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)

Antioxidant enzymes have shown promise as a therapy for pathological conditions involving increased production of reactive oxygen species (ROS). However the efficiency of their use for combating oxidative stress is dependent on the ability to achieve therapeutically adequate levels of active enzymes at the site of ROS-mediated injury. Thus, the implementation of antioxidant enzyme therapy requires a strategy enabling both guided delivery to the target site and effective protection of the protein in its active form. To address these requirements we developed magnetically responsive nanoparticles (MNP) formed by precipitation of calcium oleate in the presence of magnetite-based ferrofluid (controlled aggregation/precipitation) as a carrier for magnetically guided delivery of therapeutic proteins. We hypothesized that antioxidant enzymes, catalase and superoxide dismutase (SOD), can be protected from proteolytic inactivation by encapsulation in MNP. We also hypothesized that catalase-loaded MNP applied with a high-gradient magnetic field can rescue endothelial cells from hydrogen peroxide toxicity in culture. To test these hypotheses, a family of enzyme-loaded MNP formulations were prepared and characterized with respect to their magnetic properties, enzyme entrapment yields and protection capacity. SOD- and catalase-loaded MNP were formed with average sizes ranging from 300 to 400 nm, and a protein loading efficiency of 20-33%. MNP were strongly magnetically responsive (magnetic moment at saturation of 14.3 emu/g) in the absence of magnetic remanence, and exhibited a protracted release of their cargo protein in plasma. Catalase stably associated with MNP was protected from proteolysis and retained 20% of its initial enzymatic activity after 24h of exposure to pronase. Under magnetic guidance catalase-loaded MNP were rapidly taken up by cultured endothelial cells providing increased resistance to oxidative stress (62+/-12% cells rescued from hydrogen peroxide induced cell death vs. 10+/-4% under non-magnetic conditions). We conclude that non-polymeric MNP formed using the controlled aggregation/precipitation strategy are a promising carrier for targeted antioxidant enzyme therapy, and in combination with magnetic guidance can be applied to protect endothelial cells from oxidative stress mediated damage. This protective effect of magnetically targeted MNP impregnated with antioxidant enzymes can be highly relevant for the treatment of cardiovascular disease and should be further investigated in animal models.
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PMID:Endothelial delivery of antioxidant enzymes loaded into non-polymeric magnetic nanoparticles. 2048 66

Clinical use of doxorubicin continues to be challenged by its undesirable systematic toxicity, caused mainly by oxidative stress. The aim of this study was to investigate the effectiveness of fullerenol C(60)(OH)(24) polyanion nanoparticles, an antioxidant agent, against doxorubicin-induced nephro-, testicular, and pulmonary toxicity. Results obtained in vitro suggest that fullerenol's anti-proliferative property and protective effect against doxorubicin cytotoxicity are mediated by the antioxidative and radical scavenging activity. Male Wistar rats were divided into five treatment groups: the control group (I) received 0.9% NaCl (1 mL/kg, i.p.). Groups II, III, IV, and V received a single dose of doxorubicin (10 mg/kg i.p.), doxorubicin/fullerenol (100 and 50 mg/kg i.p. of fullerenol 30 min prior to 10 mg/kg i.p. of doxorubicin), and fullerenol (100 mg/kg i.p.), respectively. On the 2(nd) and 14(th) days, organ samples were taken for the measurement of lipid peroxidation and activities of superoxide dismutase, catalase, glutathione-peroxidase, -reductase, and -transferase. Doxorubicin induced a significant increase of lipid peroxidation and alterations of antioxidant enzyme activities, while the fullerenol pre-treatment prevented the effects of doxorubicin on investigated parameters. Fullerenol, applied alone, did not alter basal values of the investigated animals. Considering the mechanisms of doxorubicin toxicity, it can be concluded that fullerenol exerts its protective role by acting as a free radical sponge and/or by removing free iron through formation of fullerenol-iron complex. Results of this study support the hypothesis of testicular, pulmo-, and nephroprotective efficacy of fullerenol in preventing oxidative stress induced by doxorubicin.
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PMID:Antioxidant properties of fullerenol C60(OH)24 in rat kidneys, testes, and lungs treated with doxorubicin. 2049 20

