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 an essential trace element that up-regulates a major component of the antioxidant defense mechanism by controlling the body's glutathione (GSH) pool and its major Se-containing antioxidant enzyme, glutathione peroxidase (GPX). Evidence has emerged suggesting that organic selenium, natural seleno-amino acids found in plants, grains and selenized yeast, maintains the antioxidant defense system more efficiently than inorganic selenium. Inorganic selenium is a pro-oxidant, whereas organic selenium possesses antioxidant properties itself. As a pro-oxidant, inorganic selenium is not suitable for animals or humans. Therefore, we examined the GSH-GPX system in broiler chickens and determined that organic selenium was indeed more beneficial than inorganic selenium. Chickens fed the organic selenium as Sel-Plex, a selenized yeast, had elevated GPX activity in both blood and liver in a thermoneutral environment and after heat distress. More importantly, the ability to reduce the oxidized glutathione (GSSG to 2 GSH) was enhanced and facilitated by maintenance of glutathione reductase activity. Organic selenium-fed chickens were less affected by mild heat distress than inorganic selenium-fed chickens, and this assessment was based upon less induction of heat shock protein 70 (hsp70) in organic selenium-fed chickens. Our results clearly show that heat distress, a potent inducer of oxidative stress and hsp70, can be partially ameliorated by feeding organic selenium. We attribute this observation to an enhanced GSH-GPX antioxidant system in organic selenium-fed chickens.
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PMID:Influence of selenium sources on age-related and mild heat stress-related changes of blood and liver glutathione redox cycle in broiler chickens (Gallus domesticus). 1466 14

The first-trimester human placenta has limited antioxidant enzyme capacity. We investigated the distribution and transfer pathways of antioxidant molecules inside the first trimester gestational sac. The coelomic fluid of the exocoelomic cavity, which borders the inside of the first-trimester placenta, contained a very low level of reduced glutathione. Glutathione disulfide was undetectable in most coelomic samples, suggesting that the role of glutathione-related detoxification system is limited in fetal fluid compartments. The coelomic fluid contained similar concentrations of ascorbic and uric acid to maternal plasma. The levels of alpha- and gamma-tocopherol were lower in coelomic fluid, compared with maternal plasma. The presence of these molecules inside the early gestational sac suggests that they may play an essential role in the fetal tissues' antioxidant capacity at a time when the fetus is most vulnerable to oxidative stress. We also demonstrated by immunostaining the presence of alpha-tocopherol transfer protein in the cytoplasm of trophoblastic cells, glandular epithelium of the decidua, and mesothelial layer of the secondary yolk sac. This finding indicates that the uterine glands and the secondary yolk sac play key roles in supplying this essential vitamin to the developing fetus before the placental circulations are established.
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PMID:Distribution and transfer pathways of antioxidant molecules inside the first trimester human gestational sac. 1500 47

We have studied the activities of enzymes (glucose-6-phosphate dehydrogenase (G-6-PD), copper, zinc-superoxide dismutase (Cu,Zn-SOD), catalase (CAT), selenium-dependent glutathione peroxidase (Se-GSH-Px) and glutathione-S-transferase (GST)), and the levels of reduced glutathione (GSH), oxidized glutathione (GSSG) and thiobarbituric acid-reactive substances (TBARS) in rat erythrocytes and estimated the ratio of GSH/GSSG and the redox index. Male Wistar rats at ages of 1, 6 and 12 months were used. The activities of G-6-PD and Cu,Zn-SOD, the levels of GSSG and TBARS were increased, while the activity of Se-GSH-Px and the level of GSH were decreased with age. GSH/GSSG ratio was significantly decreased with age. We found a positive correlation between age and G-6-PD (r=0.476, p<0.01), Cu,Zn-SOD (r=0.291, p<0.01), CAT (r=0.254, p<0.01) and GST activities (r=0.250, p<0.05), and GSSG (r=0.708, p<0.05) and TBARS levels (r=0.802, p<0.01), whereas the correlation between age and Se-GSH-Px activity (r=-0.376, p<0.05), GSH level (r=-0.603, p<0.01) and GSH/GSSG ratio (r=-0.685, p<0.05) were negative. We found age-related differences in erythrocyte antioxidant enzyme activities, GSH, GSSG, total GSH and TBARS levels, GSH/GSSG ratio and the redox index.
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PMID:Changes in glucose-6-phosphate dehydrogenase, copper, zinc-superoxide dismutase and catalase activities, glutathione and its metabolizing enzymes, and lipid peroxidation in rat erythrocytes with age. 1503 14

