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

Bleomycin, an important cause of pulmonary fibrosis, is known to produce DNA damage. The mechanism for this damage in vitro is related to free radical production by a bleomycin and iron complex. To determine whether bleomycin causes damage to DNA in vivo by a similar mechanism, we used a viral minichromosome that is replicated in cultured cells. Bleomycin causes dose-dependent damage to intracellular DNA, and this damage is augmented by Fe2+ but not Fe3+. The augmentation of the bleomycin-induced DNA damage caused by Fe2+ is also dose dependent in that increasing DNA damage occurs with increasing amounts of Fe2+. These studies demonstrate that bleomycin causes damage to DNA in vivo and suggest that bleomycin must rely on Fe2+ to donate an electron for oxygen radical-induced DNA strand scission.
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PMID:Augmentation of bleomycin-induced DNA damage in intact cells. 248 Jul 14

In a random screening of camel diseases in Somalia dust-laden macrophages in lungs and/or bronchial lymph nodes were discovered in 94 of 134 animals. In 44 cases the dust-laden macrophages occurred in a number of small or large aggregates. There was a significant positive correlation between dust-laden macrophage aggregates in the lungs and pulmonary fibrosis not related to other chronic lung diseases, such as echinococcosis and chronic pneumonia. Six cases showed a cellular reaction and hyalinized nodules of the classic silicotic type. Energy dispersive X-ray analysis of the dust particles revealed presence of silica, aluminium, potassium and iron in that order. The possible clinical significance as well as the comparative pathology of the observations is discussed.
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PMID:Silicate pneumoconiosis in camels (Camelus dromedarius L.). 251 89

Serum copper (Cu) concentration was evaluated as an index of lung injury in two rat models of pneumotoxicity: hemithoracic irradiation and monocrotaline ingestion. In both models there was a dose- and time-dependent increase in serum Cu concentration. This hypercupremia paralleled the development of pulmonary endothelial dysfunction (decreased lung plasminogen activator activity and increased prostacyclin production) and pulmonary fibrosis (hydroxyproline accumulation). In the radiation model, lung injury and hypercupremia persisted for at least 6 months, and were spared similarly when the total dose was delivered in multiple daily fractions as compared to single doses. In irradiated rats, the elevated serum Cu concentration was accompanied by increases in plasma ceruloplasmin, lung Cu concentration, and lung Cu/Zn superoxide dismutase (SOD) activity. In monocrotaline-treated rats, lung damage and hypercupremia also were accompanied by a reduction in liver Cu concentration, and by a direct correlation between the concentrations of Cu and SGOT in the serum. In both models, some but not all modifiers of lung damage (penicillamine, angiotensin converting enzyme inhibitors, pentoxifylline) also partially prevented the insult-induced hypercupremia. In contrast, serum iron concentration was largely independent of treatment in all experiments. These data suggest that elevated serum copper concentration is an accurate and minimally invasive index of lung injury in irradiated and monocrotaline-treated rats.
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PMID:Serum copper concentration as an index of experimental lung injury. 251 9

Bleomycin is a commonly used antineoplastic compound that can produce a dose- and time-dependent pneumonitis and fibrosis in humans. The mechanism of bleomycin-induced fibrosis is not known. However, current data suggest that the production of oxygen radicals by way of a ferrous ion-molecular oxygen mechanism might be related to the pulmonary fibrosis. Therefore, we evaluated the possibility that parenterally administered deferoxamine, an iron chelating compound, could modulate the morphologic and biochemical estimates of bleomycin-induced lung fibrosis in hamsters. Deferoxamine pretreatment and daily injection for 21 days after intratracheally administered bleomycin resulted in a 33% reduction in lung collagen accumulation compared with that after bleomycin treatment alone. However, fibrosis was still present in the bleomycin-deferoxamine group; the animals showed a 142 and 150% increase in lung collagen compared with that in saline- and deferoxamine-treated control animals, respectively. Morphologic estimates of the severity of fibrosis in the bleomycin-deferoxamine treatment group were reduced when compared with the bleomycin treatment group alone, but was increased compared with saline- and saline-deferoxamine-treated control animals. These data indicate that deferoxamine treatment reduces the severity of bleomycin-induced pulmonary fibrosis in hamsters. The mechanism might be by the prevention of iron-catalyzed, free-radical formation.
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PMID:The effect of deferoxamine on bleomycin-induced lung fibrosis in the hamster. 258 89

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

Histological examination on lung tissue obtained from 10 symptomatic welders was performed by two certified pathologists without the knowledge of the patients' clinical condition. In all cases, there was some degree of interstitial fibrosis; in five the degree of fibrosis was considered to be moderate to pronounced. The tissue was also analysed by energy dispersive x ray analysis and elemental contents were compared with age matched controls. There was a large amount of iron in the lungs of welders but the silicon content did not differ from the control subjects. No specific foreign element was detected. It is concluded that (1) interstitial pulmonary fibrosis is seen in some welders and (2) the cause of fibrosis does not appear to be coexisting silicosis.
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PMID:Welders' pneumoconiosis: tissue elemental microanalysis by energy dispersive x ray analysis. 334 82

