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)

Hyperoxic adult rats have prolonged survival and reduced morphological evidence of lung injury when treated with a single dose of bacterial endotoxin; this effect is mediated by an augmentation of antioxidant enzyme activity in lung homogenate. To determine whether endotoxin would prolong survival and influence antioxidant enzyme levels in lambs whose physiological response to O2 breathing can be serially measured, we administered a single intravenous dose of endotoxin (0.75 microgram/kg body wt) to 13 lambs before exposing them to greater than 95% O2 (n = 11) or air (n = 2). Seven additional lambs were placed in O2 after receiving only saline vehicle. All lambs had been instrumented to measure pulmonary vascular pressures and cardiac output, and 10 lambs had lung lymph fistulas. O2-exposed control lambs developed noncardiogenic pulmonary edema and respiratory failure within 85 +/- 10 h (range 76-110 h); antioxidant enzymes were not increased, but reduced glutathione (GSH) levels fell and oxidized glutathione (GSSG) increased, reflecting the oxidant stress of O2 exposure. By contrast, endotoxin-treated O2-exposed lambs had a delayed increase in microvascular permeability to protein, a reduced rate of lung edema formation, normal gas exchange after 72 h in O2, and prolonged survival (136 +/- 15 h; range 90-160 h; all variables P less than 0.05). Despite prolonged survival, postmortem lung water content was no greater in the lambs that received endotoxin. Treatment with endotoxin did not increase antioxidant enzyme levels in lung homogenate, but levels of GSH relative to GSSG were significantly elevated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pulmonary O2 toxicity in lambs: physiological and biochemical effects of endotoxin infusion. 305 84

Oxygen free radicals have the potential to mediate cell injury. Defenses against such radicals include the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX). The purposes of this study were (1) to develop an in vitro model using human cells in which to investigate a potential pharmacologic agent as an inducer of these antioxidant enzymes; (2) to investigate the phenylurea derivative N-[2-(2-oxo-1-imidazolindinyl)ethyl]-N-phenylurea (EDU) in this model with paraquat (PQ) serving as the positive control; and (3) to determine if induction of the antioxidant enzymes by EDU occurs in vivo. Human gingival fibroblasts (Gin-1) were used as the target cell in vitro; PQ and EDU, an inducer of SOD and CAT activities in plants, were evaluated as antioxidant enzyme inducers. Total SOD activity in Gin-1 cells increased 2-fold (p less than 0.05) in the presence of 1.0 mM PQ for 18-48 hr compared with untreated controls. Gin-1 cells incubated with 0.25-2.0 mM PQ for 24 hr had significantly increased total SOD (1.5 to 2.0-fold; p less than 0.05). CAT activity increased with 1.0 and 2.0 mM PQ (p less than 0.05). In the presence of PQ, GSH-PX activity decreased (p less than 0.05) in a concentration-dependent manner, indicating inactivation of this enzyme. No toxicity, indicated by lactate dehydrogenase released into the incubation medium, was noted at PQ concentrations below 5.0 mM. In the presence of 0.125-2.0 mM EDU, total SOD activity in Gin-1 cells significantly increased (1.5 to 2.0-fold; p less than 0.05). CAT activity significantly increased in a dose-dependent manner (p less than 0.05), while GSH-PX activity remained constant following exposure to 0.125-2.0 mM EDU. Intraperitoneal administration of EDU to rats twice a day for 2 days at 100 mg/kg induced SOD activity in heart, liver, and lung compared to controls (p less than 0.05). CAT activity increased in the liver 56% and in the lung 36% (p less than 0.05). GSH-PX activity remained constant. Our findings indicate that Gin-1 cells are a useful model in which to study inducers of antioxidant enzymes in vitro and that the phenylurea compound EDU induces SOD and CAT activities both in vitro and in vivo.
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PMID:Induction of antioxidant enzyme activities by a phenylurea derivative, EDU. 318 24

