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)

When the equilibrium between free-radical production and cellular antioxidant defences is disturbed in favour of more free radicals, it causes oxidative stress which can promote cellular injury. Oxidative stress has been suggested to play a role in the pathogenesis of diabetic cardiomyopathy. In streptozotocin-induced diabetes, there is a decrease in antioxidant enzyme activities and an increase in myocardial lipid peroxidation. Probucol, an antioxidant, was found to improve cardiac function which may have been due to an increase in myocardial antioxidant enzyme activities and a decrease in lipid peroxidation in the diabetic animals. Some of the beneficial effects of probucol may also be due to an improvement in plasma insulin levels and a decrease in the plasma glucose. The diabetic state is also associated with endothelial dysfunction, retinopathy, neuropathy and renopathy. Some of these secondary complications may also be mediated by oxidative stress. It is suggested that diabetic cardiomyopathy is associated with an antioxidant deficit and that antioxidant therapy may be useful in improving cardiac function in diabetes.
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PMID:Oxidative stress and functional deficit in diabetic cardiomyopathy. 1190 Mar 71

The importance of the antioxidant enzyme superoxide dismutase (CuZnSOD) in the metabolic switch from normotrophic to methylotrophic conditions was studied in the facultative methylotrophic yeast Candida boidinii. Copper adaptation was performed to qualify C. boidinii as a suitable cellular system to study the effect of induction of CuZnSOD, and other biochemical components along the copper detoxification system, on methanol adaptation. Copper adaptation results in the induction of CuZnSOD peroxidase activity as well as of glutathione. The effects at the metabolic level of exposure to both copper and methanol were also studied: the results suggest that the effect on antioxidant enzyme levels as a function of the change of trophic condition are predominant with respect to the effects of copper administration. Thus, the methanol-dependent induction of such enzymes is likely to provide a sufficient protection for the cells against toxic effects depending on copper administration. Administration of copper under methylotrophic conditions decreases the growth rate in spite of the high levels of antioxidant enzymes that are elicited by copper treatment. The adaptation to methanol metabolism was studied alsoafter methanol-independent induction of CuZnSOD, glutathione and catalase levels, obtained by exposure to high copper concentrations in glucose-containing medium. The metabolic changes induced by copper are persistent over several re-inoculations in normo-cupric glucose medium, thus allowing the study of the glucose-to-methanol switch on cells exhibiting high levels of antioxidant enzyme activities. Under such conditions the lag time observed during the transition from normotrophic to methylotrophic conditions is strongly reduced.
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PMID:Copper adaptation and methylotrophic metabolism in Candida boidinii. 1196 33

Patients with metabolic syndrome show augmented cardio-vascular risk, at least in part mediated through disequilibrium between mechanisms generating free radicals, and antioxidant defense. Carbohydrate and lipid disturbances in metabolic syndrome induce oxidative stress via several non fully understood mechanisms. Glucose overload in oral glucose tolerance test (OGTT) can also induce oxidative stress. The aim of our study was to evaluate changes in superoxide dismutase and glutathione peroxidase activity, as well as total antioxidant status in OGTT in patients with metabolic syndrome and in healthy subjects. OGTT was performed in 36 healthy volunteers and in patients with metabolic syndrome. Glucose, Insulin, and triglycerides were evaluated at 0th, 30th, 60th, 120th, and 180th min. Superoxide dismutase and glutathione peroxidase were measured at 0th, 60th, and 120th min. Total antioxidant status was measured at 0th, and 120th min. At 0th min total, HDL and LDL cholesterol were evaluated. A statistically significant decrease (p < 0.05) in superoxide dismutase activity at 120th as compared with 60th min were observed. Glutathione peroxidase activity decreased significantly (p < 0.05) even though at 60th as compared with 0th min and remained decreased at 120th min. Total antioxidant status was found to be increased (p < 0.05) at 120th as compared with 0th min. The observed dynamic in patients did not differed (p > 0.05) from control group. The study shows a decrease in antioxidant enzyme activity and a compensatory increase in total antioxidant status, indicating a surcharge of antioxidant homeostasis. In context of carbohydrate and lipid disturbances in metabolic syndrome, this is to suggest an existing of complementary pathogenic mechanisms, able to aggravate cardiovascular risk in these patients. Correction of metabolic disturbances may be an efficacious tool for influencing on prooxidant-antioxidant homeostasis too.
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PMID:[Antioxidant parameters in metabolic syndrome -- a dynamic evaluation during oral glucose tolerance test]. 1200 76

