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

The effects of oxidative stress on DNA damage and associated reactions, increased polyadenosine diphosphate-ribose polymerase (PARP) activity and decreased nicotinamide adenine dinucleotide (NAD) and adenosine triphosphate (ATP) contents, have been tested in primary cultures of porcine aortic endothelial cells. The cells were treated with 50-500 microM H2O2 for 20 min or 100 microM paraquat for 3 days or were exposed to 95% O2 for 2 and 5 days. The administration of 250-500 microM H2O2 resulted in a marked increase in PARP activity and a profound depletion of ATP and NAD. Although hyperoxia had no effect on PARP activity and reduced only slightly the ATP and NAD stores, it markedly reduced the ability of endothelial cells to increase PARP activity upon exposure to DNase. Paraquat had a similar effect. Human dermal fibroblasts were also exposed to 50-500 microM H2O2 for 20 min or 95% O2 for 5 days. Their response to H2O2 differed from that of endothelial cells by their ability to maintain the ATP content at a normal level. Fibroblasts were also insensitive to the effect of hyperoxia. These results suggest that the oxidant-related DNA damage is a function of the type of oxidative stress used and may be cell-specific.
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PMID:Differential effects of hyperoxia and hydrogen peroxide on DNA damage, polyadenosine diphosphate-ribose polymerase activity, and nicotinamide adenine dinucleotide and adenosine triphosphate contents in cultured endothelial cells and fibroblasts. 250 Apr 51

When the herbicide paraquat (1,1'-dimethyl-4,4'-bipyridylium) was administered to adult rat pulmonary alveolar macrophages (PAM) in primary culture, both a time-dependent and a dose-dependent cytotoxic response (cell death) was observed. An LD50 value of 1 mM was calculated when these cells were exposed to paraquat in vitro for 12 h in Ham's F12 culture medium at 30 degrees C. Cell death was accompanied by the formation of TBA-reactive substances (lipid peroxidation) and was potentiated by hyperoxia (95% O2). In a 95% O2-5% CO2 atmosphere, an LD50 value of 0.1 mM was calculated. In addition, the presence of superoxide dismutase in the culture medium (1700 units/ml) inhibited the cytotoxic response. Since [14C]paraquat was not absorbed into these cells, extracellular superoxide anion radical formation was investigated as the cause of the observed cell death. Paraquat (0.5 mM) was found to stimulate extracellular O-2 generation, from PAM, but only in nonactivated cells. A sevenfold enhancement over the resting rate of radical generation was observed in the presence of paraquat. No increase in the O-2 generation rate of activated macrophages was observed upon the addition of paraquat to the culture medium. These data indicate that paraquat is cytotoxic to the pulmonary alveolar macrophage and further suggest that this cytotoxicity is mediated, at least in part, by an excess, extracellular production of active oxygen species. Implications of these findings with respect to the currently accepted hypothesis of paraquat poisoning in vivo are discussed.
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PMID:Paraquat toxicity in vitro. I. Pulmonary alveolar macrophages. 299 34

Paraquat (PQ) is a herbicide known to generate O2 radicals and to injure lung epithelial cells, leading eventually to pulmonary fibrosis. To test for the possible existence of a direct cytotoxic action of PQ on endothelial cells, we have studied, for up to 5 days, the action of 10(-6) to 10(-4) M PQ on primary cultures of pig aortic endothelial cells and compared these effects to those obtained with exposure to 95% O2-5% CO2. The decrease in DNA and protein content of Petri dishes and the increase in lactate dehydrogenase release were found to depend on PQ concentration and the duration of exposure to PQ. The toxic effects of hyperoxia were intermediate, ranging between those obtained with 10(-5) and 10(-4) M PQ. Hyperoxia and 10(-4) M PQ produced a similar marked inhibition of DNA synthesis after a 1-day period of exposure. Combined exposure to both PQ and hyperoxia resulted in changes comparable to those obtained with hyperoxia alone (decrease in protein and DNA content) or PQ alone (lactate dehydrogenase release). Additive effects were seen only for the inhibition of DNA synthesis. The selenomethionine-related increase in glutathione peroxidase activity had a protective effect against hyperoxia-induced lactate dehydrogenase release but not against PQ induced cytolysis. Finally, shorter exposures to O2 and PQ revealed the existence of a trend toward recovery only for cells exposed to hyperoxia. The prolonged toxic action of PQ could not be related to PQ accumulation and storage by endothelial cells. These studies indicate that PQ can exert a direct, dose-dependent, and prolonged cytotoxic effect on cultured endothelial cells.
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PMID:Direct toxic effects of paraquat and oxygen on cultured endothelial cells. 396 1

Paraquat, a widely used herbicide, causes severe, often fatal lung damage. In vivo studies suggest the alveolar epithelial cells (types I and II) are specific targets of paraquat toxicity. This study used 51Cr-labeled type II cells to demonstrate that paraquat (10-5 M) resulted in type II cell injury in vitro, independent of interacting immune effector agents. With 51Cr release expressed as the cytotoxic index (Cl), type II cell injury was found to accelerate with increasing paraquat concentrations (10(-5) M, 10(-4) M, and 10(-3) M, resulting in a Cl of 12.5 +/- 2.2, 22.8 +/- 1.8, and 35.1 +/- 1.9, respectively). Paraquat-induced cytotoxicity (10(-4) M, with a Cl of 22.8 +/- 1.8) was effectively reduced by catalase 1,100 U/ml (Cl 8.0 +/- 3.2, p less than 0.001), superoxide dismutase, 300 U/ml (Cl 17.4 +/- 1.7, p less than 0.05), alpha tocopherol, 10 micrograms/ml (Cl 17.8 +/- 1.6, p less than 0.05). Paraquat toxicity (10(-3) M) was potentiated in the presence of 95% O2 with an increase in Cl from 31.1 +/- 1.7 to 36.4 +/- 2.3 (p less than 0.05). Paraquat-induced type II cell injury was noted as early as 4 h incubation by electron microscopic evidence of swelling of mitochondrial cristae and dispersion of nuclear chromatin. Thus, this in vitro model indicates that paraquat-induced type II cell injury can be quantified, confirmed by morphologic ultrastructural changes, significantly reduced by antioxidants, and potentiated by hyperoxia.
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PMID:Paraquat-induced injury of type II alveolar cells. An in vitro model of oxidant injury. 673 57