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)

Selenium is a trace element which plays a vital role in many metabolic functions and in particular is an integral part of the antioxidant enzyme glutathione peroxidase. It may be involved in the prevention of a number of diseases including cardiovascular diseases and cancer, which are the main causes of death in Singapore with ethnic differences. The National University of Singapore Heart Study measured cardiovascular risk factors, including serum selenium, in a random of the general population aged 30 to 69 years from 1993 to 1995. Mean serum selenium was higher in Chinese (males 126 and females 119 micrograms/L) and Malays (males 122 and females 122 micrograms/L) than Indians (males 117 and females 115 micrograms/L). These levels (with an estimated mean of 122 micrograms/L in Singapore) are lower than those in the USA but higher than those in Western Europe. The proportions with serum selenium < 80 micrograms/L (classified as low values) were low, though highest in Indians (males 1.2% and females 1.2%), then Chinese (males 0.6% and females 1.3%) and then Malays (males 0.0% and females 0.0%), but the differences were not statistically significant. The overall estimate for the prevalence of low selenium in Singapore was 0.8%. It is concluded that levels of serum selenium in Singapore are satisfactory and no action with regard to dietary supplementation is needed. Serum selenium levels are slightly lower in Indians than in Chinese and Malays (probably due to a more vegetarian diet) and this may make a small contribution to Indians' higher rates of coronary heart disease compared to Chinese and Malays.
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PMID:Serum selenium in the general population of Singapore, 1993 to 1995. 979 58

Environmental tobacco smoke (ETS) is a pervasive contaminant in the workplace. Previous studies by this laboratory have shown that exposure to workplace ETS results in increased oxidative stress and damage, as measured by increased levels of the antioxidant enzymes superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase. 8-Hydroxy-2-deoxyguanosine, a marker of oxidative DNA damage, was also 63% greater in the exposed group compared with controls. Subjects in the previous study who reported workplace exposure to ETS were given a 60-day supply of an over-the-counter antioxidant formulation consisting of 3000 microg of beta-carotene, 60 mg of vitamin C, 30 I.U. of alpha-tocopherol, 40 mg of zinc, 40 microg of selenium, and 2 mg of copper. After the 60-day supplementation period, blood samples were again drawn, and the results were compared with the presupplementation values. A 62% decrease in 8-hydroxy-2-deoxyguanosine was observed after supplementation. Lipid peroxidation levels were also decreased, as were the antioxidant enzyme activities. The biochemical evidence suggests that exposure to ETS in the workplace increases oxidative stress and that antioxidant supplementation may provide some protection.
Cancer Epidemiol Biomarkers Prev 1998 Nov
PMID:Oxidative stress induced by environmental tobacco smoke in the workplace is mitigated by antioxidant supplementation. 982 5

The cancer chemopreventive effect of selenium cannot be fully accounted for by the role of selenium as a component of the antioxidant enzyme glutathione peroxidase, which suggests that chemoprevention occurs by another mechanism. Several studies have shown that thiol oxidation and free radical generation occur as a consequence of selenium catalysis and toxicity. In the present study, we evaluated three different selenium compounds; selenite, selenocystamine, and selenomethionine to determine the relative importance of the prooxidative effects of these compounds with regard to their ability to induce apoptosis. The experimental results suggest that, in addition to supporting an increased activity of glutathione peroxidase, an antioxidant function that the three selenium compounds did with equal efficacy, catalytic selenite, and selenocystamine generated 8-hydroxydeoxyguanosine DNA adducts, induced apoptosis and were found to be cytotoxic in mouse keratinocytes. The noncatalytic selenomethionine was not cytotoxic, did not generate 8-hydroxydeoxyguanosine adducts and did not induce cellular apoptosis at any of the selenium concentrations studied. In keratinocytes, apoptosis may be initiated by superoxide (O2*-) and oxidative free radicals that are generated by selenite and selenocystamine, but not by selenomethionine.
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PMID:Selenium compounds have disparate abilities to impose oxidative stress and induce apoptosis. 989 Jun 39

The relationship among cancer growth, the glutathione redox cycle and the antioxidant system was studied in blood and in tumour cells. During cancer growth, the glutathione redox status (GSH/GSSG) decreases in blood of Ehrlich ascites tumour-bearing mice. This effect is mainly due to an increase in GSSG levels. Two reasons may explain the increase in blood GSSG: (a) the increase in peroxide production by the tumour that, in addition to changes affecting the glutathione-related and the antioxidant enzyme activities, can lead to GSH oxidation within the red blood cells; and (b) an increase of GSSG release from different tissues into the blood. GSH and peroxide levels are higher in the tumour cells when they proliferate actively, however GSSG levels remain constant during tumour growth in mice. These changes associate with low levels of lipid peroxidation in plasma, blood and the tumour cells. The GSH/GSSG ratio in blood also decreases in patients bearing breast or colon cancers and, as it occurs in tumour-bearing mice, this change associates with higher GSSG levels, especially in advanced stages of cancer progression. Our results indicate that determination of glutathione status and oxidative stress-related parameters in blood may help to orientate cancer therapy in humans.
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PMID:Changes in glutathione status and the antioxidant system in blood and in cancer cells associate with tumour growth in vivo. 989 33