Nitric oxide (*NO) and its by-products modulate many physiological functions of skeletal muscle including blood flow, metabolism, glucose uptake, and contractile function. However, growing evidence suggests that an overproduction of nitric oxide contributes to muscle wasting in a number of pathologies including chronic heart failure, sepsis, COPD, muscular dystrophy, and extreme disuse. Limited data point to the potential of inhibition various enzymes by reactive nitrogen species (RNS), including (.)NO and its downstream products such as peroxynitrite, primarily in purified systems. We hypothesized that exposure of skeletal muscle to RNS donors would reduce or downregulate activities of the crucial antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX). Diaphragm muscle fiber bundles were extracted from 4-month-old Fischer-344 rats and, in a series of experiments, exposed to either (a) 0 (control), 1, or 5 mM diethylamine NONOate (DEANO: *NO donor); (b) 0, 100, 500 microM, or 1 mM sodium nitroprusside (SNP: *NO donor); (c) 0 or 2 mM S-nitroso-acetylpenicillamine (SNAP: *NO donor); or (d) 0 or 500 microM SIN-1 (peroxynitrite donor) for 60 min. DEANO resulted in a 50% reduction in CAT, GPX, and a dose-dependent inhibition of Cu, Zn-SOD. SNP resulted in significantly lower activities for total SOD, Mn-SOD isoform, Cu, Zn-SOD isoform, CAT, and GPX in a dose-dependent fashion. Two millimolar SNAP and 500 microM SIN-1 also resulted in a large and significant inhibition of total SOD and CAT. These data indicate that reactive nitrogen species impair antioxidant enzyme function in an RNS donor-specific and dose-dependent manner and are consistent with the hypothesis that excess RNS production contributes to skeletal muscle oxidative stress and muscle dysfunction.
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PMID:Specificity of antioxidant enzyme inhibition in skeletal muscle to reactive nitrogen species donors. 1207 89

Glucocorticoids (GCs), the adrenal steroids secreted during stress, compromise the ability of hippocampal neurons to survive various necrotic insults. We have previously observed that GCs enhance the hippocampal neurotoxicity of reactive oxygen species and, as a potential contributor to this, decrease the activity of the antioxidant enzyme, glutathione peroxidase (GSPx). In this report, we have studied the possible mechanisms underlying this GC effect upon GSPx in primary hippocampal cultures and have observed several results. (i) Corticosterone (the GC of rats) decreased glutathione levels; this was predominately a result of a decrease in levels of reduced glutathione (GSH), the form of glutathione which facilitates GSPx activity. (ii) Corticosterone also decreased levels of NADPH; this may help explain the effect on GSH as NADPH is required for regeneration of GSH from oxidized glutathione. (iii) However, the corticosterone effect on total glutathione levels could not just be caused by the NADPH effect, as there were also reduced levels of oxidized glutathione. (iv) Corticosterone caused a small but significant decrease in GSPx activity over a range of glucose concentrations; this occurred under circumstances of an excess of glutathione as a substrate, suggesting a direct effect of corticosterone on GSPx activity. (v) This corticosterone effect was likely to have functional implications, in that enhancement of GSPx activity (to the same magnitude as activity was inhibited by corticosterone) by GSPx overexpression protected against an excitotoxin. Thus, GCs have various effects, both energetic and non-energetic in nature, upon steps in GSPx biochemistry that, collectively, may impair hippocampal antioxidant capacity.
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PMID:Disruptive effects of glucocorticoids on glutathione peroxidase biochemistry in hippocampal cultures. 1209 72

