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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

In an experimental model of lung metastasis we have observed that more metastatic tumors are located on the pleura of the lung than in the parenchyma. To study possible reasons for this differential pattern we have now related the initial distribution of injected tumor cells to the later location and growth rate of metastases in different regions of the lung in C57bl/6 mice. It was found that labeled murine fibrosarcoma cells were evenly distributed throughout the lungs 24 h after intravenous injection into controls and animals previously treated with bleomycin or by exposure to hyperoxia. These treatments, known to induce pulmonary endothelial injury, were associated with increased tumor cell localization in the lung. In all cases, using morphometric methods, we found that after 2 weeks, approximately 75 per cent of metastatic tumors were located at the pleura. By [3H]thymidine labeling in autoradiographs, pleural tumors in all experimental groups had a growth rate 14 times the growth rate of tumors located in the internal regions of the lung. In vitro, the fibrosarcoma cells proliferated more rapidly on connective tissue matrices prepared from normal pleuras than they did on matrices from the remainder of the lung. Protease digestion of these matrices indicated differences in composition with more insoluble collagen, probably type I collagen, present at the pleura. These data suggest that, in spite of the initial random distribution and localization of tumor cells in the lung, there is preferential growth of metastatic tumors at the pleura which may be related to regional differences in the composition of the extracellular matrix.
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PMID:Preferential growth of metastatic tumors at the pleural surface of mouse lung. 334 65

We used a sensitive hemolytic assay to measure the level of C1q, a subcomponent of the first complement protein in the classic pathway, in bronchoalveolar lavage fluid and serum of rats exposed to air and hyperoxia. The serum level was 125 +/- 5 micrograms/ml and the lavage level was 41 +/- 17 ng/ml in rats breathing air. In rats exposed to acute oxygen toxicity (95% O2 for 66 hr), the serum level was at 107 +/- 10 micrograms/ml, but the level in lavage fluid increased to 2457 +/- 400 ng/ml (p less than 0.05 compared to air). Administration of the proline analogue cis-4-hydroxy-L-proline to air- and O2-exposed rats reduced the serum C1q level by 28% and 34%, respectively (both p less than 0.05), presumably by interfering with metabolism of the collagen-like sequence of C1q. The level of C1q in bronchoalveolar lavage fluid is a sensitive marker of acute lung injury.
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PMID:C1q content of serum and lung lavage fluid of rats exposed to toxic levels of oxygen. 349 Oct 45

The systemic administration of O,S,S-trimethyl phosphorodithioate (OSS), a contaminant of various organophosphorus insecticides, induces delayed damage to rat and mouse lung tissue. The lesion, particularly in the rat, closely resembles that produced by butylated hydroxytoluene (BHT) in mice. Although the time course of cell damage and repair has been studied in both species, it is not clear whether excess collagen, indicative of fibrosis, is deposited. Changes in pulmonary hydroxyproline content and synthesis, indices of collagen metabolism, were analysed in mice treated with 45 mg/kg OSS. A significant increase in total lung hydroxyproline was evident 21 days after treatment compared to both pair-fed and ad libitum controls. This increase was not augmented by subsequent treatment with 35 mg/kg 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or exposure to 70% oxygen for 7 days. The rate at which lung tissue synthesized hydroxyproline was increased 7-14 days after treatment with OSS. These data demonstrate that treatment of mice with OSS results in changes indicative of pulmonary fibrosis. However, in contrast to some other lung-toxic chemicals, this lesion was not enhanced by subsequent treatment with BCNU or hyperoxia.
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PMID:Pulmonary hydroxyproline content and production following treatment of mice with O,S,S-trimethyl phosphorodithioate. 366 Apr 35

We studied damage and repair of lung connective tissue in rats exposed to toxic amounts of oxygen by measuring lung content of collagen and elastin and the number of collagen fragments in lung lavage fluid after exposure to 98% O2 for 60 h. Lung collagen was decreased 17%, and collagen fragments in lavage fluid were increased 4- to 5-fold in O2-exposed rats compared with those in control rats. No biochemical evidence of elastin degradation was found. Mild emphysematous changes and a leftward shift of fluid-filled, pressure-volume curves were induced within 2 wk after recovery from exposure to O2. Administration of the lathyrogen beta-aminopropionitrile worsened the emphysematous lesion produced by hyperoxia, suggesting that replacement of connective tissue during repair limits the extent of emphysema. We conclude that lung collagen is degraded and an emphysematous lesion is produced by relatively short exposure to toxic amounts of oxygen.
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PMID:Damage and repair of lung connective tissue in rats exposed to toxic levels of oxygen. 381 7

The intraperitoneal administration of methylcyclopentadienyl manganese tricarbonyl (MMT) and cyclophosphamide, exposure to an aerosol of cadmium chloride, intravenous administration of oleic acid, and intratracheal instillation of bleomycin to young female BALB/c mice or CD/CR rats result in acute lung injury. Pulmonary morphology and lung collagen content were examined in animals treated with these chemicals alone or in combination with an elevated oxygen concentration (80%) in the inspired air. In mice, the development of fibrosis could be significantly enhanced if animals treated with MMT, cadmium chloride, cyclophosphamide, or bleomycin were exposed to 80% oxygen immediately following exposure to these agents. In rats only cyclophosphamide- and bleomycin-induced acute lung injury was potentiated by hyperoxia, resulting in significant enhancement of lung collagen content. The pathogenesis responsible for this differential species response of pulmonary injury to hyperoxia remains to be investigated.
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PMID:Potentiating effects of oxygen in lungs damaged by methylcyclopentadienyl manganese tricarbonyl, cadmium chloride, oleic acid, and antitumor drugs. 618 66

