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Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although the pathogenesis of asbestos-induced pulmonary damage is still not completely understood, an important role has been attributed to active oxygen species. In the present paper we present results of a study investigating the effect of crocidolite asbestos inhalation on different lung antioxidant enzymes in rats. During the development of pulmonary fibrosis induced by crocidolite asbestos, lung superoxide dismutase, catalase and selenium-dependent glutathione peroxidase activities increased, indicating an adaptive response to increased pulmonary oxidant stress. However, this adaptive response obviously is not sufficient to protect the lung from asbestos-induced pulmonary damage. Considering the role of active oxygen species in both the fibrotic process and tumor promotion, it is hypothesized that antioxidants may also protect the lung from chronic asbestos-induced pulmonary damage such as bronchogenic carcinoma.
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PMID:Increases in endogenous antioxidant enzymes during asbestos inhalation in rats. 196 19

Asbestos exposure causes chronic interstitial pulmonary fibrosis. Injury to human pulmonary epithelial cells (HPEC) is speculated to precede the fibrotic response. We investigated whether asbestos, either alone or in conjunction with serum, injured cultured HPEC as assessed in a standard chromium 51 release assay. Amosite asbestos in serum-free media induced modest HPEC injury (9.4% +/- 3.3% Cr release), which was significantly enhanced (2.7-fold) in the presence of serum (25.5% +/- 4% Cr release). HPEC cytotoxicity was both asbestos and serum dose-dependent. Additionally, we demonstrated that, compared with HPEC injury induced by asbestos plus serum, (1) heat-decomplemented serum or serum fractions of a wide range of molecular weights were equipotent to fresh serum, (2) catalase, superoxide dismutase, or dimethylthiourea was not protective, (3) 3-aminobenzamide, which prevents oxidant-induced adenosine triphosphate depletion by inhibiting poly-adenosine diphosphate-ribose polymerase, afforded significant protection (32% decrease in HPEC injury), and (4) deferoxamine-treated asbestos was significantly less toxic to HPEC compared with untreated asbestos, causing a 57% decrease in HPEC cytotoxicity. Electron microscopic studies revealed that, compared with buffer, serum increased the amount of amosite asbestos along the surface and inside HPEC. Thus, amosite asbestos is cytotoxic to cultured HPEC and serum promotes this injurious effect by augmenting the interaction of asbestos with HPEC. These data suggest that this effect may occur by increasing intracellular oxidant stress mediated in part by the iron in asbestos.
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PMID:Serum promotes asbestos-induced injury to human pulmonary epithelial cells. 211 12

The activities of three enzymes cytosolic superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSHP), and malonyldialdehyde (MDA), a by-product of lipid peroxidation, were determined in whole lungs of normal and bleomycin-treated rats. Two days after bleomycin treatment total lung SOD, CAT, and GSHP activities were significantly (p less than .025) depressed between 15 and 25%. The activities of all three enzymes increased 4 days after bleomycin treatment with only SOD significantly increased at days 4 and 7. Total lung CAT activity remained near normal levels while GSHP activity increased only at day 28 (160.5%, p less than .01) indicating a specificity of the response of lung SOD and GSHP levels. Total lung MDA levels were increased by 17% at 2 and 4 days (p less than .05) after bleomycin treatment, and returned to normal levels at 7 and 28 days. These data suggest that impairment of the lung's ability to detoxify O2 metabolites may play an important role in the development of bleomycin-induced pulmonary fibrosis.
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PMID:Oxygen metabolite detoxifying enzyme levels in bleomycin-induced fibrotic lungs. 245 74

Reactive oxygen species (ROS) have been closely associated with a number of pathological disorders, including interstitial pulmonary fibrosis. While models of ROS-induced fibrosis offer advantages over chemically-induced fibrosis, the biochemical and morphological features of ROS-induced fibrosis have yet to be extensively documented. In this study, we evaluated the effect of initial ROS dose on lung injury and repair. Male hamsters received a single dose of glucose, glucose oxidase and lactoperoxidase via the intratracheal route. From 3 to 14 days post-treatment, a significant dose-related body weight loss was observed. There was a trend towards greater mortality with increasing dose. After 2 weeks, we noted significant, dose-related increases in lung levels of collagen, lipid peroxidation products, nucleic acids, and protein. Similarly, total lung catalase, lactic dehydrogenase and glutathione reductase activities were also elevated significantly above control values in a dose-related fashion. A concurrent, dose-dependent thickening of alveolar septa in ROS-treated lungs was composed of epithelial hyperplasia, hyperemia, edema and accumulations of interstitial fibers and macrophages. Interstitial and alveolar macrophages in ROS-induced lesions were enlarged and contained numerous primary and secondary lysosomes. These results demonstrate that, in the hamster lung, injury induced by enzyme-generated ROS can initiate dose-dependent fibroproliferative changes which eventuate into interstitial fibrosis.
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PMID:Dose-related effects of enzyme-generated oxidants on the biochemistry and morphology of the hamster lung. 267 4

