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)

The effect of sodium metavanadate (NaVO3) consumption on trace element metabolism, components of the antioxidant defense system and lipid oxidative damage were studied in control (CON) and streptozotocin-induced diabetic (DIAB) rats. Ten days after injection, CON and DIAB rats received either 0 mM NaVO3/80 mM NaCl (0 group) or 1.2 mM NaVO3/80 mM NaCl (1.2V group) in their drinking water. DIAB groups had higher food and fluid intakes than the CON groups; vanadium (V) groups had lower food and fluid intakes than the saline groups. Vanadium therapy lowered plasma glucose concentrations of DIAB rats. The following parameters were similar among the groups: plasma Zn, Cu and Fe concentrations, plasma ceruloplasmin activity, liver Zn, Cu, Mn and Fe concentrations, kidney Mn and Fe concentrations, liver non-Se-dependent glutathione peroxidase (GSH-Px), glutathione reductase (GSH-Red) and Mn-SOD activities, liver reduced glutathione (GSH) and oxidized glutathione (GSSG) concentrations and kidney non-Se-dependent GSH-Px activity. Kidney Zn and Cu concentrations were higher in DIAB rats than in CON rats. The CON-1.2V and DIAB-1.2V groups had V accumulation in the liver and kidney. Liver CuZn-SOD and Se-dependent GSH-Px and kidney CuZn-SOD and GSH-Red activities were lower in DIAB rats compared to CON rats; kidney Mn-SOD and kidney Se-dependent GSH-Px activities were higher in DIAB rats than CON rats. Vanadium treatment did not cause significant alterations in the antioxidant defense system; however, tissue vanadium concentrations were positively correlated to TBARS production. These results show that diabetes caused significant alterations in the antioxidant defense system and that V therapy was associated with a marked deterioration in health of both control and diabetic rats.
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PMID:Vanadium treatment of diabetic Sprague-Dawley rats results in tissue vanadium accumulation and pro-oxidant effects. 824 40

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

Saccharomyces cerevisiae aBR10 cells are able to develop resistance to lethal ethanol concentrations (14%, v/v), by preexposure to a sublethal heat shock (37 degrees C) or ethanol stress (8%, v/v). Heat shock and 8% ethanol stress had no effect on the concentrations of glutathione [reduced (GSH) and oxidized (GSSG) forms] and on glutathione reductase and CuZn superoxide dismutase (SOD) activities, suggesting that the development of resistance to lethal ethanol concentrations is independent of these antioxidant defenses. In fact, a S. cerevisiae mutant, deficient in CuZnSOD, had an even higher ethanol tolerance, compared to the wild-type strain, and this mutation did not impair a further acquisition of ethanol tolerance. In contrast to CuZnSOD, the MnSOD activity seems to play a more important role in ethanol resistance. The MnSOD activity of the S. cerevisiae aBR10 cells increased upon exposure to heat shock or 8% ethanol. The higher tolerance to 14% ethanol in CuZnSOD deficient cells was also associated to a higher MnSOD activity, as compared to the aBR10 cells; this activity decreased during both stress pretreatments (while still higher than that observed in the wild-type strain). The results obtained suggest that maximum ethanol tolerance is attained with a MnSOD activity close to 1.0 U/mg protein. On either side of this value, the increased sensitivity of S. cerevisiae cells to 14% ethanol might be due to an inability to prevent either superoxide radical- or hydrogen peroxide-induced damages, respectively. These results are supported by the fact that a MnSOD deficiency renders yeast cells more ethanol sensitive.
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PMID:Acquisition of ethanol tolerance in Saccharomyces cerevisiae: the key role of the mitochondrial superoxide dismutase. 843 41