The effect of dietary vitamin E on plasma, red blood cells (RBC), hepatic antioxidant status, and antioxidant enzyme activities was investigated. Three groups of six Sprague-Dawley rats were fed 0, 100, or 1,500 ppm vitamin E for eight weeks. Plasma alpha-tocopherol level was increased significantly by increasing dietary vitamin E (p < 0.05). Plasma lipid peroxidation (thiobarbituric acid-reactive substances) stimulation by 1 mM t-butyl hydroperoxide was correlated with dietary vitamin E level and was significantly greater in rats fed no vitamin E than in rats fed 100 or 1,500 ppm vitamin E (p < 0.05). RBC reduced glutathione (GSH) level was positively correlated with dietary vitamin E and was significantly greater in rats fed 1,500 ppm vitamin E than in rats fed 0 or 100 ppm vitamin E (p < 0.05). RBC oxidized glutathione was negatively correlated with dietary vitamin E. GSH redox status was expressed as the GSH-to-total GSH ratio; the ratio was also positively correlated with dietary vitamin E and was significantly greater in rats fed 1,500 ppm vitamin E than in rats fed no vitamin E (p < 0.05). For antioxidant enzymes, superoxide dismutase activity in hepatic cytosolic fraction was significantly greater in rats fed 1,500 ppm vitamin E than in rats fed 100 ppm vitamin E. Hepatic GSH reductase activity was significantly greater in rats fed 100 ppm vitamin E than in rats fed no vitamin E (p < 0.05). Dietary vitamin E had no effect on plasma vitamin C and protein thiol levels. In the systems studied, results indicated that dietary vitamin E selectively influences plasma vitamin E level, RBC GSH status, and hepatic cytosolic superoxide dismutase and GSH reductase activities.
Nutr Cancer 1998
PMID:Effect of dietary vitamin E on antioxidant status and antioxidant enzyme activities in Sprague-Dawley rats. 991 18

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3), the hormonal form of vitamin D, has anticancer activity in vivo and in vitro. Doxorubicin exerts its cytotoxic effect on tumor cells mainly by two mechanisms: (a) generation of reactive oxygen species (ROS); and (b) inhibition of topoisomerase II. We studied the combined cytotoxic action of 1,25(OH)2D3 and doxorubicin on MCF-7 breast cancer cells. Pretreatement with 1,25(OH)2D3 resulted in enhanced cytotoxicity of doxorubicin. The average enhancing effect after a 72-h pretreatment with 1,25(OH)2D3 (10 nM) followed by a 24-h treatment with 1 microg/ml doxorubicin was 74+/-9% (mean +/- SE). Under these experimental conditions, 1,25(OH)2D3 on its own did not affect cell number or viability. 1,25(OH)2D3 also enhanced the cytotoxic activity of another ROS generating quinone, menadione, but did not affect cytotoxicity induced by the topoisomerase inhibitor etoposide. The antioxidant N-acetylcysteine slightly reduced the cytotoxic activity of doxorubicin but had a marked protective effect against the combined action of 1,25(OH)2D3 and doxorubicin. These results indicate that ROS are involved in the interaction between 1,25(OH)2D3 and doxorubicin. 1,25(OH)2D3 also increased doxorubicin cytotoxicity in primary cultures of rat cardiomyocytes. Treatment of MCF-7 cells with 1,25(OH)2D3 alone markedly reduced the activity, protein, and mRNA levels of the cytoplasmic antioxidant enzyme Cu/Zn superoxide dismutase, which indicated that the hormone inhibits its biosynthesis. This reduction in the antioxidant capacity of the cells could account for the synergistic interaction between 1,25(OH)2D3 and doxorubicin and may also suggest increased efficacy of 1,25(OH)2D3 or its analogues in combination with other ROS-generating anticancer therapeutic modalities.
Cancer Res 1999 Feb 15
PMID:1,25-Dihydroxyvitamin D3 enhances the susceptibility of breast cancer cells to doxorubicin-induced oxidative damage. 1002 76

Although researchers in radiation and cancer biology have known about the existence of free radicals and their potential role in pathobiology for several decades, cardiac biologists only began to take notice of these noxious species in the 1970s. Exponential growth of free radical research occurred after the discovery of superoxide dismutase in 1969. This antioxidant enzyme is responsible for the dismutation of superoxide radical--a free radical chain initiator. A fine balance between free radicals and a variety of endogenous antioxidants is believed to exist. Any disturbance in this equilibrium in favour of free radicals causes an increase in oxidative stress and initiates subcellular changes leading to cardiomyopathy and heart failure. Our knowledge about the role of free radicals in the pathogenesis of cardiac dysfunction is fast approaching the point where newer therapies employing antioxidants are in sight.
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PMID:The role of oxidative stress in the genesis of heart disease. 1053 10

