Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pulmonary fibrosis was produced in rats by intratracheal administration of bleomycetin. The development of the fibrous process in the lungs was attended by marked reduction of the zinc content in the tissues of the viscera, plasma, and formed elements of the blood, as well as of corticosterone and testosterone in blood plasma. Respiratory insufficiency is a probable cause of the developing zinc-deficiency which leads to disturbed synthesis of steroid hormones. Injection of exogenous testosterone normalizes partly the level of steroid hormones in the blood, improves the general condition of the animals, and facilitates an increase of body weight.
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PMID:[Content of trace elements and steroid hormones in blood and tissues of internal organs in experimental pulmonary fibrosis induced by intratracheal administration of bleomycetin]. 128 98

The type of lung disease caused by metal compounds depends on the nature of the offending agent, its physicochemical form, the dose, exposure conditions and host factors. The fumes or gaseous forms of several metals, e.g. cadmium (Cd), manganese (Mn), mercury (Hg), nickel carbonyl (Nl(CO)4, zinc chloride (ZnCl2), vanadium pentoxide (V2O5), may lead to acute chemical pneumonitis and pulmonary oedema or to acute tracheobronchitis. Metal fume fever, which may follow the inhalation of metal fumes e.g. zinc (Zn), copper (Cu) and many others, is a poorly understood influenza-like reaction, accompanied by an acute self-limiting neutrophil alveolitis. Chronic obstructive lung disease may result from occupational exposure to mineral dusts, including probably some metallic dusts, or from jobs involving the working of metal compounds, such as welding. Exposure to cadmium may lead to emphysema. Bronchial asthma may be caused by complex platinum salts, nickel, chromium or cobalt, presumably on the basis of allergic sensitization. The cause of asthma in aluminium workers is unknown. It is remarkable that asthma induced by nickel (Ni) or chromium (Cr) is apparently infrequent, considering their potency and frequent involvement as dermal sensitizers. Metallic dusts deposited in the lung may give rise to pulmonary fibrosis and functional impairment, depending on the fibrogenic potential of the agent and on poorly understood host factors. Inhalation of iron compounds causes siderosis, a pneumoconiosis with little or no fibrosis. Hard metal lung disease is a fibrosis characterized by desquamative and giant cell interstitial pneumonitis and is probably caused by cobalt, since a similar disease has been observed in workers exposed to cobalt in the absence of tungsten carbide. Chronic beryllium disease is a fibrosis with sarcoid-like epitheloid granulomas and is presumably due to a cell-mediated immune response to beryllium. Such a mechanism may be responsible for the pulmonary fibrosis occasionally found in subjects exposed to other metals e.g. aluminium (Al), titanium (Ti), rare earths. The proportion of lung cancer attributable to occupation is around 15%, with exposure to metals being frequently incriminated. Underground mining of e.g. uranium or iron is associated with a high incidence of lung cancer, as a result of exposure to radon. At least some forms of arsenic, chromium and nickel are well established lung carcinogens in humans. There is also evidence for increased lung cancer mortality in cadmium workers and in iron or steel workers.
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PMID:Metal toxicity and the respiratory tract. 217 66

Orally administered zinc was studied as a protective antifibrotic agent with respect to experimentally caused lung collagen accumulation in rats. Intraperitoneally injected carbon tetrachloride induced a diffuse alveolar damage with interstitial pulmonary fibrosis, and the morphologic findings suggested a primary toxic effect on the lungs. The carbon tetrachloride induction increased significantly the lung to body weight ratio, lung total protein and collagen content, lung total prolyl hydroxylase and galactosylhydroxylysyl glucosyltransferase activities, and daily urinary hydroxyproline excretion. Treatment with 114 mg/L of zinc in the animals' drinking water inhibited the lung prolyl hydroxylase activity and prevented the increases in lung collagen content and urinary hydroxyproline excretion but did not normalize any of the other above parameters. Enhanced lung prolyl hydroxylase activity was noted when a ferrous ion excess was included in the assay in order to reverse the competitive inhibition of the enzyme activity by zinc. It is suggested that zinc has a direct and selective preventive effect on rat lung collagen accumulation by inhibiting procollagen proline hydroxylation.
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PMID:Prevention by zinc of rat lung collagen accumulation in carbon tetrachloride injury. 299 29