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

Cu/Zn-superoxide dismutase (SOD)-accelerated oxidation of the benzene metabolite 1,4-hydroquinone (HQ) results in the enhanced formation of semiquinone anion radicals, electrophilic 1,4-benzoquinone (BQ), and H202. We selected bone marrow stromal cells and phiX-174 double stranded plasmid DNA as model systems to investigate the cytotoxicity and DNA cleaving activity of the Cu/Zn-SOD-mediated activation of HQ. The addition of either Cu/Zn-SOD or Min-SOD to the primary bone marrow stromal cell cultures significantly enhanced HQ-induced cytotoxicity, which could be completely prevented by adding reduced glutathione (GSH) or dithiothreitol but not be adding catalase. Incubation of the plasmid DNA with the HQ/Cu/Zn-SOD system resulted in the induction of single- as well as double-strand breaks, which could be inhibited by catalase and the Cu(I) chelators, bathocuproinedisulfonic acid (BCS) and GSH. Although Mn-SOD could enhance HQ-induced cytotoxicity to stromal cells, the activation of HQ by Mn-SOD did not contribute to the induction of DNA strand breaks. Similar to the HQ/Cu(II) and H202/Cu(II) systems, the DNA strand breaks mediated by HQ/Cu/Zn-SOD could not be effectively inhibited by the hydroxyl radical scavengers, including dimethylsulfoxide, mannitol, and 5,5-dimethyl-1-pyrroline N-oxide, but could be protected by sodium azide. Low-temperature electron spin resonance experiments showed that incubation of Cu/Znu-SOD with HQ resulted in the release of copper from the Cu/Zn-SOD, which could be prevented by catalase. Alpha-(4-Pyridyl-1-oxide)-N-tert-butylnitrone (POBN)/spin-trapping studies demonstrated that the interaction of HQ with Cu/Zn-SOD, but not with Mn-SOD, resulted in the significant formation of POBN-CH3 adduct in the presence of dimethylsulfoxide, suggesting the production of hydroxyl radical or its equivalent from this enzyme/xenobiotic interaction. The formation of the POBN-CH3 adduct from the HQ/Cu/Zn-SOD could be inhibited by catalase, BCS or GSH, indicating the important role for H202 and Cu(I) in the production of reactive oxygen species. Addition of human myeloperoxidase to the HQ/Cu/Zn-SOD synergistically enhanced the formation of BQ from HQ. This enhancement could be abolished by catalase. Taken together, these results demonstrate that activation of HQ by either Cu/Zn-SOD or Mn-SOD results in cytotoxicity to primary bone marrow stromal cells through the formation of electrophilic BQ. Interaction of HQ with Cu/Zn-SOD causes oxidative damage to Cu/Zn-SOD, leading to the release of copper from the enzyme. The further reaction between the released copper and H202 generates reactive oxygen species that participate in the induction of strand breaks in plasmid DNA. The H202 generated from the Cu/Zn-SOD-accelerated oxidation of HQ can also be utilized by myeloperoxidase resulting in additional conversion of HQ to BQ.
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PMID:Role of Cu/Zn-superoxide dismutase in xenobiotic activation. II. Biological effects resulting from the Cu/Zn-superoxide dismutase-accelerated oxidation of the benzene metabolite 1,4-hydroquinone. 864 80

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

1. The present study was undertaken to investigate the effects of hypobaric hypoxia, equivalent to an altitude of 5500 m, on antioxidant enzymes in rats. 2. Malondialdehyde levels in serum, heart, lung, liver and kidney of hypobaric-hypoxic rats were all significantly higher than in control rats by day 21 of exposure (P < 0.05), indicating increased oxidative stress. 3. Superoxide dismutase (SOD) catalyses the conversion of the superoxide anion to H2O2 and O2. The concentration of immunoreactive Mn-SOD in the serum of hypobaric-hypoxic rats was raised significantly from day 5 onwards, whereas in liver and lung, it had decreased significantly by day 21 (P < 0.05). 4. Glutathione peroxidase (GSH-Px) catalyses H2O2 and certain lipid peroxides. By day 21, GSH-Px activity had increased significantly in the heart and lungs, but decreased significantly in the liver (P < 0.05). 5. Catalase catalyses H2O2. Catalase activity in the liver and kidney of hypobaric-hypoxic rats was significantly decreased on day 1 (P < 0.05) though levels then recovered. 6. Mn-SOD mRNA in the liver of hypobaric-hypoxic rats was induced during the experiment, the effect being exceptionally marked, especially during the first 3 days of exposure to hypobaric hypoxia. 7. These results suggest that the liver may be more vulnerable than the other organs tested to oxidative stress under hypobaric hypoxia.
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PMID:Effects of hypobaric hypoxia on antioxidant enzymes in rats. 878 50

