Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although the evidence for oxidative stress for air pollution in the human lung is fragmentary, the hypothesis that oxidative stress is an important, if not the sole, mechanism of toxicity of oxidizing air pollutants and tobacco smoke is compelling and growing. First, biochemical mechanisms have been worked out for oxidation of lung lipids by the gas phase of cigarette smoke, NO2 and O3. The oxidation of lung lipids can be prevented by both vitamins C and E. Vitamin C is more effective in preventing oxidation by NO2, and vitamin E is more effective against O3. Second, multiple species of experimental animals develop lung disease similar to human bronchitis and emphysema from exposure to NO2 and O3, respectively. The development of these diseases occurs over a near lifetime exposure when the levels of NO2 or O3 are at near ambient air pollution values. Third, isolated human cells are protected against oxidative damage from NO2 and O3 by both vitamins C and E. Fourth, the vitamin C level in the lung either declines on exposure to NO2 for short-term exposures or increases on chronic cigarette smoke exposure. The effects of cigarette smoking on serum vitamin C is apparently complex and may be related to the daily intake of vitamin C as well as smoking. Serum vitamin C levels may be poor indicators of lung demands when daily vitamin C intakes are above 100 mg/day. Fifth, vitamin C supplementation protects against the effects of ambient levels of air pollution in adults as measured by histamine challenge. An augmented response to histamine challenge may represent increased lung permeability brought about by air pollution. In experimental animal and human experiments, the amount of vitamin C or E that afforded protection was in excess of the current recommended dietary allowance. Although animal studies do not provide evidence for complete protection against NO2 or O3, they do illustrate that current recommended daily allowances are inadequate for maximum protection against air pollution levels to which over 100 million Americans are exposed. The problem of air pollution and its effects on humans is truly of global concern. Air pollution is not restricted to North America or Japan where it was first recognized, but is a major public health problem in Europe as well. When data are available, air pollution probably will be shown to be a major public health problem in all urban areas of the world.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Antioxidant vitamins and prevention of lung disease. 144 20

The effects of vitamin E deficiency on bleomycin (BLM)-induced pulmonary fibrosis have been studied by analyses of pressure volume (PV) curves and morphological examinations. Golden hamsters were divided into groups on a control diet (group C), vitamin E-deficient diet (E), control diet with BLM treatment (CB), and vitamin E-deficient diet with BLM treatment (EB). Group EB showed PV curves shifted downward and to the right soon after BLM administration (10 days) and gradually shifted upward and to the left compared to group CB in the later period (30 and 60 days after BLM treatment). Histologically group EB was characterized by relatively severe interstitial pneumonitis in the early stages. In later stages, emphysematous changes were induced in combination with a lesser degree of fibrosis in group EB. Mean thickness of the alveolar wall of group CB was larger than group C while that of group EB was smaller at 30 days after BLM treatment. These results indicate that, with BLM treatment, vitamin E-deficient hamsters show increased distensibility on the PV curve and emphysematous changes mixed with focal fibrosis on morphological examination. This means that by adding other modulating factors, such as vitamin E deficiency, BLM, an agent known to produce pulmonary fibrosis, acts to induce an emphysematous lesion in the lung. Although pulmonary fibrosis and emphysema have been considered to be final and different forms of parenchymal injury, each may proceed to the other under the influence of some modulating factors.
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PMID:Effects of vitamin E deficiency on bleomycin-induced pulmonary fibrosis in the hamster. 245 80

Lung inflammatory cells in idiopathic pulmonary fibrosis (IPF) is characterized by an increased spontaneous production of oxidants. This suggests that the oxidants may play a role in causing the epithelial cell injury in the early stage of IPF. Bleomycin (BLM) induces pulmonary fibrosis by oxidant production. We tested the hypothesis that a dietary supplement of vitamin E (VE) may protect against, and its deficiency may exacerbate, BLM-induced pulmonary fibrosis. Because the hamster is known to be the best model among animals studied mimicking human lung antioxidant enzyme activities, Syrian Golden hamsters were used in this study. In dietary VE supplement and BLM treated group (Ead.B), mean serum VE concentration increased by about 3 times that of control (C) and the BLM treated group (CB). Despite the remarkably high VE content, no significant difference was found between CB and Ead.B for pressure-volume (PV) curves and morphological data. In BLM treated with dietary VE deficient group (Ede.B), serum VE concentrations markedly decreased on all experimental days compared with other groups. Mechanical properties in P-V curves of Ede.B showed most less distensible characteristics in early stage and most distensible characteristics in later stage. These emphysematous changes observed in P-V curves in the later stage of Ede.B, coincided with the morphological observations. In the early stage of BLM treatment, lipid peroxide concentrations in the lung tissue were significantly higher in Ede.B compared with other groups. It was concluded that a dietary supplement of VE cannot protect against BLM-induced pulmonary fibrosis, and a dietary VE deficiency exacerbates BLM lung injury to produce on emphysema in the hamster.
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PMID:[Pulmonary fibrosis and antioxidant agents]. 247 76