The aim of the present study is to evaluate the status of plasma essential trace elements magnesium (Mg), copper (Cu), zinc (Zn), iron (Fe) and selenium (Se) concentrations and their some related antioxidant enzyme activities, erythrocyte glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) activities in patients with Alzheimer's disease (AD). Fifty patients with AD and fifty healthy control subjects were included in this study. Plasma Cu and Zn concentrations by atomic absorption spectrometry (AAS), plasma Mg and Fe concentrations by spectrophotometric methods and plasma Se concentrations by graphite furnace AAS were determined. Erythrocyte GPx, SOD and CAT activities were measured by spectrophotometric methods. Plasma Mg, Cu, Zn, Fe and Se levels and erythrocyte GPx, SOD and CAT activities were found to be significantly lower in patients with AD compared with controls. These results suggest that alterations in essential trace elements and their related enzymes may play a role in the etiopathogenesis of AD. Also, there is a defect in the antioxidant defense system, which may lead to oxidative damage in patients with AD. The changes in antioxidant enzyme activities may be secondary to the alterations in their cofactor concentrations.
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PMID:Alterations of plasma magnesium, copper, zinc, iron and selenium concentrations and some related erythrocyte antioxidant enzyme activities in patients with Alzheimer's disease. 2056 29

In the central nervous system (CNS), iron is enriched in oligodendrocytes, the myelin forming cells. The importance of iron in CNS myelination has been demonstrated by studies using rodent models, in which iron deficiency is associated with hypomyelination. Besides iron deficiency, an abnormal iron accumulation is thought to be involved in the pathogenesis of demyelination in multiple sclerosis, an autoimmune demyelinating disease in humans. To determine the importance of iron metabolism in myelin diseases, we investigated iron metabolism using two different myelin mutant dmy (demyelination model) and mv (hypomyelination model) rats. Our results demonstrated an abnormal iron deposition, and significant upregulation of antioxidant enzyme heme oxygenase-1 (HO-1) and iron storage protein ferritin in the dmy rat, but not in the mv rat. The expression of iron transporter transferrin mRNA was significantly decreased in the mv but not dmy rat, which may reflect a part of functional abnormalities of oligodendrocytes in the mv rat. Iron accumulation and increased expression of ferritin in the dmy rat were mainly found in astrocytes, suggesting a protective role of astrocytes in iron-mediated cytotoxicity. HO-1 was predominantly induced in oligodendrocytes during the early stage of demyelination in the dmy rat, suggesting that iron-mediated oxidative stress is most likely involved in the pathogenesis of demyelination in the dmy rat.
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PMID:Abnormal iron accumulation is involved in the pathogenesis of the demyelinating dmy rat but not in the hypomyelinating mv rat. 2059 39

The antioxidant enzyme manganese superoxide dismutase (SOD2) serves as the primary defense against mitochondrial superoxide. Impaired SOD2 activity in murine hematopoietic cells affects erythroid development, resulting in anemia characterized by intra-mitochondrial iron deposition, reticulocytosis and shortened red cell life span. Gene expression profiling of normal and SOD2 deficient erythroblasts identified the Parkinson's disease locus DJ-1 (Park7) as a differentially expressed transcript. To investigate the role of DJ-1 in hematopoietic cell development and protection against oxidative stress caused by Sod2 loss, we evaluated red cell parameters, reticulocyte count, red cell turnover and reactive oxygen species production in DJ-1 knockout animals and chimeric animals lacking both SOD2 and DJ-1 in hematopoietic cells generated by fetal liver transplantation. We also investigated DJ-1 protein expression in primary murine erythroid and erythroleukemia cells (MEL). Loss of DJ-1 exacerbates the phenotype of SOD2 deficiency, increasing reticulocyte count and decreasing red cell survival. Using MEL cells, we show that DJ-1 is up-regulated at the protein level during erythroid differentiation. These results indicate that DJ-1 plays a physiologic role in protection of erythroid cells from oxidant damage, a function unmasked in the context of oxidative stress.
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PMID:The familial Parkinson's disease gene DJ-1 (PARK7) is expressed in red cells and plays a role in protection against oxidative damage. 2080 May 16