Resting and exercised (both acute and chronic) hindlimb skeletal muscle from long-lived Ames dwarf and wild type mice at 3, 12, 18, and 24 months of age was tested for antioxidant enzyme activity and protein, non-enzymatic antioxidant ratios, mitochondrial hydrogen peroxide concentration, and plasma lactate levels. Differences were observed in GPX enzyme activity between mouse genotypes at all physical activity levels, with dwarf mice exhibiting depressed levels at younger ages (3 months: P = 0.09 [non-swim], P = 0.03 [acute swim], P = 0.04 [chronic swim]) and comparatively higher levels than wild type mice at older ages (18-24 months: P = 0.05 [acute swim], P = 0.07 [chronic swim]). Catalase enzyme activity and the GSH system rarely demonstrated significant differences between genotypes, regardless of age or activity. However, the chronic exercise group displayed a difference in GSH:GSSG ratios between mouse genotypes (P = 0.005). Plasma lactate concentrations were elevated in the wild type mice compared to the dwarf mice at all ages in all activity groups. These results suggest there are biological differences with regard to antioxidant defense that favor the Ames dwarf mouse in active and resting skeletal muscle when compared to wild type mice.
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PMID:Long-lived Ames dwarf mouse exhibits increased antioxidant defense in skeletal muscle. 1506 2

Biological aging is associated with increased cellular levels of reactive oxygen species (ROS) as well as the formation and accumulation of oxidized biomolecules. During evolution, organisms developed a highly-efficient and adaptive antioxidant defense system. Antioxidants can generally be divided into two categories: enzymatic and non-enzymatic. During the aging process the activity of antioxidant enzymes, e.g. SOD, CAT, GSH-Px, and GSSG-R, depends on factors such as race, gender, tissue and subcellular localization of enzymes. The age-dependent decrease in antioxidant enzyme activity may be attributed to oxidative modifications of enzymes. During the aging process, ROS may also lead to the induction of some enzyme activity which is explained as an adaptive phenomenon. The decrease in GSH concentration with age can be explained by decreased GSH synthesis and/or increased GSH consumption in the removal of peroxides and xenobiotics. In plasma albumin, ferritin, transferrin, and caeruloplasmin exert protective action. Plasma proteins can inhibit ROS generation and lipid peroxidation by chelating free transition metals. Plasma protein concentrations changes with age. The major exogenous antioxidants, mostly derived from the diet, are vitamin E, C, A, and beta-carotene. During the aging process the level of vitamins may decrease or increase, depending on such factors as diet, and diseases.
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PMID:[Antioxidative abilities during aging]. 1507 54

Carboplatin is currently being used as an anticancer drug against human cancers. However, high dose of carboplatin chemotherapy resulted in hearing loss in cancer patients. We have shown that carboplatin-induced hearing loss was related to dose-dependent oxidative injury to the cochlea in rat model. However, the time response of ototoxic dose of carboplatin on hearing loss and oxidative injury to cochlea has not been explored. The aim of the study was to evaluate the time response of carboplatin-induced hearing loss and oxidative injury to the cochlea of the rat. Male Wistar rats were divided into two groups of 30 animals each and treated as follows: (1) control (normal saline, i.p.) and (2) carboplatin (256 mg/kg, a single i.p. bolus injection). Auditory brain-evoked responses (ABRs) were recorded before and 1-5 days after treatments. The animals (n = 6) from each group were sacrificed on day 1, 2, 3, 4, and 5 and cochleae were isolated and analyzed. Carboplatin significantly elevated the hearing thresholds to clicks and to 2, 4, 8, 16, and 32 kHz tone burst stimuli only 3-5 days post-treatment. Carboplatin significantly increased nitric oxide (NO), malondialdehyde (MDA) levels and manganese superoxide dismutase (Mn-SOD) activity in the cochlea 4-5 and 3-5 days post-treatment, respectively, indicating enhanced influx of free radicals and oxidative injury to the cochlea. Carboplatin significantly depressed the reduced to oxidized glutathione (GSH/GSSG) ratio, antioxidant enzyme activities such as copper/zinc-superoxide dismutase (CuZn-SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) as well as enzyme protein expressions in the cochlea 3-5 days after treatment. The data suggest that carboplatin-induced hearing loss involves oxidative injury to the cochlea of the rat in a time-dependent manner.
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PMID:Time response of carboplatin-induced hearing loss in rat. 1510 10

