Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cellular protection against free radical reactions was measured in myocardium from ethanol-fed rats using ethanol administration in drinking water as a model of moderate alcohol intoxication. The activities of Cu,Zn-superoxide dismutase (SOD) and glutathione-S-transferase were higher in ethanol-fed rats than in controls, whereas Mn-SOD, catalase and glutathione peroxidase activities were not altered by ethanol treatment. Myocardial zinc was higher and selenium concentration lower in ethanol-fed rats than in controls. Ethanol consumption, which failed to modify the myocardial vitamin E level, did not result in increased lipid peroxidation, but decreased cytosolic and membraneous protein thiols.
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PMID:Effects of chronic ethanol administration on free radical defence in rat myocardium. 141 73

The antioxidant defenses of the liver, erythrocytes, blood plasma, and interscapular brown adipose tissue (IBAT) of male ground squirrels were compared with those of male rats kept under identical conditions and fed the same diet. Superoxide dismutase (SOD), ascorbate, vitamin E, catalase, glutathione, and enzymes of glutathione metabolism were measured. In general, antioxidant defenses in erythrocytes were lower in ground squirrels than in rats. The same was true in liver, except that catalase-specific activity was higher. In IBAT, ascorbate, vitamin E, catalase, and glutathione reductase were higher than in rat and more of the SOD activity present was cyanide-insensitive (MnSOD). It is suggested that IBAT in ground squirrels may need a relatively greater antioxidant defense because of its important role in thermogenesis, especially in reawakening from hibernation. No major differences in antioxidant defenses between male and female ground squirrels were observed, except that the SOD activity of IBAT was higher in females.
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PMID:Antioxidant defenses in the ground squirrel Citellus citellus. 1. A comparison with the rat. 229 34

Adriamycin (ADR) administration can result in cardiac toxicity. One suggested mechanism of damage is through increased lipid peroxidation. We have evaluated the biochemical response of mice to ADR treatment when fed Mn-sufficient, vitamin E-sufficient (+Mn, +E); Mn-sufficient, low vitamin-E (+Mn, -E); Mn-deficient, vitamin E-sufficient (-Mn, +E); or Mn-deficient, low vitamin-E (-Mn, -E) diets. Mice were injected i.p. with ADR (10 mg/kg bw) or saline (0.9% w/v). ADR injection resulted in a reduction of food intake by 2 days postinjection; by 5 days postinjection ADR-treated mice lost an average of 6.0 g. Heart Mn superoxide dismutase (SOD) activity of -Mn mice was 50% that of +Mn mice; ADR did not affect MnSOD activity. Lipid peroxidation was highest in the -Mn, -E mice, being 2-fold higher than that observed in +Mn, +E mice. ADR injection did not affect lipid peroxidation. An interaction between Fe and ADR treatment was apparent; ADR injected -Mn, -E mice had liver Fe concentrations which were twice that of the saline injected mice fed -Mn, -E diets. These data show that the antioxidant status of an animal may influence ADR toxicity.
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PMID:Influence of dietary manganese and vitamin E on adriamycin toxicity in mice. 395 76

During radiotherapy of thoracic tumors, the heart is often included in the primary treatment volume, and chronic impairment of myocardial function occurs. The cellular biomolecules are altered directly by radiation or damaged indirectly by free radical production. The purpose of this investigation was to evaluate the biochemical and functional responses of the rat heart to a single high dose of radiation. The effect of 20 Gy local X irradiation was determined in the heart of Wistar rats under general anesthesia. Mechanical performances were measured in vitro using an isolated perfused working heart model, and cardiac antioxidant defenses were also evaluated. Hearts were studied at 1 and 4 months after irradiation. This single dose of radiation induced a marked drop in the mechanical activity of the rat heart: aortic output was significantly reduced (18% less than control values) at 1 month postirradiation and remained depressed for the rest of the experimental period (21% less than control 4 months after treatment). This suggests the development of myocardial failure after irradiation. The decline of functional parameters was associated with changes in antioxidant defenses. The decrease in cardiac levels of vitamin E (-30%) was associated with an increase in the levels of Mn-SOD and glutathione peroxidase (+45.5% and +32%, respectively, at 4 months postirradiation). However, cardiac vitamin C and catalase levels remained constant. Since these antioxidant defenses were activated relatively long after irradiation, it is suggested that this was probably due to the production of free radical species associated with the development of inflammation.
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PMID:Effect of in vivo heart irradiation on the development of antioxidant defenses and cardiac functions in the rat. 756 73