The major cause of death in paraquat poisoning is a rapidly progressive respiratory failure due to an oxidative insult to the alveolar epithelium with subsequent fulminant obliterating fibrosis. The present study evaluates the effectiveness of vitamin E in combination with colchicine in ameliorating paraquat lung injuries in rats. Vitamin E is a biologic antioxidant interfering with lipid peroxidation, and colchicine reduces collagen synthesis which is significantly augmented in pulmonary fibrosis. Eight normal rats were given a single i.p. dose of paraquat at 15 mg/kg. The treated group included eight animals that received, in addition to i.p. paraquat (15 mg/kg), daily doses of vitamin E (100 mg/kg i.p.) and colchicine (0.1 mg/kg i.p.). All the rats in the paraquat group died within 42 to 96 h, six of them within 60 h, following severe respiratory failure. The treated rats developed a somewhat milder form of respiratory insufficiency, six of them dying within 48 to 72 h. Less severe intra-alveolar hemorrhages were observed in this group. Two rats survived, and these had only mild emphysema on autopsy at 21 days. Our preliminary results suggest that the combination of vitamin E with colchicine may be effective in ameliorating lung injuries caused by paraquat, and warrant further studies.
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PMID:Effectiveness of vitamin E and colchicine in amelioration of paraquat lung injuries using an experimental model. 270 31

3-Methylindole (3-MI) is a metabolite of tryptophan which causes acute pulmonary edema and emphysema in ruminants when administered orally or intravenously. 3-MI is metabolized by mixed-function oxidases to a reactive intermediate which may play a role in 3-MI-induced pneumotoxicity. Electron spin-trapping techniques have been used to investigate the in vitro and in vivo formation of free radicals during 3-MI metabolism by goat lung. A nitrogen-centered free radical of 3-MI has been generated from 3-MI in goat lung microsomal incubations. Although a nitrogen-centered free radical can be generated chemically from most of the indolic compounds, only the 3-MI free radical can be generated enzymatically. The formation of the nitrogen-centered 3-MI free radical was followed by the appearance of a carbon-centered lipid radical in microsomal preparations. The findings that an identical carbon-centered free radical was generated by FeSo4 in the microsomal system in the absence of 3-MI and that malonaldehyde formation is stimulated by 3-MI in microsomes led to the conclusion that 3-MI metabolism induces lipid peroxidation of microsomal membranes. The formation of 3-MI-induced lipid radicals was inhibited by vitamin E and glutathione. A carbon-centered radical was spin trapped in vivo in the lungs of goats infused with 3-MI. This radical had the same splitting constants as the carbon-centered lipid radical trapped in microsomal incubations containing 3-MI. This finding indicates that the metabolism of 3-MI in goat lung in vivo generates a lipid radical.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Involvement of free radicals in the mechanism of 3-methylindole-induced pulmonary toxicity: an example of metabolic activation in chemically induced lung disease. 300 1

Highly reactive molecules called free radicals can cause tissue damage by reacting with polyunsaturated fatty acids in cellular membranes, nucleotides in DNA, and critical sulfhydryl bonds in proteins. Free radicals can originate endogenously from normal metabolic reactions or exogenously as components of tobacco smoke and air pollutants and indirectly through the metabolism of certain solvents, drugs, and pesticides as well as through exposure to radiation. There is some evidence that free radical damage contributes to the etiology of many chronic health problems such as emphysema, cardiovascular and inflammatory diseases, cataracts, and cancer. Defenses against free radical damage include tocopherol (vitamin E), ascorbic acid (vitamin C), beta-carotene, glutathione, uric acid, bilirubin, and several metalloenzymes including glutathione peroxidase (selenium), catalase (iron), and superoxide dismutase (copper, zinc, manganese) and proteins such as ceruloplasmin (copper). The extent of tissue damage is the result of the balance between the free radicals generated and the antioxidant protective defense system. Several dietary micronutrients contribute greatly to the protective system. Based on the growing interest in free radical biology and the lack of effective therapies for many of the chronic diseases, the usefulness of essential, safe nutrients in protecting against the adverse effects of oxidative injury warrants further study.
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PMID:Free radical tissue damage: protective role of antioxidant nutrients. 331 7

Cigarette smoking produces oxidant-mediated changes in the lung important to the pathogenesis of emphysema. Since vitamin E can neutralize reactive oxygen species and prevent peroxidation of unsaturated lipids, it may constitute an important component of the lung's defense against oxidant injury. To better characterize the antioxidant protective role of vitamin E, young asymptomatic smokers and nonsmokers were evaluated by bronchoalveolar lavage before and immediately after a 3-wk course of oral vitamin E (2,400 IU/d). Smoker alveolar fluid at baseline was relatively deficient in vitamin E compared with nonsmoker fluid (3.1 +/- 0.7 ng/ml vs. 20.7 +/- 2.4 ng/ml, P less than 0.005). Although smoker alveolar fluid vitamin E levels increased to 9.3 +/- 2.3 ng/ml after supplementation, the levels remained significantly lower than nonsmoker baseline levels (P less than 0.01). This deficiency was explained, in part, by the increased oxidative metabolism of vitamin E to the quinone form in the lungs of smokers compared with nonsmokers. Although the significance of a lower concentration of alveolar fluid vitamin E is unclear, it may compromise the antioxidant protection afforded by the alveolar fluid as it coats the lung's epithelial surface. The protective role of vitamin E was assessed by cytotoxicity experiments, which demonstrated that the killing of normal rat lung parenchymal cells by smoker alveolar macrophages was inversely related to the vitamin E content of the parenchymal cells. These findings suggest that vitamin E may be an important lower respiratory tract antioxidant, and that the deficiency seen in young smokers may predispose them to an enhanced oxidant attack on their lung parenchymal cells.
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PMID:Deficiency of vitamin E in the alveolar fluid of cigarette smokers. Influence on alveolar macrophage cytotoxicity. 394 77