Buthionine sulfoximine (BSO), an inhibitor of de novo synthesis of glutathione (GSH), was used to deplete rats of GSH and determine the effect of treatment on antioxidant enzyme responses, lung injury, and the susceptibility to concurrent sublethal or lethal hyperoxia. In a preliminary experiment, total lung nonprotein sulfhydryl (NPSH) and GSH levels were measured at various times after single doses of BSO. The lowest concentrations were observed at 12 to 18 h. These experiments were used to establish a repeated dosing protocol for more prolonged GSH depletion. The lungs of rats treated with BSO for 4 days demonstrated markedly decreased GSH and NPSH levels (10 to 40% of control values) and glutathione peroxidase activity (45 to 60% of control values). Superoxide dismutase activities were elevated, glutathione reductase activity was slightly elevated, and catalase activity was unchanged. These changes were dose-responsive. The lungs of treated rats were grossly and microscopically normal. BSO treatment of additional rats did not increase susceptibility to lethal hyperoxia (greater than 98% oxygen). Combined treatment of rats with both BSO and sublethal hyperoxia (80% oxygen) for 4 days did not alter the biochemical responses demonstrated by rats treated solely with BSO. The marked increase in catalase activity obtained after hyperoxia alone was not observed in rats treated with both hyperoxia and BSO. The lungs of saline- and BSO-treated rats exposed to sublethal hyperoxia demonstrated a patchy distribution of slight perivascular and peribronchiolar edema.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The pulmonary effects of buthionine sulfoximine treatment and glutathione depletion in rats. 320 1

Malarial parasites are believed to be more susceptible to oxidative stress than their hosts. BCNU(1,3-bis(2-chloroethyl)-1-nitrosourea) and HeCNU(1-(2-chloroethyl)-3-(2-hydroxythyl)-1-nitrosourea), inhibitors of the antioxidant enzyme glutathione reductase, were found to prevent the growth of Plasmodium falciparum in all intraerythrocytic stages. When exposing infected red blood cells to 38 microM BCNU or 62 microM HeCNU for one life cycle of synchronously growing parasites, the parasitemia decreased by 90%. During the formation of new ring forms, the parasites are even more susceptible to these drugs. The treatment with BCNU or HeCNU produced a rapid depletion of GSH in the parasites and their host cells; in addition, protection against lipid peroxidation was impaired in these cells. Possible mechanisms for the antimalarial action of the inhibitors are discussed. Our results suggest that erythrocyte glutathione reductase, an enzyme of known structure, might be considered as a target for the design of antimalarial drugs.
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PMID:Glutathione reductase inhibitors as potential antimalarial drugs. Effects of nitrosoureas on Plasmodium falciparum in vitro. 327 12

We investigated the possible involvement of reactive oxygen radical-related processes in chronic (12-wk) diabetes induced in rats by streptozocin (STZ). Diabetes was associated with significantly increased activities of catalase (CAT), glutathione reductase (GSSG-RD), and CuZn-superoxide dismutase (SOD) in the pancreas and of CAT and GSSG-RD in the heart. On the other hand, the liver of diabetic rats showed a generalized decrease in CAT, glutathione peroxidase (GSH-PX), and SOD as well as in the levels of reduced glutathione (GSH). Diabetic kidney also showed decreases in CAT and SOD, but the activities of GSH-PX were increased. Insulin treatment (9-12 U/kg body wt) that was started after 8 wk of diabetes and continued for 4 wk reversed all of the foregoing alterations in tissue antioxidant status. Our results suggest the presence of increased oxidative stress in uncontrolled diabetes as manifested by the marked alterations in tissue antioxidant enzyme activities, the magnitude of which increased with the degree of emaciation. The complex patterns of changes observed in the various tissues examined are believed to be the result of compensatory increases in enzyme activities (usually involving enzymes whose activity in control tissues is low) and direct inhibitory effects, possibly resulting from an increased tissue-oxidant activity. Our findings support the view that tissue antioxidant status may be an important factor in the etiology of diabetes and its complications.
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PMID:Alterations in free radical tissue-defense mechanisms in streptozocin-induced diabetes in rat. Effects of insulin treatment. 330 71