A simple method in mice was established to screen anti-ischemic compounds. Thirteen times binding of rubber ring (1 x 1 mm, d = 42 mm) for 4.5 hrs, swelled the paws of 60% mice applied and 14 times binding swelled only of 5% mice. Critically reversible limit lay between these conditions. "All or none" rule dominated the paw swelling perhaps due to different endogenous anti-oxidants' levels of individual mice. Determination of paw reversibility at 90 min of recirculation, was proved to be suitable. Swollen paws at this time returned normal and the paws with no-reflow dropped out by muscle necrosis after several days. Intravenous (i.v.) bovine Cu, Zn-SOD and bacterial Mn-SOD (3-10 x 10(4) U/kg) or liposomal Cu, Zn-SOD (0.3-3 x 10(4) U/kg) were protective (35-50%) by 14 times binding. Allopurinol (10-100 mg/kg) and D-mannitol (3-30 mg/kg) was effective (25-55%). Catalase (i.v., up to 10(5) U/kg) showed little protection, but local injection of 100 U/kg resulted in 50% protection. Glutathione (30 mg/kg) was suppressive only by local injection suggesting the importance of administration route. Desferal, heparin and nitric oxide synthesis inhibitor showed some protection, but indomethacin, mepyramine, ascorbate, vitamin E and dexamethasone were without effect. Excess dosing of all anti-oxidants tested, dramatically decreased their effects demanding caution for therapeutic trials.
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PMID:Superoxide dismutases and anti-oxidants protected mice from no-reflow and necrotic damage induced by ischemia. 831 25

Free radical production and lipid peroxidation are potentially important mediators in testicular physiology and toxicology. The cytochrome P450 enzymes of the steroidogenic pathway are known to produce free radicals. The present study was conducted to elucidate in vivo the gonadotropin regulation of free radical-mediated lipid peroxidation and the antioxidative defense system in the rat testis. GnRH antagonist (Org 30276; 1 mg/kg BW) and testosterone [40-mm SILASTIC brand (Dow-Corning) capsules] treatments were used to suppress serum gonadotropin levels. As expected, serum LH decreased to a very low level, whereas serum FSH decreased only slightly. Testosterone treatment for 8 days decreased the levels of the peroxide-metabolizing enzymes, catalase, glutathione peroxidase (GSH-Px), and glutathione transferase (-44%, -24%, and -31%, respectively; P < 0.01 for all). These changes predominately reflect the interstitial tissue, in which catalase and GSH-Px activities were much higher than in the seminiferous tubules. Testicular CuZn or Mn superoxide dismutase activities, which were high in the seminiferous tubules, were not affected by gonadotropin suppression. The total peroxyl radical-trapping capacity of the testis, or its components, vitamin E and ubiquinol 9, were not affected either. Lipid peroxidation was decreased after 8-day treatment, as detected by diminished formation of conjugated dienes and fluorescent chromolipids (-30% and -19%, respectively; P < 0.05 for both). Similar results of decreasing catalase and GSH-Px activities were found after gonadotropin suppression with GnRH antagonist treatment for 2 days or testosterone treatment for 5 days. Substitution with hCG, alone or in combination with recombinant human FSH, reversed the changes in enzyme activities, whereas FSH alone had no effect. After 5-day testosterone treatment, catalase messenger RNA expression was studied by Northern hybridization, and it was observed to parallel the changes in enzyme activity. The site of free radical production was studied by separating interstitial tissue and seminiferous tubules 5 h after hCG injection. GSH-Px was induced by hCG only in the interstitial tissue (+28%; P< 0.01), supporting the hypothesis of free radical production during steroidogenesis. Aminoglutethimide, an inhibitor of the P450 cholesterol side-chain cleavage enzyme, induced extensive lipid peroxidation in the testis. Presumably, aminoglutethimide leads to leakage of free radicals from the P450 enzyme when substrate oxygenation is prevented. In conclusion, the present study suggests that physiological LH action in the rat testis causes lipid peroxidation and maintains high activities of peroxide-metabolizing enzymes in the interstitial tissue.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Induction of lipid peroxidation during steroidogenesis in the rat testis. 853

In this study, the activities of major enzymes participating in free radical metabolism (xanthine oxidase, XO; Cu,Zn and Mn superoxide dismutases, SOD; glutathione peroxidase, GSH-Px; catalase, CAT) were measured in kidney tissues from guinea pigs treated with gentamicin alone (200 mg/kg/day), gentamicin plus vitamin C (600 mg/kg/day), gentamicin plus vitamin E (400 mg/kg/day), and gentamicin plus vitamins C and E together for 10 days, and from animals treated with physiological saline solution alone during this period. We found no significant differences between control and gentamicin groups with respect to XO and Cu,Zn-SOD activities. However, the activities of Mn-SOD, GSH-Px, and CAT were found to be significantly depressed in the gentamicin-treated group relative to controls. In the gentamicin plus vitamin C group, the renal tissue Mn-SOD activity was found to be higher as compared with control and gentamicin groups. In this group, XO, GSH-Px and CAT activities were also higher than in the gentamicin-treated group, but no statistically significant differences existed between the values of this group and controls. Similar results were also observed in the gentamicin plus vitamin E group for Mn-SOD, GSH-Px, CAT, and XO. In this group, the Cu,Zn-SOD activity was found to be decreased as compared with control and gentamicin groups. In the gentamicin plus vitamins C and E group, the Cu,Zn-SOD activity was found to be decreased, the XO activity to be unchanged, and Mn-SOD, GSH-Px, and CAT activities to be increased as compared with the gentamicin and control groups. The results suggest that the enzymatic antioxidant defense system was significantly disturbed because of the suppressed activities of Mn-SOD, GSH-Px, and CAT in the kidney tissues from animals treated with gentamicin. However, vitamins C and E given concurrently with gentamicin completely abrogated this enzymatic suppression.
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PMID:Reduced enzymatic antioxidant defense mechanism in kidney tissues from gentamicin-treated guinea pigs: effects of vitamins E and C. 868 38

