Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Small dosages of endotoxin (100--500 micrograms/kg) provide significant protection against the acute manifestations of pulmonary O2 toxicity and lethality. Ninety-seven percent of endotoxin-treated adult rats survived a 72-h exposure to greater than or equal to 95% O2 with mimimal lung changes, compared to 32% of control animals (P less than 0.01). Exposure to greater than or equal to 95% O2 for 7 days resulted in a 20% survival rate in untreated control rats vs. 98% survival in endotoxin-treated rats (P LESS THan 0.01). Histological evaluation of lung from survivors revealed substantially less collagen and reticular fiber deposition in the endotoxin-treated animal lungs. Endotoxin treatment was associated with increased activity of the protectant antioxidant enzyme systems of the lung in an apparent dose-response manner. Endotoxin's protective activity against O2 toxicity does not appear to depend on an initial toxic insult to the lung like with alpha-naphthylthiourea, oleic acid, or alloxan treatment. The data support a protective role for endotoxin against the acute and the more chronic manifestations of O2-induced pulmonary injury.
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PMID:Endotoxin protection against oxygen-induced acute and chronic lung injury. 53 52

Asbestos resembles the phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA), in its ability to elicit release of superoxide (O2-.) from rodent alveolar macrophages (AM) in vitro. In addition, superoxide dismutase (SOD), the antioxidant enzyme scavenging O2-, is increased in cultures of tracheobronchial epithelial cells and lung fibroblasts after exposure to either crocidolite or chrysotile asbestos. Our objectives here were to determine: (1) the chemical and physical properties of asbestos important in the generation of O2- from rat AM; and (2) the effects of O2- in comparison with asbestos on biosyntheses of collagen and non-collagen protein in rat lung fibroblasts in vitro. We were also interested in whether increased production of SOD occurred in the lungs of rats after inhalation of crocidolite asbestos. To determine whether O2- was elicited in response to a variety of asbestiform fibres, AM lavaged from Fischer 344 rat lungs were exposed in vitro to equivalent non-toxic amounts of crocidolite asbestos, erionite, Code 100 fibreglass, sepiolite, and their non-fibrous analogues, riebeckite, mordenite and glass particles. In addition, sized preparations of long (greater than 10 microns) and short (less than 2 microns) asbestos were introduced at identical concentrations to determine whether length of fibres is critical in O2- release. The amount of O2- released from AM in response to dusts was then determined by measuring SOD-inhibitable reduction of cytochrome C. All asbestiform fibres caused a significant (p less than 0.05) increase in generation of O2- from epithelial cells, whereas non-fibrous particles were less active at comparable concentrations. Experiments with long (greater than 10 microns) versus short (less than 2 microns) chrysotile showed that long fibres caused a more striking, dosage-dependent release of O2-. To determine whether O2- plays a role in the causation of fibrotic lung disease, rat lung fibroblasts were exposed to a biochemical generation system (xanthine-xanthine oxidase) for O2- before quantitation of cell-associated collagen and non-collagen protein at 24, 48 and 72 h thereafter. At the latter time periods, significant increases in total collagen per ng DNA were observed. In comparison with controls, the generation system for O2- also caused an initial decrease in synthesis of non-collagen protein followed by increases in synthesis of non-collagen protein at 48 and 72 h.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mechanisms of fibre-induced superoxide release from alveolar macrophages and induction of superoxide dismutase in the lungs of rats inhaling crocidolite. 254 20

Variations in superoxide dismutase, catalase and glutathione peroxidase activity were studied in fibroblasts cultured in the presence of hydralazine, a drug known to be an inducer of the so-called collagen-like syndrome. The results demonstrated that both superoxide dismutase and catalase undergo a marked decrease in their activity, whereas glutathione peroxidase manifests a significant increase in its activity after treatment with hydralazine as compared to control cell cultures. Also the lipid peroxide concentration as expressed by the malondialdehyde amount was estimated in the above cultures. The altered antioxidant enzyme activity and the presence of byproducts of free radical damage support the possibility that the action of hydralazine leading to the pathogenesis of collagen disease-like syndrome involves an abnormal free-radical metabolism.
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PMID:Activities of antioxidant enzymes in fibroblasts cultured in vitro in the presence of hydralazine. 261 21

