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

Exposure of animals to oxidant gases produces a mild emphysema, and O2-derived free radicals are capable of degrading connective tissues in vitro. It is postulated that degradation of connective tissue by O2-derived free radicals leads to emphysema in these models. To determine whether exposure of lung tissue slices to an oxidant gas results in degradation of collagen and to investigate factors mediating this degradation, we exposed lung tissue slices from normal rats to hyperoxia (95% O2, 5% CO2) and measured hydroxyproline release into the medium. After a 4-h exposure, the hydroxyproline released was 5.3 +/- 0.2 micrograms/g lung tissue (n = 10) in normoxia and 8.1 +/- 0.6 micrograms/g tissue (n = 13) in hyperoxia (p less than 0.05), suggesting degradation of collagen. The addition of 0.1% trypsin to the initial incubation medium caused a synergistic increase in hydroxyproline release from O2-exposed slices: normoxia/trypsin, 46.2 +/- 3.6 micrograms/g tissue (n = 10); hyperoxia/trypsin, 61.4 +/- 3.6 micrograms/g tissue (n = 11) (p less than 0.05). The addition of proteinase inhibitors completely suppressed the O2-induced release of hydroxyproline, suggesting that proteolytic enzymes are involved in hyperoxia-mediated degradation of lung collagen.
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PMID:Degradation of collagen in lung tissue slices exposed to hyperoxia. 303 77

We previously demonstrated that hyperoxia-exposed immature rats develop airway smooth muscle layer thickening; this remodeling appears partially attributable to smooth muscle hyperplasia. In this study, we tested the hypothesis that excess mitogenic activity for airway smooth muscle cells is present within the lungs of hyperoxia-exposed immature rats. We assessed the proliferative effect of bronchoalveolar lavage (BAL) fluid from air- and O2-exposed animals on cultured rat tracheal smooth muscle cells. BAL fluids from air- or O2-exposed immature rats increased DNA synthesis ([3H]-thymidine incorporation at 24 h of incubation) and cell number (compared with DMEM-treated control cells, at 2 days of incubation), but BAL fluid from O2-exposed animals had significantly greater mitogenic effects. This excess mitogenic activity was lipid inextractable and was ablated by trypsin digestion, indicating that at least one polypeptide growth factor was responsible; molecular sieve fractionation demonstrated a molecular weight of > 10 kD. Because platelet-derived growth factor (PDGF) has been identified in other models of hyperoxia exposure, we tested the further hypothesis that PDGF contributes to the observed excess mitogenic activity. Addition of neutralizing anti-PDGF antibodies to BAL-stimulated smooth muscle cultures did not reduce BAL fluid-induced mitogenesis. These data indicate that the lungs of O2-exposed rats contain excess mitogenic activity for airway smooth muscle, attributable to non-PDGF polypeptide growth factors. It is conceivable that this abnormal mitogenic activity contributes to O2-induced airway smooth muscle remodeling observed in immature rats in vivo.
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PMID:Bronchoalveolar lavage fluid from immature rats with hyperoxia-induced airway remodeling is mitogenic for airway smooth muscle. 787 92

The herbicide, paraquat is highly toxic for mammals, with the lungs being the main target organ, because of the active accumulation of the compound in this organ. The cellular toxicity of paraquat has been shown to be an O2-driven process and hyperoxia is known to increase the lethality of paraquat. In this study we have examined the effect of various O2 concentrations on the toxicity of paraquat in rat and human type II pneumocytes in culture, and we have tested whether the thickness of the liquid layer above the cells would influence the toxicity of paraquat. Type II pneumocytes were isolated from rat or human lung tissue using trypsin digestion, percoll density gradient centrifugation and differential attachment. Adherent cells (day 2) were incubated for 20 h in different volumes of culture medium (thickness of liquid layer), whether or not in the presence of paraquat, in the presence of different O2 tensions. The viability of the cells was assessed by the release of LDH in the culture medium. In both rat and human type II pneumocytes the toxicity of paraquat was independent of the thickness of the liquid layer (2.5 to 10 mm height). The toxicity of paraquat in rat type II pneumocytes decreased from a TC50 value of 28 microM paraquat at 21% O2 to 107 microM at 10% O2 and increased to 12 microM and 8 microM at 60% and 85% O2, respectively. For human type II pneumocytes the TC50 values were 7 microM; 25 microM and > 1000 microM paraquat at 60%, 21% and 10% O2, respectively. In this study we have shown that the diffusion of O2 through a liquid layer does not limit the toxicity of paraquat and that, as in vivo, increasing O2 partial pressure enhances the toxicity of paraquat.
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PMID:Effects of oxygen pressure and medium volume on the toxicity of paraquat in rat and human type II pneumocytes. 921 25