Flavonoids are reported to exhibit a wide variety of biological effects, including antioxidant and free radical-scavenging activities. Reactive oxygen species have been implicated in a range of human pathological diseases such as atherosclerosis and certain cancers. The aims of this present study were 1) to investigate the effect of the flavonoids myricetin, quercetin, and rutin on cell viability, endogenous antioxidant enzyme activities, and DNA integrity in Caco-2 and Hep G2 cells and 2) to determine whether these flavonoids could protect against H2O2-induced DNA damage. Both cell lines were supplemented with various concentrations (0-200 microM) of myricetin, quercetin, and rutin for 24 hours or H2O2 (50 microM) for 30 minutes, and cell viability was assessed. Over the concentration range tested, neither the flavonoids nor H2O2 significantly affected cell viability. The effect of the flavonoids on the activities of the antioxidant enzymes catalase (EC 1.11.1.6) and superoxide dismutase (EC 1.15.1.1) and on DNA integrity was assessed. The flavonoids did not significantly affect catalase or superoxide dismutase activity and did not induce DNA damage in either cell line. Exposure to 50 microM H2O2 for 30 minutes at 37 degrees C resulted in significant DNA damage, and preincubation with the flavonoids before H2O2 exposure significantly (p < 0.05) protected Caco-2 and Hep G2 cells against H2O2-induced DNA damage.
Nutr Cancer 1999
PMID:Protection by the flavonoids myricetin, quercetin, and rutin against hydrogen peroxide-induced DNA damage in Caco-2 and Hep G2 cells. 1057 83

We examined the effects of garlic oil (GO) and two of its organosulfur compounds, diallyl sulfide (DAS) and diallyl disulfide (DADS), on the drug-metabolizing and antioxidant systems in rats and sought to determine whether these effects are associated with dietary fat. Rats were fed a high-fat diet and received GO or DADS (200 mg/kg body wt) or DAS (100 mg/kg) orally three times a week for seven weeks. Control animals received corn oil alone. Another group of rats was fed a low-fat diet, with or without GO. GO and DADS significantly reduced the body weight gain of rats (p < 0.05). GO, however, dramatically increased the spleen weight and spleen weight-to-body weight ratio (p < 0.05). DAS increased glutathione S-transferase (GST) and 7-pentoxyresorufin O-dealkylase activities, whereas DADS increased only GST activity (p < 0.05). Immunoblot assay showed GO-, DAS-, and DADS-enhanced expression of the placental form of GST and cytochrome P-450 IIBI but suppressed cytochrome P-450 IIEI expression. Hepatic antioxidant enzyme activities were also modulated by these garlic components. GO and DADS inhibited glutathione peroxidase activity (p < 0.05), and DADS and DAS enhanced glutathione reductase activity (p < 0.05). Only GO enhanced the superoxide dismutase activity (p < 0.05). All these garlic components increased glutathione levels in red blood cells (p < 0.05) but did not influence hepatic glutathione levels. Although the amount of fat in the diet modulated drug-metabolizing and antioxidant functions, no interactions between GO and dietary fat were observed. These results indicate that GO and its allyl sulfide components, as well as dietary lipid, modulate drug-metabolizing and antioxidant enzyme activities. The action of GO appears to be independent of dietary lipid content.
Nutr Cancer 1999
PMID:Effects of garlic oil and its organosulfur compounds on the activities of hepatic drug-metabolizing and antioxidant enzymes in rats fed high- and low-fat diets. 1069 70

Although several immunohistochemical markers are available, differential diagnosis between mesothelioma and metastatic adenocarcinoma of the pleura is difficult. We have found that the immunoreactivity of manganese superoxide dismutase (MnSOD), an important antioxidant enzyme, is high in mesothelioma compared to healthy pleural mesothelium. The aim of the present study was to investigate whether MnSOD can be used in the differential diagnosis of malignant mesothelioma and metastatic adenocarcinoma of the pleura. MnSOD expression was assessed by using immunohistochemistry in biopsies of malignant mesothelioma (n = 35) and metastatic adenocarcinoma of the pleura (n = 21). MnSOD immunoreactivity was assessed semiquantitatively with and without microwave pretreatment. Fifteen of the 35 malignant mesotheliomas showed moderate or strong MnSOD expression without and 23 with microwave pretreatment, the corresponding figures for metastatic adenocarcinoma of the pleura being 1 and 2 out of 21 (P = 0.002 and P < 0.001, respectively by Fisher's exact test). Only mesothelioma biopsies showed strong MnSOD reactivity, and it was never negative in mesothelioma, whereas one-third of the adenocarcinomas showed no MnSOD reactivity. In conclusion, MnSOD immunoreactivity can, combined with other markers, aid the differential diagnosis between malignant mesothelioma and metastatic adenocarcinoma of the pleura.
Br J Cancer 2000 Mar
PMID:Manganese superoxide dismutase as a diagnostic marker for malignant pleural mesothelioma. 1073 84


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