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)

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

Total glutathione levels and the activity of enzymes associated with antioxidant protection in neonatal lung are increased in response to hyperoxia. Glutathione levels in developing rat lung decreased from 24 nmol/mg protein on day 19 of gestation to approximately 12 nmol/mg protein at birth. The initial decrease in glutathione may be due to emergence of other antioxidant systems. Newborn rats placed in 100% oxygen showed a rapid and sustained increase in total glutathione levels which was primarily due to an increase in reduced glutathione. Explants obtained from 16-wk gestation human fetal lung or from 17- to 18-day fetal rat lung also showed increased total and reduced glutathione when cultured in 95% oxygen, 5% CO2 as compared with explants cultured in room air. Type II cells isolated from neonatal rats maintained in oxygen for 6 days also showed glutathione levels twice those found in cells isolated from animals in room air. The activity of antioxidant enzymes (glucose-6-phosphate dehydrogenase, glutathione peroxidase, glutathione reductase) was increased in lungs of newborn rats exposed to 100% oxygen either at birth or 2 days of age. Antioxidant enzyme activity of lung explants cultured in 95% oxygen, 5% CO2 was also higher than in explants maintained in room air. These results suggest that the increases in glutathione and of antioxidant enzymes in vivo and in vitro are a direct effect of oxygen exposure in lung and that the increase of both glutathione and antioxidant enzyme activity is intrinsic to the lung cell itself. It is likely that increases in glutathione in lung represent an important protective mechanism against oxidant injury.
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PMID:The responses of glutathione and antioxidant enzymes to hyperoxia in developing lung. 403 84

Selenium ingestion may inhibit carcinogenesis. Epidemiologic studies have shown that age-adjusted death rates for cancer at most head and neck sites are lower in states where the soil and forage crops contain higher levels of selenium. The mode of action is incompletely understood, but may be mediated through an increase in the activity of the selenium dependent, antioxidant enzyme glutathione peroxidase (GSH-Px). The authors studied blood selenium levels and blood and tissue GSH-Px activities in 50 patients with untreated cancer of the oral cavity and oropharynx. Mean erythrocyte selenium and glutathione peroxidase were significantly depressed when compared to age-matched controls. Mean plasma selenium, on the other hand, was significantly elevated in the cancer patient group. Data from subsets within the cancer patient group were also discussed. GSH-Px activity did not differ in tumor and adjacent normal tissue. The concept of chemoprevention of carcinogenesis with inhibitory chemical compounds is particularly apropos to head and neck cancer control. Further work is indicated to determine if ingestion of supplemental selenium corrects the abnormalities identified here, and what affect, if any, this would have on the development and behavior of squamous cell cancers in the upper aerodigestive tract.
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PMID:Selenium and glutathione peroxidase levels in patients with epidermoid carcinoma of the oral cavity and oropharynx. 682 99

The 'antioxidant' enzymes superoxide dismutase (SD), catalase and glutathione peroxidase (GSH-Px) were found greatly elevated in red blood cells of subjects with beta-thalassaemia minor and similar to normal values in red blood cells of subjects with beta-thalassaemia major. These findings allows us to speculate that red cells in beta-thalassaemia minor react to the increased oxidant threat with augmented antioxidant enzyme activities. The normal levels of antioxidant enzymes in beta-thalassaemia major seem to be due to the presence of normal red cells owing to multiple transfusions.
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PMID:Erythrocyte superoxide dismutase, catalase and glutathione peroxidase activities in beta-thalassaemia (major and minor). 744 78