Cell injury and inflammation caused by asbestos are critical to the pathogenesis of pulmonary fibrosis (asbestosis). Our goal in studies here was to investigate the possible modulation of asbestos-related cell death using antioxidants in both target and effector cells of asbestosis. After exposure to crocidolite asbestos at a range of concentrations (2.5-25 micrograms/cm2 dish), the viability of a normal rat lung fibroblast line (RL-82) and freshly isolated alveolar macrophages (AM) was determined by exclusion of trypan blue and nigrosin, respectively. In comparison to fibroblasts, AM were more resistant to the cytotoxic effects of asbestos. Cytotoxic concentrations of asbestos then were added to both cell types in combination with the antioxidants, superoxide dismutase (SOD), a scavenger of superoxide (O2-.), and catalase, an enzyme scavenging H2O2. Dimethylthiourea (DMTU), a scavenger of the hydroxyl radical (OH.) and deferoxamine, an iron chelator, also were evaluated in similar studies. Results showed significant dosage-dependent reduction (P less than 0.001) of asbestos-associated cell death with all agents. In contrast, asbestos-induced toxicity was not ameliorated after addition of chemically inactivated SOD and catalase or bovine serum albumin. Results above suggest asbestos-induced cell damage is mediated by active oxygen species. In this regard, the iron associated with the fiber and/or its interaction with cell membranes might be critical in driving a modified Haber-Weiss (Fenton-type) reaction resulting in production of OH(.).
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PMID:Prevention of asbestos-induced cell death in rat lung fibroblasts and alveolar macrophages by scavengers of active oxygen species. 311 71

Current evidence suggests that bleomycin toxicity may be attributable to its DNA degradative activity possibly via generation of free radicals and O2 metabolites as mediators. Since lipopolysaccharide (LPS) has been known to provide protection against O2 toxicity, which is correlated with increased activity of O2 metabolite-detoxifying enzymes, the effect of this agent on bleomycin-induced pulmonary fibrosis was examined. Endotracheal bleomycin administration caused increased lung collagen synthesis. A single intraperitoneal injection of LPS (500 micrograms/kg) at day zero significantly decreased these increases. Total bleomycin-induced lung collagen increase was also significantly reduced. LPS alone had no significant effect on total lung catalase activity. Glutathiione peroxidase activity, however, was significantly decreased by 15.8% compared to untreated animals at 2 days after LPS treatment and remained unchanged at other time points. In addition, superoxide dismutase activity was significantly elevated by 30% above untreated animals only at 14 days after LPS administration and remained unchanged at other time points. Endotracheal bleomycin administration alone caused significant reductions in catalase activity at 2 days and 2 weeks after treatment, whereas glutathione peroxidase activity increased above control untreated animals at 2 and 4 weeks, respectively. Superoxide dismutase activity was unaffected by bleomycin treatment. Pretreatment with LPS before bleomycin prevented these reductions or caused increases in the activities of these enzymes at 2 days. Glutathione peroxidase was increased and was significantly greater than those animals treated with bleomycin alone. Catalase also was higher in the LPS plus bleomycin group (by 22.2%, p less than 0.05) than the bleomycin group alone. Compared to the effects on lung collagen synthesis and content, LPS treatment resulted in much less dramatic changes in total lung antioxidant enzyme activities. This discrepancy between the intensity of LPS effects on lung O2 metabolite-detoxifying enzymes and that on pulmonary fibrosis implies that the LPS-ameliorating effect on pulmonary fibrosis could not be totally explained by increased ability to detoxify O2 metabolites. Rather, the data would favor the possibility that LPS inhibits bleomycin-induced pulmonary fibrosis either by its known immunosuppressive effects or some other unknown mechanism. The former would be in agreement with previous data which suggest that an intact immune response is necessary for complete expression of the fibrogenic response to bleomycin.
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PMID:Inhibition of bleomycin-induced pulmonary fibrosis by lipopolysaccharide. 620 76