Bleomycin is a primary fibrogenic agent which increases collagen content in a fibroblast system by a direct effect on fibroblasts. A mechanism for the increase in collagen content is an increase in the rate of collagen biosynthesis. This implies alteration of either collagen transcription or translation. Hyperoxia depresses collagen biosynthesis without changing collagen content. This implies that hyperoxia also depresses collagen degradation. The addition of phagocytes (macrophages) to hyperoxically exposed cells increases both collagen content and the rate of collagen biosynthesis. Hyperoxia is therefore a secondary fibrogenic agent. This suggests that mediators released from phagocytes alter collagen transcription or translation.
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PMID:Some implications of augmented collagen levels with bleomycin exposure or hyperoxic exposure of lung fibroblasts: fibrosis as altered phenotypic expression. 620 69

We have previously shown that administration of the antioxidant butylated hydroxytoluene (BHT) to mice produces lung damage that can be markedly potentiated by hyperoxia resulting in pulmonary fibrosis. In the present studies using this model, we show that: (1) in animals treated with BHT-O2, prednisolone given for 12 successive days does prevent excessive collagen accumulation provided lung collagen is measured immediately after terminating steroid therapy, whereas a rebound effect occurs later on; (2) limitation of steroid treatment to the first 6 days after acute lung injury enhances accumulation of collagen, whereas steroids given later, on Days 7 through 12, have an alleviating effect; (3) indomethacin under the conditions described is not an effective treatment.
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PMID:Potentiation of butylated-hydroxytoluene-induced acute lung damage by oxygen. Effects of prednisolone and indomethacin. 662 43

Exposure of rats to high oxygen tensions causes increased collagen content of lungs and alveolar enlargement in 3-6 wk. We tested whether cis-hydroxyproline, a proline analogue that inhibits collagen synthesis, could prevent the collagen accumulation and alveolar enlargement. Rats were exposed to hyperoxia for 60 h and then to room air and hyperoxia for alternate 24-h periods for 11.5 d. Treated oxygen-exposed rats received 200 mg/kg cis-hydroxyproline twice daily over the 14-d exposure period. Control rats breathed room air. Examination of lungs on day 14 showed collagen content of oxygen-exposed lungs to be 48% greater than control (P < 0.05). The collagen content of the treated oxygen-exposed lungs was -12% of control (NS). Total lung volume was 16% greater than control in oxygen-exposed rats (P < 0.05) and 8% greater than control in treated oxygen-exposed rats (NS). Morphometric studies showed alveolar size was greater than control in oxygen-exposed rats (188+/-11 [SE] vs. 143+/-6 mumul [P < 0.05]). Oxygen-exposed, treated rats had a mean alveolar volume of 150+/-7 mumul. Lung pressure-volume curves were significantly shifted to the left of control in the oxygen-exposed rats, whereas the curves of the oxygen-exposed, treated group were identical to control. These data suggest that cis-hydroxyproline prevented the accumulation of collagen in the lungs in pulmonary oxygen toxicity. In addition, there was apparent protection from airspace dilatation and decreased lung elasticity, suggesting that alveolar enlargement after oxygen toxicity is linked to the deposition in lung tissue of new connective tissue fibers.
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PMID:Prevention of collagen deposition following pulmonary oxygen toxicity in the rat by cis-4-hydroxy-L-proline. 698 11

Otitis media represents a continuum of inflammatory stages frequently in association with bacteria and/or endotoxin. Furthermore, the disease is often treated with insertion of ventilation tubes, which causes hyperoxia relative to the physiological state in the tympanic cavity. The present study was undertaken to quantitate the interaction between endotoxin and relative hyperoxia in cultures of rabbit middle ear fibroblasts incubated in normal middle ear gas and atmospheric air, respectively. Growth was monitored by determination of DNA, cell protein and cell division. The synthetic activity was estimated by collagen production. The antioxidant defense was determined by measuring the intra-and extracellular concentrations of superoxide dismutase (SOD). The results demonstrated that hyperoxia significantly impaired the growth of middle ear fibroblasts, which was compensated for by addition of endotoxin stimulating the growth. The collagen synthesis increased significantly in atmospheric air with a synergistic effect of endotoxin. Hyperoxia induced intracellular SOD formation, while endotoxin tended to reduce the synthesis. Finally, exposure to atmospheric air caused significantly larger amounts of reducing agents extracellularly in cultures without endotoxin compared to endotoxin incubated cultures. It is suggested that endotoxin possess both synergistic and antagonistic potential as regards the effects of relative hyperoxia, and that the interaction between endotoxin and hyperoxia may be an important factor in otitis media.
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PMID:The influence of endotoxin upon middle ear fibroblasts cultured in normal middle ear gas and atmospheric air. 782 3


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