The dose and duration limiting toxic effects of cisplatin are ototoxicity and nephrotoxicity. While several studies have attempted to shed some light on the causes of nephrotoxicity, the reasons for ototoxicity induced by cisplatin are poorly understood. Therefore, this investigation was undertaken to delineate the potential mechanisms underlying cisplatin ototoxicity. The role of glutathione (GSH), oxidized glutathione (GSSG) and malondialdehyde levels, and antioxidant enzyme activities [superoxide dismutase, catalase, GSH peroxidase, and GSH reductase] were examined in cochlear toxicity following an acute dose of cisplatin. Male Wistar rats were treated with various doses of cisplatin. Pretreatment auditory brain stem evoked responses (ABR) were performed and then post-treatment ABRs and endocochlear potentials were also performed after three days. Acute cochlear toxicity (ototoxicity) was evidenced as elevated hearing thresholds and prolonged wave I latencies in response to various stimuli (clicks and tone bursts at 2, 8, 16 and 32 kHz) on ABRs. The endocochlear potentials were reduced (50% control) in cisplatin-treated rats as compared to control animals. The rats were sacrificed and cochleae isolated. The GSH, GSSG and malondialdehyde levels, and antioxidant enzyme activities were determined. Cisplatin ototoxicity correlated with a decrease in cochlear GSH [0.45 +/- 0.012 nmol/mg] after cisplatin administration compared to 0.95-012 nmol/mg in control cochleae (P < 0.05). Superoxide dismutase, catalase activities and malondialdehyde levels were significantly increased in the cochleae of cisplatin injected rats. Cochlear GSH-peroxidase and GSH reductase activity significantly decreased after cisplatin administration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanism of cisplatin ototoxicity: antioxidant system. 747 81

In this study, we examined the effects of oxidative stress adaptation on myocardial ischemic reperfusion injury. Oxidative stress was induced by injecting endotoxin (0.5 mg/kg) into the rat. After 24 h, rats were killed, hearts were isolated, and the effects of ischemia-reperfusion were studied using an isolated working heart preparation. The development of oxidative stress was examined by assessing malonaldehyde production in the heart. The antioxidant defense system was studied by estimating antioxidant enzyme activities and ascorbate- as well as thiol-dependent antioxidant reserve. The results of our study indicated that endotoxin induced oxidative stress within 1 h of treatment; the stress was reduced progressively and steadily up to 24 h. The antioxidant enzymes superoxide dismutase, catalase, glutathione (GSH) peroxidase, and GSH reductase were lowered up to 2 h and then increased. Both thiol- and ascorbate-dependent antioxidant reserve were enhanced, but the enhancement of the former was only transitory. After 24 h, endotoxin provided adequate protection to the heart from the ischemic-reperfusion injury, as evidenced by improved left ventricular function and aortic flow. Our results suggest that the induction of oxidative stress by endotoxin-induced adaptive modification of the antioxidant defense in the heart, thereby reducing ischemic-reperfusion injury.
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PMID:Myocardial adaptation to ischemia by oxidative stress induced by endotoxin. 748 60

The protective effect of melatonin on lipopolysaccharide (LPS)-induced oxidative damage in phenobarbital-treated rats was measured using the following parameters: changes in total glutathione (tGSH) concentration, levels of oxidized glutathione (GSSG), the activity of the antioxidant enzyme glutathione peroxidase (GSH-PX) in both brain and liver, and the content of cytochrome P450 reductase in liver. Melatonin was injected intraperitoneally (ip, 4mg/kg BW) every hour for 4 h after LPS administration; control animals received 4 injections of diluent. LPS was given (ip, 4 mg/kg) 6 h before the animals were killed. Prior to the LPS injection, animals were pretreated with phenobarbital (PB), a stimulator of cytochrome P450 reductase, at a dose 80 mg/kg BW ip for 3 consecutive days. One group of animals received LPS together with Nw-nitro-L-arginine methyl ester (L-NAME), a blocker of nitric oxide synthase (NOS) (for 4 days given in drinking water at a concentration of 50 mM). In liver, PB, in all groups, increased significantly both the concentration of tGSH and the activity of GSH-PX. When the animals were injected with LPS the levels of tGSH and GSSG were significantly higher compared with other groups while melatonin and L-NAME significantly enhanced tGSH when compared with that in the LPS-treated rats. Melatonin alone reduced GSSG levels and enhanced the activity of GSH-PX in LPS-treated animals. Additionally, LPS diminished the content of cytochrome P450 reductase with this effect being largely prevented by L-NAME administration. Melatonin did not change the content of P450 either in PB- or LPS-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Melatonin administration prevents lipopolysaccharide-induced oxidative damage in phenobarbital-treated animals. 759 65


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