Cardiovascular complications associated with 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) abuse have increasingly been reported. The indirect effect of MDMA mediated by a sustained high level of circulating biogenic amines may contribute to the cardiotoxic effects, but other factors, like the direct toxic effects of MDMA and its metabolites in cardiac cells, remain to be investigated. Thus, the objective of the present in vitro study was to evaluate the potential cardiotoxic effects of MDMA and its major metabolites 3,4-methylenedioxyamphetamine (MDA), N-methyl-alpha-methyldopamine (N-Me-alpha-MeDA), and alpha-methyldopamine (alpha-MeDA) using freshly isolated adult rat cardiomyocytes. The cell suspensions were incubated with these compounds in the final concentrations of 0.1, 0.2, 0.4, 0.8, and 1.6 mM for 4 h. alpha-MeDA, N-Me-alpha-MeDA, and their respective aminochromes (oxidation products) were quantified in cell suspensions by HPLC-DAD. The toxic effects were evaluated at hourly intervals for 4 h by measuring the percentage of cells with normal morphology, glutathione (GSH), and glutathione disulfide (GSSG); intracellular Ca(2+), ATP, and ADP; and the cellular activities of glutathione peroxidase, glutathione reductase, and glutathione-S-transferase. No toxic effects were found after exposure of rat cardiomyocytes to MDMA or MDA at any of the tested concentrations for 4 h. In contrast, their catechol metabolites N-Me-alpha-MeDA and alpha-MeDA induced significant toxicity in rat cardiomyocytes. The toxic effects were characterized by a loss of normal cell morphology, which was preceded by a loss of GSH homeostasis due to conjugation of GSH with N-Me-alpha-MeDA and alpha-MeDA, sustained increase of intracellular Ca(2+) levels, ATP depletion, and decreases in the antioxidant enzyme activities. The oxidation of N-Me-alpha-MeDA and alpha-MeDA into the toxic compounds N-methyl-alpha-methyldopaminochrome and alpha-methyldopaminochrome, respectively, was also verified in cell suspensions incubated with these MDMA metabolites. The results obtained in this study provide evidence that the metabolism of MDMA into N-Me-alpha-MeDA and alpha-MeDA is required for the expression of MDMA-induced cardiotoxicity in vitro, being N-Me-alpha-MeDA the most toxic of the studied metabolites.
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PMID:Metabolism is required for the expression of ecstasy-induced cardiotoxicity in vitro. 1514 19

Reactive oxygen species (ROS) play a role in male infertility, where excessive amounts impair spermatozoal motility. Epididymal antioxidant enzymes protect spermatozoa from oxidative damage in the epididymal lumen. Antioxidant secretions from the seminal vesicle protect spermatozoa after ejaculation. As it is known that with age there is increased generation of ROS, the goals of this study were to determine how aging affects the response of antioxidant enzymes in the epididymis, seminal vesicles, and liver to l-buthionine-S,R-sulfoximine (BSO) mediated glutathione (GSH) depletion, and to examine the impact of GSH depletion on motility parameters of spermatozoa from the cauda epididymidis in young (4-mo-old) and old (21-mo-old) rats. Levels of GSH and glutathione disulfide (GSSG), as well as activities of glutathione peroxidase, glutathione reductase, catalase, and superoxide dismutase, were measured in the caput, corpus and cauda epididymidis, seminal vesicles, and liver. Spermatozoal motility was assessed by computer-assisted sperm analysis. Significant age-related changes in antioxidant enzyme activities were found in the liver and cauda epididymidis. Glutathione depletion clearly affected tissues in both young and old. The compounding effect of age was most evident in the cauda epididymidis, seminal vesicles, and liver, where antioxidant enzyme activities changed significantly. Additionally, spermatozoa motility was adversely affected after BSO treatment in both age groups, but significantly more so in older animals. In summary, the male reproductive tissues and liver undergo age-related changes in antioxidant enzyme activities and in their response to GSH depletion.
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PMID:Effect of glutathione depletion on antioxidant enzymes in the epididymis, seminal vesicles, and liver and on spermatozoa motility in the aging brown Norway rat. 1515 30