We compared the bioaccumulation of lead (Pb), cadmium (Cd), zinc (Zn), copper (Cu), nickel (Ni) and iron (Fe) with antioxidant enzyme activity in tissues of the snails, Lymnaea natalensis, exposed to elements of two differently polluted dams. 45 snails were exposed to sediment and water collected from Wight Dam (reference) whilst another 45 snails were also exposed to sediment and water collected from Lower Mguza Dam (polluted dam). Except for Fe in sediment and Pb in water, metal concentrations were statistically higher in sediment and water collected from Lower Mguza Dam. Lead, Cd and Zn were two times higher in tissues of snails exposed to Lower Mguza Dam elements. On one hand, superoxide dismutase (SOD), diphosphotriphosphodiaphorase (DTD) and catalase (CAT) activities were significantly lower whilst malondialdehyde (MDA) levels were significantly higher in tissues of snails exposed to Lower Mguza Dam sediment and water. On the other hand, selenium-dependent glutathione peroxidase (Se-GPX) activity was significantly elevated in tissues of snails exposed to Lower Mguza Dam sediment and water. Snails exposed to Lower Mguza Dam elements seem to have responded to pollution by increasing CAT and Se-GPX specific activity in an effort to detoxify peroxides produced as a result of metal induced oxidative stress.
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PMID:A comparison of metal levels and antioxidant enzymes in freshwater snails, Lymnaea natalensis, exposed to sediment and water collected from Wright Dam and Lower Mguza Dam, Bulawayo, Zimbabwe. 2081 7

Hepatic ischemia-reperfusion injury (IRI) limits access to transplantation. Heme oxygenase-1 (HO-1) is a powerful antioxidant enzyme which degrades free heme into biliverdin, free iron and carbon monoxide. HO-1 and its metabolites have the ability to modulate a wide variety of inflammatory disorders including hepatic IRI. Mechanisms of this protective effect include reduction of oxygen free radicals, alteration of macrophage and T cell phenotype. Further work is required to understand the physiological importance of the many actions of HO-1 identified experimentally, and to harness the protective effect of HO-1 for therapeutic potential.
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PMID:Heme oxygenase system in hepatic ischemia-reperfusion injury. 2118 21

Ovine malignant theileriosis is a fatal disease that is characterized by severe progressive anemia. In order to elucidate the underlying mechanisms involved in anemia, this study was designed to assess the antioxidant status and erythrocyte oxidative injuries in Iranian fat-tailed sheep that suffered from malignant theileriosis. The infected animals (infected group), composed of 50 Iranian sheep about 1-2 years old, naturally infected with Theileria sp., were divided into three subgroups according to parasitemia rates (<1%, 1-3%, 3-5%), and ten non-infected animals were also selected as the control group. Blood samples were taken and hematological parameters, the activities of antioxidant enzymes including superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase, erythrocyte osmotic fragility, and serum concentrations of some trace elements (copper, iron, zinc, manganese, and selenium), were measured. As an index of lipid peroxidation, the level of malondialdehyde (MDA) was also determined. According to the results, a significant decrease in red blood cell (RBC) count, packed cell volume, the activities of SOD, GPX, and catalase (P <0.001), and also serum concentrations of Cu, Zn, Mn, and Se (P < 0.05) were evident in the infected sheep. In contrast, significantly increased levels of MDA and erythrocyte osmotic fragility (P < 0.001) as well as serum concentration of iron (P < 0.05) were recorded in the infected animals. The significant decrease in antioxidant enzyme activities and substantial elevated levels of lipid peroxidation and erythrocyte osmotic fragility associated with the increase in parasitemia indicate increased exposure of RBCs to oxidative damage. Also, it appears that disturbed antioxidant defense mechanisms can promote the development of anemia in ovine theileriosis.
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PMID:Evaluation of erythrocyte antioxidant mechanisms: antioxidant enzymes, lipid peroxidation, and serum trace elements associated with progressive anemia in ovine malignant theileriosis. 2130 75