The effects of chronic intake of dietary alcohol upon left ventricular function, activities of myocardial antioxidant enzymes, reduced glutathione (GSH) content and lipoperoxidation (measured as the formation of diene conjugates and lipid-soluble fluorescence) were studied in adult domestic Nicholas turkeys. The non-invasive evaluation of left ventricular function by echocardiography revealed an impaired contractile function (the calculated fractional shortening values were 31.1 +/- 4.1% in the alcoholic group and 38.8 +/- 4.4% in the controls) and dilatation of the heart in the alcoholic birds. The changes in the non-invasive parameters of the left ventricle indicate that the adult Nicholas turkey developed congestive cardiomyopathy secondary to the ingestion of ethanol. In the hearts of normal adult turkeys, high GSH content (2.39 +/- 0.25 mumol/g wet weight) and superoxide dismutase activity were found, as compared to other animals, indicating the relatively higher development of antioxidant defence systems. Compared to the controls, significant increases were noted for all the antioxidant enzymes investigated (superoxide dismutase, catalase and glutathione peroxidase) and a moderately significant decrease in the GSH content was found in the left ventricle of alcoholic birds. The changes in GSH concentration and antioxidant enzyme activities might indirectly indicate some involvement of free radicals in the pathogenesis of ethanol-induced myocardial lesion. However, the levels of in vivo lipoperoxidation in the alcoholic birds did not significantly vary from those of control turkeys. Based on these findings, it appears that the reactive oxygen radicals may play a less important role in the pathogenesis of alcohol-induced cardiomyopathy in turkeys--probably due to the higher development of myocardial antioxidant defence systems.
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PMID:Alcohol-induced congestive cardiomyopathy in adult turkeys: effects on myocardial antioxidant defence systems. 343

To investigate the role of carcinogenic chemicals as a possible cause for oxidative damage, rats were treated with N-nitrosodimethylamine (NDMA) and various measures of lipid peroxidation were followed. As an indication of enhanced peroxidative processes in vivo, NMDA treatment produced rapidly an increase in the rate of ethane exhalation. A single i.p. or p.o. injection of 10 mg/kg b.w. elevated ethane exhalation by 13-14 fold; a single dose of 0.5 mg/kg of NDMA (the smallest dose tested) increased 5-fold the amount of ethane exhaled. Similarly, lipid peroxidation in the liver of NDMA-treated rats (measured by diene conjugation, chemiluminescence, the production of fluorescent and TBA-reactive material) was found to be increased rapidly showing a peak already 20 min after dosing. Simultaneously, NDMA-treatment slightly decreased antioxidant enzyme activities and GSH contents in the liver. In isolated rat hepatocytes the lucigenin-dependent chemiluminescence, as well as H2O2 release, were increased by micromolar concentrations of NDMA. Finally, it was shown that the rate of NADPH-stimulated ethane production by hepatic microsomes, prepared from untreated rats, was increased in the presence of NDMA. Thus, our results demonstrate that the alkylating NDMA can induce oxidative stress in rodents. Whether the same is true for other classes of carcinogens and processes known to affect tumor initiation/progression is presently under investigation.
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PMID:Lipid peroxidation induced by N-nitrosodimethylamine (NDMA) in rats in vivo and in isolated hepatocytes. 350 39