A common feature of cigarette-smoke (CS)-associated diseases such as atherosclerosis and pulmonary emphysema is the activation, aggregation, and adhesion of leukocytes to micro- and macrovascular endothelium. A previous study, using a skinfold chamber model for intravital fluorescence microscopy in awake hamsters, has shown that exposure of hamsters to the smoke generated by one research cigarette elicits the adhesion of fluorescently labeled leukocytes to the endothelium of arterioles and small venules. By the combined use of intravital microscopy and scanning electron microscopy, we now demonstrate in the same animal model that (i) CS-induced leukocyte adhesion is not confined to the microcirculation, but that leukocytes also adhere singly and in clusters to the aortic endothelium; (ii) CS induces the formation in the bloodstream of aggregates between leukocytes and platelets; and (iii) CS-induced leukocyte adhesion to micro- and macrovascular endothelium and leukocyte-platelet aggregate formation are almost entirely prevented by dietary or intravenous pretreatment with the water-soluble antioxidant vitamin C (venules, 21.4 +/- 11.0 vs. 149.6 +/- 38.7 leukocytes per mm2, P < 0.01; arterioles, 8.5 +/- 4.2 vs. 54.3 +/- 21.6 leukocytes per mm2, P < 0.01; aortas, 0.8 +/- 0.4 vs. 12.4 +/- 5.6 leukocytes per mm2, P < 0.01; means +/- SD of n = 7 animals, 15 min after CS exposure). No inhibitory effect was observed by pretreatment of the animals with the lipid-soluble antioxidants vitamin E or probucol. The protective effects of vitamin C on CS-induced leukocyte adhesion and aggregation were seen at vitamin C plasma levels (55.6 +/- 22.2 microM, n = 7) that can easily be reached in humans by dietary means or supplementation, suggesting that vitamin C effectively contributes to protection from CS-associated cardiovascular and pulmonary diseases in humans.
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PMID:Vitamin C prevents cigarette smoke-induced leukocyte aggregation and adhesion to endothelium in vivo. 751 84

Tobacco smoke is associated with pulmonary emphysema via elastase-antielastase and oxidant-antioxidant imbalance. This study addressed the tobacco smoke-induced changes in the lungs of weanling rats with vitamin E depletion. Three-week-old Wistar rats fed on vitamin E-depleted or normal diet were intermittently exposed to tobacco smoke by Hamburg II machines for 4 weeks. Tobacco smoke significantly suppressed body weight increases, particularly in the vitamin E-depleted group. In the normal diet group, tobacco smoke induced emphysematous changes with significant increases in the mean linear intercept (Lm) and the destructive index (DI), which was supported by an increase in elastase-like activity and a decrease in elastase inhibitory capacity (EIC) in bronchoalveolar lavage (BAL) fluid. Vitamin E depletion alone altered neither Lm nor DI. In tobacco-exposed animals in addition to vitamin E depletion, elastase-like activity, EIC in BAL fluid and DI were comparable to that in tobacco-exposed animals on a normal diet. However, Lm was markedly decreased with thickened epithelium and shrunk alveolar space. These results suggest that vitamin E depletion, when linked to tobacco exposure, might induce impaired lung development in the weanling rats, which is different from the emphysematous changes.
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PMID:Influences of tobacco smoke and vitamin E depletion on the distal lung of weanling rats. 758 48

This study confirms the fact that in different respiratory disorders, the status of plasma oxidants and antioxidants shifts from normal. The status of oxidants in plasma as represented by malondialdehyde (MDA) levels increased significantly in the conditions of chronic obstructive pulmonary disease (COPD), emphysema, bronchiectasis and bronchial asthma. The two vitamin antioxidants vitamin C and vitamin E showed decreased levels than in controls. In patients with COPD the endogenous antioxidant viz. reduced glutathione (GSH) estimated from whole blood was comparable to that of control group, whereas in patients with emphysema, bronchiectasis and bronchial asthma, GSH concentration was increased to that of control group. The activity of enzyme superoxide dismutase (SOD) was significantly decreased in all study groups. Pulmonary function tests were found to have no correlation with MDA and antioxidants.
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PMID:Plasma oxidant-antioxidant status in different respiratory disorders. 2310 36


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