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

Hyperplastic nodular cirrhosis was induced in rats by long-term (6 month) i.p. administration of thioacetamide at doses of 2.66 mmol/kg body wt, three times per week. The survival rate of animals at the end of the treatment was 90%. To follow the temporal changes samples at 0, 7, 15, 30, 45, 60, 90, 150 and 180 days from rats during thioacetamide intoxication and from chronological controls were obtained. The cirrhogenic ability of this treatment was assessed on the basis of morphological changes: the development of macronodular cirrhosis and the appearance of fibrous septa of collagen through portal spaces. Parameters of liver injury and cholestasis were obtained by assaying the serum activities of isocitrate dehydrogenase and gamma-glutamyltransferase. Enzymes and metabolites related to glutathione redox systems, as well as other antioxidant enzymes, were tested. Catalase and glutathione peroxidase, the two enzymes involved in the elimination of peroxides, and glutathione reductase decreased significantly at the end of the 6 months of intoxication, while Cu-Zn and Mn superoxide dismutases increased progressively during the long-term thioacetamide treatment. Protein thiol levels profile showed a biphasic change increasing from the 7th day and were insensitive to the 30% depletion of intracellular glutathione (GSH). To study the relationship of the intracellular thiols on the mechanisms of cell proliferation and differentiation during the cirrhogenic process, DNA content was assayed by flow cytometry in isolated hepatocytes, and DNA ploidy and distribution between G0-G1, S and G2 + M phases were determined. Remarkable changes in relation to a sharp increase in diploid population from 7 to 180 days (24.5%-->85.5%), a pronounced decrease in polyploid populations (tetraploid+octoploid) in the same period (73.7%-->12.3%), and elevations in the populations in S phase (S1 + S2) were observed in thioacetamide-treated rats. The results obtained indicate that hepatocytes isolated from thioacetamide-treated rats showed a marked tendency to diploidy, an enhancement in DNA replication parallel to the hepatic content of protein sulphydryl groups and a significant decline in antioxidant enzyme activities. The increase in protein thiols was independent of GSH level and of the thiol redox state.
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PMID:Relationship between antioxidant systems, intracellular thiols and DNA ploidy in liver of rats during experimental cirrhogenesis. 761 93

To clarify the role of catalase, an antioxidant enzyme, in response to UV irradiation, we compared the effects of irradiation on cytotoxicity, activities of antioxidant enzymes, total glutathione concentrations, lipid peroxidation and the rate of collagen synthesis in skin fibroblasts from a patient with acatalasaemia and in those from a normal individual. The cells were irradiated with UVA (6 and 12 J/cm2 or UVB (0.5 and 1 J/cm2). Cell survival curves after UV irradiation were similar in cells from both subjects. Although superoxide dismutase activity in acatalasaemia cells was higher than in the control cells before irradiation, after irradiation the activity decreased in acatalasaemia cells (76% with 12 J/cm2 UVA, 47% with 1 J/cm2 UVB), but remained unchanged in control cells. Total glutathione concentrations also decreased in acatalasaemia cells (60% with 12 J/cm2) in response to UVA irradiation, but remained unchanged in control cells. Lipid peroxidation did not increase significantly in either cell type. The rate of collagen synthesis decreased to a similar extent in response to UV exposure in the two cell types (60-80% with 8.2 J/cm2 UVA, 40-50% with 10 mJ/cm2 UVB). We conclude from the results of cytotoxicity and lipid peroxidation that although acatalasaemia cells were killed by hydrogen peroxide at low concentrations with a single UV exposure, catalase functions only to a small degree as an antioxidant enzyme. There remains the possibility, however, that a deficiency of catalase may chronically damage the skin resulting in a reduced defence function of superoxide dismutase and glutathione with repeated exposures to UV, which is becoming more common in our daily life.
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PMID:Antioxidant defence mechanism of the skin against UV irradiation: study of the role of catalase using acatalasaemia fibroblasts. 855 87

The present study was designed to investigate and compare the effects of dietary selenium (Se) and vitamin E on some physiological parameters and histological changes in liver, heart, and skin tissues, as well as the blood parameters and the related enzymes. Both sex young rabbits were fed with deficient (9.8 micrograms/kg diet), adequate (225 micrograms/kg diet), and rich (4.2 mg/kg diet) Se and vitamin E diets for 12-15 wk for this purpose. As the plasma Se levels and the erythrocyte glutathione (GSH) peroxidase activity decreased (79.8 +/- 9.4 ng/mL and 2.0 +/- 0.3 U/g Hb, respectively) in the deficient group, these values increased (100.4 +/- 2.7 ng/mL and 14.5 +/- 4.3 U/g Hb) in the rich group significantly with respect to the control group. The other antioxidant enzyme activities and the related element levels did not change significantly in either one of the experimental groups. Although the platelet counts of the two experimental groups were not different from the control values, the collagen and the adenosine diphosphate (ADP) stimulated platelet aggregation rate and intensity increased in the deficient group (p < 0.05) and decreased very significantly (p < 0.001) in the rich group. In both of the experimental groups, as the percentage values of the neutrophils decreased, the lymphocytes and the eosinophils increased significantly. According to the light microscopic investigations, the observed lesions of considerable intensity within the tissues that elicit cell degenerations were more pronounced in the animals fed with the rich diet than in those fed with the deficient diet. The deficiency as well as toxicity of Se and the deficiency of vitamin E caused several alterations in the physiological functions of the tissues, and these alterations were supported by the histological lesions within these tissues.
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PMID:Dietary selenium- and vitamin E-induced alterations in some rabbit tissues. 940 35