Humics and pesticides are present in aquatic environment and the toxicological consequences of their chemical interaction is well studied. However, data concerning the mechanism of the biochemical action of humic-pesticide combinations are scarce, especially in vertebrates. Thus we have chosen to study the in vivo effects of the plant polyphenolic tannic acid and the pyrethroid insecticide deltamethrin [Decis] alone or in combination on hepatic xenobiotic-metabolizing enzyme activities and the associated redox-parameters in carp, as the complex assessment of these systems are regarded to serve as a relevant biomarker of environmental pollution. Stress effects and tissue damage were followed by determination of the plasma glucose level, the activities of plasma transaminases, and by electron microscopy. Tannic acid alone exerted weak prooxidant effect due to its marked antioxidant enzyme inhibitory activity. Deltamethrin, applied in a very low dose, induced oxyradical production in fish via activation of cytochrome P450 isozymes. This effect was promoted by the antioxidant enzyme inhibitory action of tannic acid, when the two chemicals were combined; however, the ultrastructural damage of the hepatocytes was reduced by the common cytoprotective capacity of the phenolic. Numerous humics are known to alter the toxicity of pesticides and their influence depends on their type and concentration. Therefore, our work taken together with other comparative studies may contribute to the assessment of the impact of humics in nature, especially in case of environmental pollution.
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PMID:Influence of the polyphenolic tannic acid on the toxicity of the insecticide deltametihrin to fish. A comparative study examining both biochemical and cytopathological parameters. 1237 15

The possible repercussions of osmoregulatory processes on some indicators of classical and oxidative stress were examined during gradual acclimation of sturgeons (Acipenser naccarii) to full seawater (35% salinity) and after a period of 20 approximately days at this salinity. Erythrocyte constants and levels of cortisol, protein and glucose in the plasma were determined. In addition, plasma osmolality and muscle-hydration values, as well as liver and heart protein, were determined. Catalase, glutathione peroxidase and superoxide dismutase activities and lipidperoxidation levels were measured in blood (plasma and red blood cells) and tissue (liver and heart). A number of physiological responses, such as disturbance in body fluid, activation of osmoregulatory mechanisms, augmented antioxidant defences in blood and alteration of energy metabolites, were detected with increasing environmental salinity. After 20 days at 35% salinity, plasma osmolality, erythrocyte constants and muscle water content all returned to values usual for low environmental salinity, indicating that osmoregulatory processes have achieved their objective. However, cortisol values, antioxidant enzyme activities in the blood (plasma and red blood cells), lipid peroxidation in plasma, and hepatic proteins did not return to initial values, showing that osmoregulatory processes cause major physiological changes in the fish.
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PMID:Physiological changes of sturgeon Acipenser naccarii caused by increasing environmental salinity. 1240 96

Lipid disorders and increased oxidative stress may exacerbate some complications of diabetes mellitus. Previous studies have implicated the beneficial effects of some antioxidants, omega-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the protection of cells from the destructive effect of increased lipids and lipid peroxidation products. This study, therefore, was designed to investigate the effects of cod liver oil (CLO, Lysi Ltd. Island), which comprises mainly vitamin A, PUFAs, EPA and DHA. Effects were monitored on plasma lipids, lipid peroxidation products (MDA) and the activities of antioxidant enzymes, glutathione peroxidase (GSHPx) and catalase in heart, liver, kidney and lung of non-diabetic control and streptozotocin (STZ)-induced-diabetic rats. Two days after STZ-injection (55 mg kg(-1) i.p.), non-diabetic control and diabetic rats were divided randomly into two groups as untreated or treated with CLO (0.5 ml kg(-1) rat per day) for 12 weeks. Plasma glucose, triacylglycerol and cholesterol concentrations were significantly elevated in 12-week untreated-diabetic animals; CLO treatment almost completely prevented these abnormalities in triacylglycerol and cholesterol, but hyperglycaemia was partially controlled. CLO also provided better weight gain in diabetic animals. In untreated diabetic rats, MDA markedly increased in aorta, heart and liver but was not significantly changed in kidney and lung. This was accompanied by a significant increase in both GSHPx and catalase enzyme activities in aorta, heart, and liver of diabetic rats. In kidney and lung, diabetes resulted in reduced catalase while GSHPx was significantly activated. In aorta, heart, and liver, diabetes-induced changes in MDA were entirely prevented by CLO treatment. In the tissues of CLO-treated diabetic animals, GSHPx activity paralleled those of control animals. CLO treatment also caused significant improvements in catalase activities in every tissue of diabetic rats, but failed to affect MDA and antioxidant activity in control animals. The current study suggests that the treatment of diabetic rats with CLO provides better control of glucose and lipid metabolism, allows recovery of normal growth rate, prevents oxidative/peroxidative stress and ameliorates endogenous antioxidant enzyme activities in various tissues. Because CLO contains a plethora of beneficial compounds together, its use for the management of diabetes-induced complications may provide important advantages.
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PMID:Effects of cod liver oil on tissue antioxidant pathways in normal and streptozotocin-diabetic rats. 1241 63