Exposure of several different animal models to O2-induced lung injury has revealed marked differences in sensitivity of various species to O2 damage. These differences may be due in part to variation of cellular antioxidant defenses. To characterize lung antioxidant enzyme activities in different species, we measured lung activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GSH S-trans) in rat, hamster, baboon, and human lung. Soluble lung fractions were also fractionated on Sephadex G-150-S columns and GSH-Px activity was measured using both cumene hydroperoxide and H2O2. This was done to evaluate non-Se-dependent GSH-Px activity in these lung samples. Human lung was obtained at surgery from patients undergoing lobectomy or pneumonectomy for localized lung tumors. SOD activity was similar for all four groups. GSH-Px activity was higher in rat lung than baboon or hamster lung. Lung CAT activity was variable with the highest activity present in the baboon which revealed a lung CAT activity 10 times higher than activity present in the rat. Lung GSH S-trans activities were higher in hamster, baboon, and human lung than in rat lung. Non-Se-dependent GSH-Px was present in rat lung but absent in hamster, baboon, and human lung. We conclude that the hamster was the best model of the animals studied for mimicking human lung antioxidant enzyme activities. Rat lung antioxidant enzyme activities were markedly different from any of the other species examined.
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PMID:Species variation in lung antioxidant enzyme activities. 365 19

Nitrogen dioxide (NO2), an environmental oxidant pollutant, is toxic to lung cells. We evaluated the changes in antioxidant enzyme activities in porcine pulmonary artery (PA) and aortic (AO) endothelial cells in monolayer cultures. Confluent PA or AO endothelial cells were exposed to 3 or 5 ppm NO2 or air (control) for 3-24 h and assayed for GSH-reductase (GSH-red), GSH-peroxidase (GSH-per), and glucose-6-phosphate dehydrogenase (G6PDH) activities as well as for intracellular GSH content. After 3, 6, or 12 h exposure to 3 or 5 ppm, GSH-red and G6PDH activities were not different from those of controls in both PA and AO endothelial cells. Exposure to 3 or 5 ppm NO2 for 24 h resulted in significant increases in GSH-red (P less than 0.05) and G6PDH (P less than 0.001) activities in both cell types. GSH-per activity and GSH content in NO2-exposed PA and AO endothelial cells were not different from those of controls, irrespective of NO2 concentration and exposure time. These results indicate that enzyme activities of G6PDH and GSH-red are increased in PA and AO endothelial cells exposed to NO2, and this response is comparable, in part, to that in the lungs from animals exposed to NO2.
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PMID:Effect of NO2 exposure on antioxidant defense of endothelial cells. 377 82

We compared the effects of 95% O2 (hyperoxia) alone, endotoxin (20 ng/ml) alone, and 95% O2 plus endotoxin on the release of lactate dehydrogenase (LDH), uptake of 5-hydroxytryptamine (5-HT), and antioxidant enzyme activities in porcine pulmonary arterial and aortic endothelial cells in monolayer culture. Hyperoxia increased LDH release and decreased 5-HT in both endothelial cell types. Hyperoxia also caused a decrease in catalase (CAT) activity and an increase in total superoxide dismutase (SOD) and glutathione reductase (GSH-Red) activities in both cell types. Endotoxin alone had no effect on LDH release, 5-HT uptake, or antioxidant enzyme activities. However, endotoxin prevented the hyperoxic increase in LDH release and the hyperoxic decrease in 5-HT uptake. Endotoxin plus 95% O2 had no consistent effect on the antioxidant enzyme profile in pulmonary artery or aortic endothelial cells. These results indicate that (1) hyperoxia injures both pulmonary artery and aortic endothelial cells in culture and causes changes in the antioxidant enzyme profile that are similar in the two cell types; (2) hyperoxia-induced decreases in CAT activity and increases in SOD activity may be responsible for increased sensitivity of endothelial cells to O2 toxicity; and (3) endotoxin protects against hyperoxic injury to endothelial cells in vitro, but increases in antioxidant enzyme activities are not the mechanism for this protection.
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PMID:Effect of oxygen and endotoxin on lactate dehydrogenase release, 5-hydroxytryptamine uptake, and antioxidant enzyme activities in endothelial cells. 388 60


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