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)

Cyclosporin A (CsA), an inhibitor of protein phosphatase 2B (calcineurin), has been shown to play a role in exocytosis and neutrophil mobility. Hyperoxia (>95% oxygen for 72 h) causes lung injury and reduces lung compliance. This model is indicative of deficiencies in surfactant and elicits a vigorous immune response leading to further damage. We examined the effects of CsA on surfactant-secreting lung alveolar type II cells. CsA enhances ATP-stimulated increases in whole cell capacitance in the presence of 2 mM extracellular Ca2+. This measurement corresponds with increases in exocytosis. Because of its effect on the immune system and exocytosis from type II cells, CsA was examined for its protective effects against hyperoxia-induced lung damage in mice. We found that CsA (50 mg. kg-1. day-1) attenuated hyperoxia-induced reductions in lung compliance when administered before or during 72 h of >95% oxygen (P < 0.05). CsA (10 mg. kg-1. day-1) also had a protective effect against hyperoxia-induced changes in neutrophil infiltration, capillary congestion, edema, and hyaline membrane formation. Wet lung weight-to-dry lung weight ratios did not show any significant changes after hyperoxia or hyperoxia plus CsA (P < 0. 05). CsA may be useful to treat patients undergoing prolonged high-oxygen therapy and possibly other lung injuries.
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PMID:Cyclosporin A protects lung function from hyperoxic damage. 1033 35

Hyperoxia is known to induce extensive alveolar cell death by still poorly defined mechanisms. In this study, the mitochondria-dependent cell death pathway was explored during hyperoxia-induced lung injury in mice. We observed a progressive release of cytochrome c from the mitochondria into the cytosol of alveolar cells. This release was accompanied by the translocation of the proapoptotic protein Bax from cytosol to mitochondria without detectable activation of caspase-3. As cytochrome c release can be induced by mitochondrial membrane alteration and permeability transition (MPT), mice were treated with cyclosporin A, which specifically inhibits MPT. Cyclosporin A treatment prevented mitochondrial release of cytochrome c during hyperoxia and concomitantly preserved mitochondria from extensive swelling and crista disorganization, as assessed by electron microscopy analysis of alveolar epithelial cells. These morphological and biochemical observations correlated with decreased lung tissue damage, as evaluated by morphological score and lung weight. In conclusion, mitochondrial damage and cytochrome c release are important linked events in hyperoxia-induced lung injury and can be efficiently blocked by cyclosporin A.
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PMID:Mitochondrial cytochrome c release is a key event in hyperoxia-induced lung injury: protection by cyclosporin A. 1452 30

Cyclosporine effects on hyperoxia-induced histopathological and functional changes in the rat adult lung are controversial and the newborn lung has not been studied. Thus, we evaluated the effects of cyclosporine in young rats after 60% hyperoxia exposure postnatally. Experimental categories included: (1) room air for the first 5 postnatal weeks with daily subcutaneous injections of saline from postnatal day (PN)15 to PN35; (2) room air with daily injections of cyclosporine from PN15 to PN35; (3) 60% oxygen from PN0 to PN14 and then daily saline injections during the following three weeks; (4) 60% oxygen from PN0 to PN14 followed by cyclosporine treatment from PN15 to PN35. Hyperoxia significantly reduced the number of secondary crests and microvessel density, and it increased the mean alveolar size and septa thickness. Cyclosporine treatment did not significantly modify the hyperoxia-induced changes. Conversely, in normoxia, cyclosporine reduced microvessel density and the number of secondary crests. In conclusion, cyclosporine did not modify alveolar and microvascular parameters in hyperoxia exposure, although it caused some changes in normoxia.
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PMID:Cyclosporine and hyperoxia-induced lung damage in neonatal rats. 2345 24