The present study attempts to assess the comparative effects of Bacopa monniera, (40 mg/kg body weight) and donepezil (2.5 mg/kg b. wt) on aluminum (100 mg / kg b. wt. of AlCl3) mediated oxidative damage in the cerebellum of aged rats (24 months) along with the associated dysfunctioning of neuromuscular coordination and motor activity. A significant decrease in the activities of antioxidant enzymes and increased total reacting oxygen species, lipid and protein peroxidation products observed in aluminum exposed rats. We observed that treatment with B. monniera extract restored the altered antioxidant enzyme activities more, when compared with donepezil. However, acetylcholinesterase showed similar effect both in donepezil and B. monniera treated groups. The content of aluminum was increased in all experimental groups, however, iron content was found increased in all groups except the B. monniera treated groups. Moreover, aluminum treated groups of rats exhibited significant changes in behavioral profiles but these changes were in both B. monniera and donepezil treated groups. The light microscopic and ultrastructural studies revealed damaged Purkinje's neurons and altered granular cell layer along with the increased accumulation of lipofuscin granules in aluminum treated animals. These changes were quite less pronounced in B. monniera group than that of donepezil and this may be due to the reduction of excess iron content by B. monniera. On the basis of our results it may be concluded that Al may be linked with cerebellar degeneration and neuromuscular disorders while Bacopa monniera extract helps in reversing these changes.
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PMID:Protective potential of Bacopa monniera (Brahmi) extract on aluminum induced cerebellar toxicity and associated neuromuscular status in aged rats. 2136 57

The release of H(2)O(2) from alveolar macrophages has been linked to the development of pulmonary fibrosis, but little is known about its source or mechanism of production. We found that alveolar macrophages from asbestosis patients spontaneously produce high levels of H(2)O(2) and have high expression of Cu,Zn-superoxide dismutase (SOD). Because Cu,Zn-SOD is found in the mitochondrial intermembrane space (IMS), we hypothesized that mitochondrial Cu,Zn-SOD-mediated H(2)O(2) generation contributed to pulmonary fibrosis. Asbestos-induced translocation of Cu,Zn-SOD to the IMS was unique to macrophages and dependent on functional mitochondrial respiration and the presence of at least one of the conserved cysteines required for disulfide bond formation. These conserved cysteine residues were also necessary for enzyme activation and H(2)O(2) generation. Cu,Zn-SOD-mediated H(2)O(2) generation was inhibited by knockdown of the iron-sulfur protein, Rieske, in complex III. The role of Cu,Zn-SOD was biologically relevant in that Cu,Zn-SOD(-/-) mice generated significantly less H(2)O(2) and had less oxidant stress in bronchoalveolar lavage fluid and lung parenchyma. Furthermore, Cu,Zn-SOD(-/-) mice did not develop pulmonary fibrosis, and knockdown of Cu,Zn-SOD in monocytes attenuated collagen I deposition by lung fibroblasts. Our findings demonstrate a novel mechanism for the pathogenesis of pulmonary fibrosis where the antioxidant enzyme Cu,Zn-SOD translocates to the mitochondrial IMS to increase H(2)O(2) generation in alveolar macrophages.
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PMID:Mitochondrial Cu,Zn-superoxide dismutase mediates pulmonary fibrosis by augmenting H2O2 generation. 2139 38


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