The cellular function of the prion protein (PrPc), a cell surface glycoprotein expressed in neurones and astrocytes, has not been elucidated. Cell culture experiments reveal that cerebellar cells lacking PrPc are more sensitive to oxidative stress and undergo cell death more readily than wild-type cells. This effect is reversible by treatment with vitamin E. In vivo studies show that the activity of Cu/Zn superoxide dismutase is reduced in Prnp gene-ablated (Prnp0/0) mice. Constitutively high Mn superoxide dismutase activity in these animals may compensate for this loss of responsiveness to oxidative stress. These findings suggest that PrPc may influence the activity of Cu/Zn superoxide dismutase and may be important for cellular resistance to oxidative stress.
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PMID:Prion protein-deficient cells show altered response to oxidative stress due to decreased SOD-1 activity. 922 43

Vascular smooth muscle cell (VSMC) dysfunction plays a role in diabetic macrovasculopathy and this may include abnormalities in growth characteristics and the extracellular matrix. As the actual mechanisms by which glucose induces VSMC dysfunction remain unclear, the aim of this study was to assess the potential role of glucose-induced oxidative stress. Porcine aortic VSMCs were cultured for 10 days in either 5 mmol/l normal glucose or 25 mmol/l D-glucose (high glucose). There was evidence of oxidative stress as indicated by a 50% increase in intracellular malondialdehyde (p < 0.05), increased mRNA expression of CuZn superoxide dismutase and Mn superoxide dismutase (by 51% and 37% respectively, p < 0.01) and a 50% decrease in glutathione in 25 mmol/l D-glucose (p < 0.001). Growth was increased by 25.0% (p < 0.01). mRNA expression of extracellular matrix proteins (collagens I, III, IV and fibronectin) was not altered by high glucose in these experimental conditions. Repletion of glutathione with N-acetyl L-cysteine (1 mmol/l) in VSMC grown in high glucose was associated with reduction in malondialdehyde and restored growth to that of normal glucose. The water soluble analogue of vitamin E, Trolox (200 mumol/l), reduced malondialdehyde concentrations, but had no effect on glutathione depletion or the increased growth rate seen with high glucose. The addition of buthionine sulphoximine (10 mumol/l) to VSMC cultured in normal glucose reduced glutathione, increased malondialdehyde and increased growth to a similar extent as that found in high glucose alone. These results suggest that thiol status, rather than lipid peroxides, is a key factor in modulating VSMC growth and that mRNA expression of extracellular matrix proteins is not increased in VSMC under conditions of glucose-induced oxidative stress.
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PMID:The effects of glucose-induced oxidative stress on growth and extracellular matrix gene expression of vascular smooth muscle cells. 979 10

Previous experimental data indicate the involvement of Ca(2+)-related excitotoxic processes, possibly mediated by N-Methyl-D-Aspartate (NMDA) receptors, in beta-amyloid (beta A) neurotoxicity. On the other hand, other lines of evidence support the view that free radical generation is a critical step in the beta A-induced neurodegenerative cascade. In the present study, therefore, a neuroprotective strategy was applied to explore the contributions of each of these pathways in beta A toxicity. beta A(1-42) was injected into the magnocellular nucleus basalis of rats, while neuroprotection was achieved by either single or combined administration of the NMDA receptor antagonist MK-801 (2.5 mg/kg) and/or a vitamin E and C complex (150 mg/kg). The degree of neurodegeneration was determined by testing the animals in consecutive series of behavioral tasks, including elevated plus maze, passive avoidance learning, small open-field and open-field paradigms, followed by acetylcholinesterase (AChE), choline-acetyltransferase (ChAT), and superoxide dismutase (SOD) biochemistry. beta A injected in the nucleus basalis elicited significant anxiety in the elevated plus maze, derangement of passive avoidance learning, and altered spontaneous behaviors in both open-field tasks. A significant decrease in both AChE and ChAT accompanied by a similar decrement of MnSOD, but not of Cu/ZnSOD provided neurochemical substrates for the behavioral changes. Each of the single drug administrations protected against the neurotoxic events, whereas the combined treatment failed to ameliorate beta A toxicity.
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PMID:N-Methyl-D-aspartate receptor antagonist MK-801 and radical scavengers protect cholinergic nucleus basalis neurons against beta-amyloid neurotoxicity. 1034 26


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