Changes of 67Ga uptake in the lungs and changes of components of the so-called ground substance of the lung connective tissues of mice were followed for 7 weeks after the start of bleomycin (BLM) administration (20 mg/kg body weight IP, twice weekly for 5 weeks; this treatment induced fibrosis of the lung). 67Ga uptake of the lung was elevated at 1 week, and reached a maximum at 5 weeks (3.00 +/- 0.11% dose/g lung), and then decreased slightly at 7 weeks. The uronic acid content in the 1.2 M NaCl-soluble fraction, which contained predominantly heparan sulfate (HS), was increased at 1 week, peaked at 3 weeks, and then remained unchanged up to 7 weeks. This pattern was similar to that of 67Ga accumulation in the lungs. The uronic acid content of the 0.4 M NaCl-fraction, which contained predominantly hyaluronic acid (HA), was decreased at 1 week, but increased to a maximum at 3 weeks, then decreased to about the initial level at 5 weeks and decreased further at 7 weeks. Lung hydroxyproline content, an index of collagen content, was increased at 3 weeks and continued to increased rapidly thereafter, reaching approximately 1.5 times the control value at 7 weeks. Serum iron, measured as an indicator of iron metabolism, was slightly increased at 3 weeks and there was a corresponding decrease of unsaturated iron-binding capacity (UIBC). No corresponding change of 67Ga uptake was apparent. These results indicate that HS increased before the collagen accumulation at an early stage of pulmonary fibrosis of the lung during BLM treatment of mice, and support our earlier proposal that HS is a major acceptor for 67Ga accumulation.
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PMID:Uptake of 67Ga in the lung of mice during bleomycin treatment. 620 Mar 25

Fibers of the amphibole mineral series have been demonstrated in the dust from an open taconite ore mine. Though the total dust levels in some places are high, exposures to fibers are below one fiber/cc. The energy dispersive X-ray spectra of the amphibole fibers correspond to those of cummingtonite-grunerite, hornblende, or actinolite. The same type and size distribution of fibers were found during post mortem analyses of lung tissue from two previously exposed miners. The pathological examination revealed an undifferentiated small cell carcinoma of left lung as well as pulmonary fibrosis in one of the cases. In the second case a poorly differentiated squamous cell carcinoma of left lung was found along with silicosis.
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PMID:Amphibole fibers in a taconite mine and in the lungs of the miners. 629 43

IPH is an uncommon disease affecting mainly children and adults and has usually a poor prognosis. The basic pathogenesis of the disorder is unknown; many theories have been advanced, but none is proved. A case of IPH in a 35 years old male presenting the atypical feature of a myeloperoxidase deficiency is reported. This unusual feature may be compatible with a generalized redox systems deficiency, which leads, via an impaired flow of iron into alveolar macrophages, to the pulmonary fibrosis.
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PMID:[Idiopathic adult pulmonary hemosiderosis: a new etiopathogenetic hypothesis]. 665 24

Asbestos causes the fibrotic lung disease asbestosis, but the biologic basis for this is unknown. Lung epithelial dysfunction including increased permeability is hypothesized to contribute to lung scarring in other forms of pulmonary fibrosis. Lung epithelial permeability is increased in both animals and humans exposed to asbestos. It is not known whether the increased epithelial permeability results from direct effects of asbestos or occurs as a result of the inflammatory reaction to asbestos fibers. To address this question we used a cultured human lung epithelial model, and we measured the direct effect of asbestos on lung epithelial barrier integrity as measured by mannitol permeability. We exposed the monolayer to chryogenically ground, respirable-sized chrysotile asbestos particles. This chrysotile asbestos caused a dose- and time-dependent increase in mannitol permeability across the epithelial monolayer. Increased mannitol permeability occurred both in the presence and in the absence of serum, was not due to cytotoxicity as measured by lactate dehydrogenase release, and was not associated with altered actin cytoskeleton at the light microscopic level. Permeability to 70 kDa neutral dextran also increased after asbestos exposure; however, the absolute permeability to dextran was less than mannitol permeability. Neither latex beads nor tantalum caused any change in permeability, suggesting that our findings are not explained by nonspecific effects of particles. Increased permeability did not reverse in the continued presence of asbestos and persisted even after removing the asbestos. Finally, surface-bound iron did not appear to be necessary for this effect because neither chelating iron with deferoxamine nor iron-loading the asbestos altered the effect on mannitol permeability. These results show that asbestos has direct effects on lung epithelial permeability. Together with the recent observation that asbestos directly increases epithelial fibrinolytic activity, our results suggest a novel mechanism for asbestos-induced lung injury.
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PMID:Asbestos directly increases lung epithelial permeability. 769 46


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