Acute lung injury is marked by damage to alveolar-capillary barrier. High pulmonary levels of matrix-degrading serine proteinase trypsin and matrix metalloproteinases (MMP)-2, -8, and -9 have been shown in preterm infants with respiratory distress syndrome (RDS). We studied expression of trypsin and MMP-2, -8, and -9 in rats exposed to >95% oxygen for 24, 48, or 60 h. As demonstrated by zymography and Western immunoblotting, levels of trypsin and MMP-2, -8, and -9 in bronchoalveolar lavage fluid (BALF) sharply increased after 48 h of hyperoxia relative to normoxia controls. This coincided with increase in alveolar-capillary permeability, as indicated by increased protein concentration in BALF. Both neutrophil-derived 80-kD and mesenchymal cell-derived 60-kD MMP-8 isoforms were detected in BALF. Of them, mesenchymal-type MMP-8 predominated. In immunohistochemistry, alveolar epithelium showed strong trypsin expression at 48 and 60 h of hyperoxia, whereas it was predominantly negative in controls. MMP-8 was mostly expressed in macrophages. Marked up-regulation of trypsin and MMP-8 early during hyperoxic lung injury suggests that these enzymes play a role in the pathogenesis of acute lung injury and may therefore be potential targets for therapy of lung injury.
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PMID:Up-regulation of trypsin and mesenchymal MMP-8 during development of hyperoxic lung injury in the rat. 1694 Feb 37

Pigment epithelium derived factor (PEDF) is an endogenous inhibitor of angiogenesis. However, its physiological role during vascular development and neovascularization remains elusive. Here we investigated the role of PEDF in normal postnatal vascularization of retina and retinal neovascularization during oxygen-induced ischemic retinopathy (OIR) using PEDF-deficient (PEDF-/-) mice. The beta-galactosidase staining of eye sections from PEDF-/- mice confirmed the expression pattern of endogenous PEDF previously reported in mouse retina. However, strongest staining was observed in the retinal outer plexiform layer. Retinal trypsin digests indicated that the ratio of endothelial cells (EC) to pericytes (PC) was significantly higher in PEDF-/- mice compared to wild type (PEDF+/+) mice at postnatal day 21 (P21). This was mainly attributed to increased numbers of EC in the absence of PEDF. There was no significant difference in the number of PC. We observed an increased rate of proliferation in retinal vasculature of PEDF-/- mice, which was somewhat compensated for by an increase in the rate of apoptosis. Staining of the retinal wholemounts and eye frozen sections indicated postnatal retinal vascularization expansion occurred at a faster rate in the absence of PEDF, and was more prominent at early time points (prior to P21). The retinal vascularization in PEDF+/+ mice reaches that of PEDF-/- mice such that no significant difference in vascular densities was observed by P42. Lack of PEDF had a minimal effect on the regression of hyaloid vasculature and VEGF levels. PEDF-/- mice also exhibited enhanced sensitivity to hyperoxia-mediated vessel obliteration during OIR compared to PEDF+/+ mice despite higher levels of VEGF. However, there was no significant difference in the degree of retinal neovascularization. Our studies indicate that PEDF is an important modulator of early postnatal retinal vascularization and in its absence retinal vascularization proceeds at a faster rate and is more susceptible to hyperoxia-mediated vessel obliteration.
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PMID:PEDF-deficient mice exhibit an enhanced rate of retinal vascular expansion and are more sensitive to hyperoxia-mediated vessel obliteration. 1860 15

Extensive activation of mast cells is the major switch that triggers systemic anaphylaxis, resulting in the subsequent release of anaphylactic mediators into circulation. We previously demonstrated that rapid changes in oxygen tension lead to mast cell degranulation, and the released tryptase triggers retinal angiogenesis in a murine oxygen-induced retinopathy model. However, whether a rapid shift from hyperoxia to normoxia (relative hypoxic stress) is a risk factor for systemic anaphylaxis remains unknown. In this study, we demonstrated that the relative hypoxia stress induces systemic mast cell activation via transient receptor potential ankyrin 1 (TRPA1) channels, which immediately leads to hypothermia and increased vascular permeability in adult mice. Although mast cell-deficient or TRPA1-deficient mice did not exhibit anaphylactic symptoms following a rapid sift to normoxia, preinjection with bone marrow-derived cultured mast cells (BMCMCs) derived from wild-type TRPA1-expressing mice restored anaphylactic responses. In addition, we found that the rapid reductions in oxygen tension in a culture atmosphere triggered the degranulation of BMCMCs derived from wild-type TRPA1-expressing mice but not that of BMCMCs derived from TRPA1-deficient mice. In human LAD2 mast cells, the relative hypoxic stress led to the degranulation, which was suppressed by the addition of a TRPA1 inhibitor. Gradual reductions from hyperoxia to normoxia led to no anaphylactic symptoms. Our results demonstrated that TRPA1-triggered mast cell degranulation is a novel pathway that induces anaphylactic shock without Ag-Ab reactions. These findings introduce a potential role for oxygen in inducing mast cell-dependent anaphylaxis and highlight the need to reconsider chronic pure oxygen therapy for anoxic diseases.
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PMID:A Rapid Shift from Chronic Hyperoxia to Normoxia Induces Systemic Anaphylaxis via Transient Receptor Potential Ankyrin 1 Channels on Mast Cells. 3309 73