Oxidative stress is involved in both the pathogenesis and complications of diabetes. ACE inhibitors can slow the progression of cardiac and renal impairments related to diabetes. The effect of enalapril treatment on oxidative stress and tissue injury was studied in hearts, kidneys, and livers from streptozotocin-induced diabetic rats. Twenty-four rats were divided into the following groups: streptozotocin (65 mg/kg, single intraperitoneal dose), streptozotocin+enalapril (20 mg enalapril/L drinking water), and control (intraperitoneal saline). Seven months after streptozotocin injection, organs were studied by light microscopy and collagen III immunolabeling. Tissue lesions and collagen labeling were graded by a semiquantitative score (0 to 4). Total glutathione content, glutathione redox status (reduced/oxidized glutathione), antioxidant enzyme activities, protein-associated sulfhydryls, thiobarbituric acid-reactive substances, and fluorescent chromolipids were determined in tissue homogenates. Glycemia was higher in both the streptozotocin and streptozotocin+enalapril groups relative to the control group. In the streptozotocin group, creatinine clearance and body weight were lower, and systolic blood pressure and urinary albumin excretion were higher than in the streptozotocin+enalapril and control groups. Heart, kidney, and liver lesion/labeling scores were significantly higher in the streptozotocin group compared with the streptozotocin+enalapril and control groups. Kidney and liver total glutathione was lower in the streptozotocin group relative to the control group (P<0.05). Enalapril treatment significantly attenuated the reduction of total glutathione. In the heart, kidney, and liver, both glutathione and proteins were relatively more oxidized in the streptozotocin group relative to the control group (P<0.05). Protein and glutathione oxidation were attenuated in the streptozotocin+enalapril group in the 3 tissues studied (P<0.05). Enalapril treatment attenuated the oxidation of lipids in the heart and kidney (P<0.05). Tissue fibrosis scores were inversely correlated with (1) both total glutathione and reduced/oxidized glutathione in heart, kidney, and liver and (2) glutathione reductase activity in the kidney. These results suggest that in streptozotocin-induced diabetic rats, the protective action of enalapril might be mediated, at least in part, by its effect on tissue oxidant/antioxidant status.
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PMID:Enalapril attenuates oxidative stress in diabetic rats. 1171 10

The mechanism of cadmium-mediated hepatotoxicity has been the subject of numerous investigations, principally in hepatocytes. Although, some uncertainties persist, sufficient evidence has emerged to provide a reasonable account of the toxic process in parenchymal cells. However, there is no information about the effect of cadmium in other hepatic cell types, such as stellate cells (fat storing cells, Ito cells, perisinusoidal cells, parasinusoidal cells, lipocytes). Hepatic stellate cells (HSC) express a quiescent phenotype in a healthy liver and acquire an activated phenotype in liver injury. These cells play an important role in the fibrogenic process. The objective of this study was to investigate the effect of a 24 h treatment of low Cd concentrations in glutathione content, lipid peroxidation damage, cytosolic free Ca, antioxidant enzyme activities: glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase along with the capacity of this heavy metal to induce metallothionein II and alpha(1)collagen (I) in an hepatic stellate cell line (CFSC-2G). Cd-treated cells increased lipid peroxidation and the content of cytosolic free calcium, decreased glutathione content and superoxide dismutase, glutathione peroxidase and catalase activity. Cd was able to induce the expression of the metallothionein II and alpha(1)collagen (I) gene, that was not described in this cell type. Cadmium may act as a pro-fibrogenic agent in the liver probably by inducing oxidative damage by enhancing lipid peroxidation and altering the antioxidant system of the cells. Although, the exact role metallothionein induction plays in this process is unknown, it probably, provides a cytosolic pool of potential binding sites to sequester ionic Cd, thereby decreasing its toxicity.
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PMID:Cadmium induces alpha(1)collagen (I) and metallothionein II gene and alters the antioxidant system in rat hepatic stellate cells. 1175 84

Bleomycin administration results in well-described intracellular oxidative stress that can lead to pulmonary fibrosis. The role of alveolar interstitial antioxidants in this model is unknown. Extracellular superoxide dismutase (EC-SOD) is the primary endogenous extracellular antioxidant enzyme and is abundant in the lung. We hypothesized that EC-SOD plays an important role in attenuating bleomycin-induced lung injury. Two weeks after intratracheal bleomycin administration, we found that wild-type mice induced a 106 +/- 25% increase in lung EC-SOD. Immunohistochemical staining revealed that a large increase in EC-SOD occurred in injured lung. Using mice that overexpress EC-SOD specifically in the lung, we found a 53 +/- 14% reduction in bleomycin-induced lung injury assessed histologically and a 17 +/- 6% reduction in lung collagen content 2 wk after bleomycin administration. We conclude that EC-SOD plays an important role in reducing the magnitude of lung injury from extracellular free radicals after bleomycin administration.
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PMID:Role of extracellular superoxide dismutase in bleomycin-induced pulmonary fibrosis. 1188 Feb 97


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