In the past decade, clinical evidence has increasingly shown that the liver is a target organ for 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") toxicity. The aims of the present in vitro study were: (1) to evaluate and compare the hepatotoxic effects of MDMA and one of its main metabolites, N-methyl-alpha-methyldopamine (N-Me-alpha-MeDA) and (2) to investigate the ability of antioxidants, namely ascorbic acid and N-acetyl-L-cysteine (NAC), to prevent N-Me-alpha-MeDA-induced toxic injury, using freshly isolated rat hepatocytes. Cell suspensions were incubated with MDMA or N-Me-alpha-MeDA in the final concentrations of 0.1, 0.2, 0.4, 0.8, and 1.6 mM for 3 h. To evaluate the potential protective effects of antioxidants, cells were preincubated with ascorbic acid in the final concentrations of 0.1 and 0.5 mM, or NAC in the final concentrations of 0.1 and 1 mM for 15 min before treatment with 1.6 mM N-Me-alpha-MeDA for 3 h (throughout this incubation period the cells were exposed to both compounds). The toxic effects were evaluated by measuring the cell viability, glutathione (GSH) and glutathione disulfide (GSSG), ATP, and the cellular activities of GSH peroxidase (GPX), GSSG reductase (GR), and GSH S-transferase (GST). MDMA induced a concentration- and time-dependent GSH depletion, but had a negligible effect on cell viability, ATP levels, or on the activities of GR, GPX, and GST. In contrast, N-Me-alpha-MeDA was shown to induce not only a concentration- and time-dependent depletion of GSH, but also a depletion of ATP levels accompanied by a loss in cell viability, and decreases in the antioxidant enzyme activities. For both compounds, GSH depletion was not accompanied by increases in GSSG levels, which seems to indicate GSH depletion by adduct formation. Importantly, the presence of ascorbic acid (0.5 mM) or NAC (1 mM) prevented cell death and GSH depletion induced by N-Me-alpha-MeDA. The results provide evidence that MDMA and its metabolite N-Me-alpha-MeDA induce toxicity to freshly isolated rat hepatocytes. Oxidative stress may play a major role in N-Me-alpha-MeDA-induced hepatic toxicity since antioxidant defense systems are impaired and administration of antioxidants prevented N-Me-alpha-MeDA toxicity.
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PMID:The toxicity of N-methyl-alpha-methyldopamine to freshly isolated rat hepatocytes is prevented by ascorbic acid and N-acetylcysteine. 1521 15

Reduced and oxidized glutathione (GSH and GSSG), protein-bound glutathione, lipid peroxidation and antioxidant enzyme activities were determined in the erythrocyte lysates and membranes of type I and II alcoholics in order to clarify the effect of age-of-onset and the duration of the alcohol consumption on erythrocyte oxidant and antioxidant status. The osmotic fragility and susceptibility of the erythrocytes to haemolysis were also determined. Erythrocyte lipid peroxidation was significantly increased but, GSH and protein-bound GSH, GSH/GSSG ratio and antioxidant enzyme activities were markedly decreased in the erythrocytes of the alcoholic subgroups. Erythrocyte count and haemoglobin content in the blood of alcoholics were found to be decreased in accordance with the finding that erythrocytes were more fragile and less resistant to haemolysis particularly in type II alcoholics. The present study showed that ethanol-induced oxidative stress in erythrocytes can lead to haemolysis and membrane-specific injuries in erythrocytes of the alcoholic subtypes.
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PMID:Lipid peroxidation and antioxidant enzyme activities in erythrocytes of type I and II alcoholics. 1538 40


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