of the BHV group showed an infiltrate of monocytes, lymphocytes, and some neutrophils (PMN) at 2 days but was composed primarily of monocytes and macrophages at 4, 7, and 14 days post-exposure. Multifocal fibrosis was observed at 7 days and was more diffuse by 14 days. Multifocal fibrosis in lungs from the BHI group was seen at 4 days with foci being larger at 7 and 14 days. Multifocal epithelial necrosis was observed at 14 days.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increases in severity of lung damage and mortality by treatment with cyclo and lipoxygenase inhibitors in bleomycin and hyperoxia model of lung injury in hamsters. 245 5

Deleterious pulmonary effects of hyperoxia are thought, in part, to be mediated by high-energy radicals and inflammatory reactions. It has been suggested that arachidonate metabolites, such as leukotrienes, may be responsible for the latter mechanism. We sought to demonstrate that concurrent exposure to hyperoxia and indomethacin, a potent inhibitor of cyclooxygenase, would increase pulmonary inflammation. A total of 50 female guinea pigs were treated as pairs with 95.6% oxygen or air and separately with 0.3 mg/kg of indomethacin or normal saline every 12 h for 3 days. A significant increase in leukocytes in bronchopulmonary lavage subsequent to combined oxygen and indomethacin treatment was observed when compared with either oxygen, indomethacin, or air treatments alone (p less than 0.05). Although oxygen treatment did alter pulmonary volume-pressure relations (p less than 0.05), hyperoxia alone or with concurrent indomethacin treatment did not alter elastance or histologic structures. These findings suggest that pulmonary inflammation in response to hyperoxia may be augmented by indomethacin. We speculate that increased lipoxygenase products of arachidonate metabolism may be partially responsible for these changes.
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PMID:Pulmonary oxygen toxicity in the guinea pig. Effect of indomethacin. 271 57

This study investigated the response of bovine pulmonary artery endothelial cells to incubation in hyperoxia (95% O2-5% CO2). Changes in cell number and morphology, release of lactate dehydrogenase, and production of arachidonic acid metabolites were assessed during continuous exposure of confluent endothelial monolayers to air (air-5% CO2, "controls") or O2 (95% O2-5% CO2, "O2-exposed") for periods of 12-72 h. Control monolayer cell numbers remained constant (approximately 2,000,000 cells/flask), whereas the number of cells in O2-exposed monolayers decreased progressively to 30% of controls (P less than 0.01) by 72 h. As assessed by radioimmunoassay, both control and O2-exposed cells produced the prostacyclin metabolite, 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), and prostaglandin F2 alpha (PGF2 alpha), but no thromboxane metabolite (TxB2) was detected. The O2-exposed cells released significantly more 6-keto-PGF1 alpha and PGF2 alpha than control cells when apparent net production rates over the entire 72-h period were compared. In addition, both control and O2-exposed (48 h) endothelial monolayers released immunoreactive leukotriene B4 (LTB4) on stimulation with calcium ionophore (10 microM A23187). As with the cyclooxygenase products, O2-exposed cells released more immunoreactive LTB4 than did controls. Both cyclooxygenase and lipoxygenase metabolites of arachidonic acid are released by cultured endothelial cells during the development of O2 toxicity.
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PMID:Production of arachidonic acid metabolites by endothelial cells in hyperoxia. 301 13

To further study the role of arachidonic acid metabolites in the development of hyperoxic lung injury and the function of PMNs and/or alveolar macrophages in facilitating this role, we exposed adult rabbits to greater than 95% O2 or air for 24, 40, 48, or 65 hours. At the end of each study, bronchoalveolar lavage [BAL] of the left lung was performed, and the right lung was inflated and fixed for light and electron microscopy. PGE2, 6-keto-PGF1 alpha and thromboxane B2 were measured by RIA in arterial and venous plasma at the beginning and end of each study and in BAL fluid obtained at sacrifice. Production of these three PGs by BAL cells placed in cell culture was also measured. Significant hyperoxic lung injury did not develop until 65 hours, as evidenced by significant increase in BAL total protein and percent PMNs, and by morphologic findings. At 40 hours, however, BAL fluid PGE2 and 6-keto-PGF1 alpha increased and BAL cell production of all 3 PGs was significantly increased (p less than .05). In summary, the early PG increases observed in these studies may directly contribute to the development of hyperoxic lung injury or, rather, may be representative of a generalized increase in all arachidonic acid metabolites, including the lipoxygenase pathway. The increase in BAL cell PG production and increased PG concentrations in BAL fluid prior to any increase in BAL PMNs suggest that the AM may be the source of the early arachidonic acid metabolite increase in response to hyperoxia.
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PMID:The early involvement of pulmonary prostaglandins in hyperoxic lung injury. 310 36