A thermolysin-like metalloendopeptidase, optimally active at a neutral pH, was identified in human serum. The enzyme cleaves the synthetic substrate glutaryl-Ala-Ala-Phe-2-naphthylamide at the Ala-Phe bond. Activity was determined by measuring the rate of formation of Phe-2-naphthylamide in a coupled enzyme assay in the presence of excess aminopeptidase M. 2-Naphthylamine released during the reaction was determined by a diazotization procedure. Enzyme activity is not affected by inhibitors of serine, thiol, or carboxyl proteases, but is sensitive to inhibition by metal chelators such as EDTA and o-phenanthroline. Dialysis against EDTA leads to loss of activity, which can be fully restored by zinc and cobalt ions. The serum enzyme closely resembles a membrane-bound metalloendopeptidase (EC 3.4.24.11) abundant in lung, spleen, and kidney in that both enzymes are inhibited by the same active-site-directed inhibitors. In addition, an antiserum obtained against the metalloendopeptidase from rabbit kidney shows strong cross-reactivity with the serum enzyme. Metalloendopeptidase activity was measured in 150 controls and in 95 patients with sarcoidosis; the two groups had significantly different enzyme activities (p less than 0.001). The mean enzyme activity in the sarcoidosis group was more than threefold higher than that of the control group. The mean enzyme activity for patients with active disease was more than double that of patients with inactive disease and more than four times that of controls (p less than 0.001). This is noteworthy because angiotensin converting enzyme, a zinc-dipeptidyl carboxypeptidase with a mechanism of action similar to that of the metalloendopeptidase, has also been reported to be increased in the serum of patients with active sarcoidosis. Enzyme activity in patients with active tuberculosis, primary pulmonary neoplasms, and idiopathic interstitial pulmonary fibrosis did not differ significantly from that of controls.
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PMID:Identification of a thermolysin-like metalloendopeptidase in serum: activity in normal subjects and in patients with sarcoidosis. 636 93

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

Biochemical and molecular markers of inflammation, cell proliferation, and pulmonary fibrosis were studied in lungs and bronchoalveolar lavage preparations from Fischer 344 rats at time periods from 3 to 20 days after inhalation of two airborne concentrations (0.18 and 8.2 mg/m3 air) of chrysotile asbestos. Additional groups of animals were examined for lung histopathology and cell proliferation with an antibody to 5-bromo-2'-deoxyuridine after exposure to asbestos for 5 and 20 days and after 20 days of exposure followed by an additional 20 days in room air. Exposure to chrysotile at the higher concentration caused protracted increases in steady-state mRNA levels of manganese-containing superoxide dismutase and elevation in glyceraldehyde-3-phosphate dehydrogenase mRNA at 3 days, but levels of mRNAs encoding copper-zinc-containing superoxide dismutase, ornithine decarboxylase, and the proto-oncogene, c-jun were not statistically elevated from levels occurring in lung homogenates from sham control rats. Differential cell counts in bronchoalveolar lavage revealed an early infiltration of neutrophils that correlated with focal areas of increased cellularity and fibrosis in rat lungs at the higher concentrations of asbestos. However, elevations in lung hydroxyproline were not observed. Significant increases in epithelial cells of the bronchi, the interstitial compartment of the lung, and mesothelial cells incorporating 5-bromo-2'-deoxyuridine, an indication of DNA synthesis, were noted in the higher chrysotile group at 5 days, but labeling in all cell compartments was comparable with that occurring in sham controls at later time points. Indicators of inflammation, increased cell proliferation, and pulmonary fibrosis were not observed in the lungs of rats exposed to the lower concentration of chrysotile. Thus, results indicate that cellular and molecular markers of inflammation and proliferation in lung are dose-related and indicative of the histopathological development of asbestosis.
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PMID:Patterns of inflammation, cell proliferation, and related gene expression in lung after inhalation of chrysotile asbestos. 767 84

Steady-state mRNA levels and immunoreactive protein for manganese-containing superoxide dismutase (MnSOD) were assayed in rat lungs after subchronic inhalation of the fibrogenic silicon dioxide, cristobalite, or preparations of titanium dioxide (TiO2) of different inflammatory and fibrogenic potential. Total and differential cell counts recoverable by bronchoalveolar lavage (BAL) were also measured to ascertain whether induction of certain antioxidant enzymes (AOE) correlated with inflammatory responses. Inhalation of cristobalite and ultra-fine TiO2, a particle causing pulmonary inflammation and fibrosis, caused dramatic increases in MnSOD mRNA levels in rat lung which correlated with increases in MnSOD immunoreactive protein. Increases in gene expression of other AOE [catalase, glutathione peroxidase (GPX), copper-zinc containing superoxide dismutase (CuZnSOD)] were less striking and did not correlate precisely with inflammatory potential of minerals. Inflammatory changes in BAL correlated directly with steady-state MnSOD mRNA levels in lung. Inhalation of TiO2-F, a noninflammatory, nonfibrogenic mineral, failed to induce MnSOD or mRNAs for other AOE. Our data suggest that particles causing inflammation and pulmonary fibrosis increase expression of AOE in lung, most notably MnSOD. Thus, elevations of MnSOD mRNA levels in lung or BAL may be predictive of lung disease.
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PMID:Increased expression of manganese-containing superoxide dismutase in rat lungs after inhalation of inflammatory and fibrogenic minerals. 806 94

