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)

Age-related changes in pulmonary formation of arachidonic acid (AA) metabolites are thought to play an important role in regulating cardiopulmonary function. This study addresses the potential role of reduced glutathione (GSH) in modulating cyclooxygenase product formation in the developing lung. Prostaglandin H2 (PGH2) metabolism was studied in microsomal fractions isolated from the lungs of unventilated fetal, neonatal and adult goats. GSH-dependent PGH2 to PGE2 isomerase activity in microsomal fractions from the perinatal (fetal and neonatal) goat lung was not saturable with respect to GSH and can respond to changes in GSH concentration over the range of 0.01 to 30 mM, which encompasses the full range the intracellular GSH levels reported in the literature. However, in fractions from the adult, a lower rate of PGE2 formation is observed at higher GSH concentrations. In addition, the tissue levels of GSH exhibited developmental stage-related differences with fetal being higher than neonatal or adult. The present observations may have physiologic relevance, in that decreases in pulmonary GSH levels after birth may contribute to decreases in plasma PGE2 levels by decreasing pulmonary PGE2 synthesis, thereby contributing to closure of the ductus arteriosus; conversely, increased GSH levels associated with hyperoxia may contribute to persistence of ductal patency. Formation of 6-keto-PGF1 alpha and of TXB2 (the stable metabolites of prostacyclin and TXA2) was decreased when PGE2 formation was increased by GSH activation of PGE2 isomerase in fractions isolated from all three developmental stages. A similar pattern of product formation was observed when AA was employed as substrate. These data suggest the possibility that changes in GSH concentration may modulate eicosanoid formation in cells that contain GSH-dependent PGE2 isomerase, as well as either or both prostacyclin or thromboxane synthase(s).
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PMID:Concentration-activity profile of the modulation of cyclooxygenase product formation by reduced glutathione in microsomal fractions from the goat lung. 211 78

We have previously reported that bronchoalveolar lavage fluid cyclo-oxygenase products of arachidonic acid (AA) metabolism increase prior to the development of significant hyperoxic lung injury. To further assess the role of AA metabolites in the development of hyperoxic lung injury, we have utilized this same model of hyperoxic lung injury and administered either indomethacin (an inhibitor of the cyclo-oxygenase pathway of AA metabolism) or dexamethasone (inhibitor of AA release). A total of 46 adult rabbits were exposed to greater than 95% oxygen for 65 hours. Fourteen animals were given either 2 or 3 mg/kg/day indomethacin, 7 served as controls: 18 animals were given either 0.5 or 1.0 mg/kg/day of dexamethasone, 7 served as controls. The surviving animals were sacrificed after 65 hours of hyperoxia and bronchoalveolar lavage of the left lung was done; the right lung was examined by light microscopy. Treatment with indomethacin or dexamethasone failed to ameliorate the hyperoxic lung injury process. However, in both the indomethacin and dexamethasone treatment groups, significant suppression of 6-keto-PGF1 alpha, a PGI2 metabolite, was observed. Some suppression of TXB2 production was observed, but there was no evidence of any decrease in leukotriene production. We postulate that failure to ameliorate hyperoxic lung injury with either indomethacin or dexamethasone therapy was related to significant suppression of PGI2, a potentially protective AA metabolite, and/or to failure to significantly decrease production of potential pathogenic participants, such as TXA2 or LTB4.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Failure of non-selective inhibition of arachidonic acid metabolism to ameliorate hyperoxic lung injury. 313 85