The pulmonary fibrosis caused by peplomycin (PEP) was studied in terms of oxygen toxicity using ICR mice. When 16 micrograms of PEP was administered intratracheally in mice after exposure to the air containing 75% O2 for 10 days, the pulmonary fibrosis was completely suppressed, while when mice were exposed to 75% O2 after the administration of PEP, the fibrosis was much severe than that of mice raised in atmospheric air. In 50% O2, similar oxygen effect was also observed, but it was weaker than that in 75% O2. In 90% O2, the oxygen toxicity was observed in mice without administration of PEP. When mice were exposed to 75% O2, the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, which are relevant to the detoxication of active oxygen species, were not increased in the lung, but the levels of reducing agents such as glutathione and ascorbic acid, and high molecular substances having 1O2-scavenging activity were enhanced. The results suggest that these materials have some roles to decrease the pulmonary fibrosis caused by PEP.
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PMID:Effect of oxygen concentration on pulmonary fibrosis caused by peplomycin in mice. 620 63

Regenerating areas of human lungs in pulmonary fibrosis were observed electron microscopically, and peroxidatic activity of catalase in lung peroxisomes were demonstrated cytochemically. Proliferation of Type II cells was prominent there, and some of the cells extended their cytoplasms to cover the denuded basement membrane. Unusual intermediate cells between Type II and Type I cells were observed. The extension of cytoplasmic processes with new generation of pinocytotic vesicles strongly suggested a Type I cell profile. However, catalase-positive peroxisomes were found in these cells simultaneously. From these results it was concluded that Type I cells may originate from Type II cells in human lungs as they do in experimental animals.
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PMID:Differentiation of human pulmonary alveolar epithelial cells revealed by peroxisome changes in pulmonary proteinosis. 670 95

The intrapulmonary instillation into rat lung of enzymes that generate oxygen metabolites results in acute lung injury. The injection of xanthine oxidase and xanthine produces acute lung injury that, in the presence of superoxide dismutase, but not in the presence of catalase, can be significantly diminished, suggesting that O2- has the capacity to injure the lung. Instillation of a generator of H2O2, namely glucose oxidase, will, in sufficient quantities, produce acute injury that is not neutrophil-dependent. When either a low dose of glucose oxidase alone or lactoperoxidase alone is employed, little lung injury occurs. However, instilling the combination of the two enzymes produces severe, acute injury that can be blocked in a dose-dependent manner by catalase, but not by superoxide dismutase. Purified human leukocytic myeloperoxidase, but not horseradish peroxidase, will substitute for lactoperoxidase in the model of lung injury. The lung damaging effects of these enzymes cannot be attributed to the presence of contaminating proteases. Acute lung injury produced by the instillation of glucose oxidase and lactoperioxidase progresses to interstitial fibrosis. These studies represent a direct application of generators of oxygen metabolites to the in vivo induction of lung injury. The data suggest that rat lung is susceptible to injury by a variety of oxygen metabolites, including O2-, H2O2 and its lactoperoxidase or myeloperoxidase-produced derivatives. The studies also indicate that lung injury produced by oxygen metabolites can result in interstitial pulmonary fibrosis.
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PMID:In vivo damage of rat lungs by oxygen metabolites. 689 54

Studies have implicated active oxygen species (AOS) in the pathogenesis of various lung diseases. Many chemical and physical agents in the environment are potent generators of AOS, including ozone, hyperoxia, mineral dusts, paraquat, etc. These agents produce AOS by different mechanisms, but frequently the lung is the primary target of toxicity, and exposure results in damage to lung tissue to varying degrees. The lung has developed defenses to AOS-mediated damage, which include antioxidant enzymes, the superoxide dismutases [copper-zinc (CuZnSOD) and manganese-containing (MnSOD)], catalase, and glutathione peroxidase (GPX). In this review, antioxidant defenses to environmental stresses in the lung as well as in isolated pulmonary cells following exposure to a number of different oxidants, are summarized. Each oxidant appears to induce a different pattern of antioxidant enzyme response in the lung, although some common trends, i.e., induction of MnSOD following oxidants inducing inflammation or pulmonary fibrosis, in responses to oxidants occur. Responses may vary between the different cell types in the lung as a function of cell-cycle or other factors. Increases in MnSOD mRNA or immunoreactive protein in response to certain oxidants may serve as a biomarker of AOS-mediated damage in the lung.
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PMID:Regulation of antioxidant enzymes in lung after oxidant injury. 752 4


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