The clinical development of dexrazoxane (DEX; ICRF-187; Zinecard, Pharmacia and Upjohn, Kalamazoo, MI) was originally begun using it as an antineoplastic agent. It had a unique mechanism of action and activity in a variety of in vitro and in vivo models. Phase I trials with the agent began in January 1979. The phase I trials indicated that DEX could be safely administered, with leukopenia and thrombocytopenia being the dose-limiting toxicities, on a number of different schedules of administration. Some hints of antitumor activity were also noted. In the phase I studies it was also noted, based on the chelating abilities of DEX, that the compound caused marked increases in urine clearance of iron and zinc in patients receiving the agent. That information, plus the information being generated in preclinical studies that DEX could protect against the cardiotoxicity induced by anthracyclines (through a decrease in free radical formation), led to the use of DEX as a cardioprotective agent (as thoroughly discussed in this supplement). However, in addition to working as a cardioprotective agent, DEX has other potential applications that are outlined below and include (1) treatment of patients with acquired immunodeficiency syndrome-related Kaposi's sarcoma, based on its activity as an angiogenesis inhibitor; (2) enhancement of the effects of cisplatin, based on its ability to increase the antiproliferative effects of cisplatin on human ovarian cancer cells; (3) use for treatment of iron overload states in patients who are allergic to deferoxamine; (4) treatment of patients with psoriasis; (5) protection from hyperoxic effects on the lungs; (6) protection from bleomycin-induced pulmonary fibrosis; (7) attenuation of acetaminophen-induced hepatotoxicity; (8) prevention of mucositis; and (9) other applications. Clearly, there should be additional investigations to maximize the usefulness of the very interesting DEX molecule.
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PMID:Phase I trials of dexrazoxane and other potential applications for the agent. 976 21

We report a case of pulmonary fibrosis in a 32-year-old man, who had worked at a steel mill and who died of respiratory failure due to interstitial fibrosis despite vigorous treatment. He showed SLE-associated symptoms, such as pleural effusion, malar rashes, discoid rashes, arthritis, leukopenia, and positive antinuclear antibody and anti-histone antibody. However, he did not present anti-DNA antibody. A thoracoscopic lung biopsy showed interstitial fibrosis, chronic inflammation and a small non-caseating granuloma in lung tissues, which could be induced by external agents such as metals. The manganese concentration in the lung tissue was 4.64 microg/g compared to 0.42-0.7 microg/g in the controls. The levels of other metals, such as iron, nickel, cobalt and zinc in patient's lung tissue were higher than those in the controls. The patient was probably exposed to Si and various metal dusts, and the lung fibrosis was related to these exposures. Exposure to Si and metal dusts should be sought in the history of any patient with SLE, especially in a male with pulmonary signs, and if present, exposure should be stopped. In the meantime, steps should be taken to ensure that workers exposure to Si and metal dusts in all environments have adequate protection.
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PMID:Pulmonary fibrosis in a steel mill worker. 1080 2

The study was undertaken to investigate the influence of alpha-tocopherol on zinc, copper, iron, calcium, magnesium, and potassium concentrations in serum of rats with bleomycin-induced pulmonary fibrosis. Fourteen Wistar albino rats were randomly divided into two groups of seven animals each. The first group was treated intratracheally with bleomycin hydrochloride (BM group); the second group was also instilled with BM but received injections of alpha-tocopherol twice a week (BM+E group). The third group was treated in the same manner with saline solution only, acting as controls (C). The zinc concentrations of the BM and BM+E groups were significantly decreased compared to the controls (p<0.05). The iron concentration of the controls was significantly higher than the other two groups. The magnesium concentration in the controls and the BM+E group was significantly higher than that of the BM group. The serum copper, calcium, and potassium concentrations were not found to be statistically different among the three groups. Distinct histopathologic changes were found in the BM group compared to the untreated rats. Less severe fibrotic lesions were also observed in the BM+E group. The results of this study show that lungs of rats treated with bleomycin were seriously damaged and that vitamin E seemed to counteract some of the damage, as indicated by differences in the serum concentrations of major elements.
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PMID:Effects of alpha-tocopherol on serum trace and major elements in rats with bleomycin-induced pulmonary fibrosis. 1720


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