Determination of reliable bioindicators of diabetes-induced oxidative stress and the role of dietary vitamin E supplementation were investigated. Blood (plasma) chemistries, lipid peroxidation (LPO), and antioxidant enzyme activities were measured over 12 weeks in New Zealand White rabbits (control, diabetic, and diabetic + vitamin E). Cholesterol and triglyceride levels did not correlate with diabetic state. Plasma LPO was influenced by diabetes and positively correlated with glucose concentration only, not cholesterol or triglycerides. Liver glutathione peroxidase (GPX) activity negatively correlated with glucose and triglyceride levels. Plasma and erythrocyte GPX activities positively correlated with glucose, cholesterol, and triglyceride concentrations. Liver superoxide dismutase activity positively correlated with glucose and cholesterol concentration. Vitamin E reduced plasma LPO, but did not affect the diabetic state. Thus, plasma LPO was the most reliable indicator of diabetes-induced oxidative stress. Antioxidant enzyme activities and types of reactive oxygen species generated were tissue dependent. Diabetes-induced oxidative stress is diminished by vitamin E supplementation.
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PMID:Differential indicators of diabetes-induced oxidative stress in New Zealand White rabbits: role of dietary vitamin E supplementation. 1245 60

The neuropathology of Parkinson's disease (PD) involves a reduction of endogenous antioxidant enzyme systems, heightened oxidative stress and mitochondrial aberrations in the region of the substantia nigra. Similarly, neurotoxins commonly used to investigate PD pathology include 6-hydroxydopamine (6-OHDA), a powerful hydrogen peroxide (H(2)0(2)) pro-oxidant and 1-methyl-4-phenylpyridinium ion (MPP+), a mitochondrial complex I inhibitor that exerts detrimental effects on cellular energy production. Pyruvic acid is a neuronal metabolic energy fuel that can also rapidly undergo decarboxylation to diffuse H(2)0(2) into H(2)0. In this study, we investigated the effect of pyruvic acid against 6-OHDA, MPP+ and H(2)0(2) toxicity in murine brain neuroblastoma cells. The results obtained indicated that the toxicity of 6-OHDA was inversely related to the autoxidative formation of H(2)0(2). Pyruvic acid exhibited powerful non-enzymatic stoichiometric H(2)0(2) trapping properties, and protected against both 6-OHDA and H(2)0(2) toxicity. While both sodium pyruvate and pyruvate were highly protective against oxidative stress, pyruvate in its free acid form only was protective against MPP+, indicating a requirement for effective transport in order to fuel glycolysis. The protective properties of glucose were compared to pyruvic acid, and the data indicated that glucose did not exhibit antioxidant properties and was effective in blocking MPP+, but not 6-OHDA or H(2)0(2) toxicity. On the other hand, pyruvic acid was protective against all three toxins, and unlike glucose, completely blocked MPP+ toxicity in a combination insult model with up to 500 microM of H(2)0(2). Moreover, the data obtained indicate that pyruvic acid exerts powerful neuroprotective properties by providing simultaneous resistance to oxidative stress and mitochondrial insult. These protective effects are the result of a unique dual property of pyruvic acid with concurrent ability to serve as an effective neuronal energy substrate for glycolysis and to act as an exceptionally powerful antioxidant.
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PMID:Pyruvic acid cytoprotection against 1-methyl-4-phenylpyridinium, 6-hydroxydopamine and hydrogen peroxide toxicities in vitro. 1252 92


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