Seventy male factory workers were studied. The lead concentrations in their blood (Pb-B) were 16.55 +/- 11.53 micrograms/100 ml (range 1.5 to 50.2 micrograms/100 ml). The subjects were divided into three groups according to Pb-B (in microgram/100 ml): group A, Pb-B < or = 10 (n = 22); group B, 10 < Pb-B < or = 20 (n = 30); group C, Pb-B > 20 (n = 18). The mean +/- S.D. in each group was 5.57 +/- 2.53, 15.02 +/- 2.75, and 32.52 +/- 9.49 micrograms/100 ml, respectively. Pb in plasma was 0.011 +/- 0.010, 0.017 +/- 0.033, and 0.021 +/- 0.021 microgram/liter, and Pb in the RBC was 0.281 +/- 0.246, 0.701 +/- 0.325, and 1.626 +/- 0.861 micrograms/g Hb, respectively. In addition to Pb concentration, the concentrations of 34 elements in the plasma or in the RBC were determined. Se concentrations in RBC in each group were 0.618 +/- 0.139, 0.670 +/- 0.207, and 0.728 +/- 0.200 microgram/g Hb, and the mean values were significantly different between groups A and C (p < 0.05). For Se concentration in plasma, the mean +/- S.D. in each group was 0.132 +/- 0.035, 0.130 +/- 0.031, and 0.126 +/- 0.021 microgram/ml, respectively, and there was no significant difference between groups. On the other hand, when the activities of total SOD, Mn-SOD, Cu, Zn-SOD, and catalase in the plasma and the activities of GSH-Px both in the plasma and in the RBC were assayed, some differences were found. The activities in GSH-Px in RBC were 17.19 +/- 5.03, 17.59 +/- 3.95, and 15.25 +/- 3.18 mumol/g Hb/min, and those in plasma were 0.069 +/- 0.032, 0.081 +/- 0.023, and 0.080 +/- 0.028 mumol/ml/min. In group C, GSH-Px activity was lower in the RBC and higher in the plasma than those in group A, and it was observed that the Se concentration was higher in RBC, and that there was no remarkable change in the plasma. Catalase activity in group C was 3.58 +/- 0.81 mgH2O2/ml/30 min, which was significantly higher than that in group A (2.81 +/- 0.90 mgH2O2/ml/30 min). Further investigation is necessary in order to explain the above results. The regular indices used for evaluating lead exposure, showed significant correlations with Pb-B: r = -0.786 vs delta-Aminolevulinic acid (ALA) dehydratase activity in blood, r = 0.927 vs. inhibition rate, and r = 0.339 vs. ALA in urine.
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PMID:Indices of lead-exposure in blood and urine of lead-exposed workers and concentrations of major and trace elements and activities of SOD, GSH-Px and catalase in their blood. 884 89

The activities of antioxidant enzymes i.e. Cu, Zn-SOD, Mn-SOD, CAT, and GSH-Px in the normal brain and brain tumors, as well as the two varieties of SOD in the mitochondria were examined and correlated to the histopathological diagnosis and the degree of malignancy of tumors. It was found that these scavenging enzymes of oxygen free radicals were expressed with great regularity in brain tumors. Both Cu, Zn-SOD and Mn-SOD were decreased in descending order in meningiomas, low grade astrocytomas, high grade astrocytomas and medulloblastomas. Furthermore, the reduction of Mn-SOD in mitochondria was proportionate to that of the whole tissues. While in contrast to the SODs, the CAT levels were significantly increased in ascending order in high grade astrocytomas, low grade astrocytomas and meningiomas. GSH-Px increased in meningiomas but not in gliomas.
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PMID:Study of the antioxidant enzymes in human brain tumors. 885 16

Reactive oxygen species are important mediators of cellular damage during endotoxic shock. In order to investigate the hepatic response to the oxidative stress induced by endotoxin, hepatic and plasma glutathione (total, GSH and GSSG), GSSG/GSH ratio as well as Mn-superoxide dismutase and catalase activities were determined during the acute and recovery phases of reversible endotoxic shock in the rat. A significant increase in liver and plasma total glutathione content was observed 5 h after endotoxin treatment (acute phase), followed by a diminution of these parameters below control values at 48 h (recovery phase). The significant increases of GSSG levels and GSSG/GSH ratio are indicative of oxidative stress occurring during the acute phase. Liver Mn-SOD activity showed a similar time dependency as the GSSG/GSH ratio; however, a marked decrease in the liver catalase activity was observed during the process. These results indicate the participation of liver glutathione in the response to endotoxin and the possible use of plasma glutathione levels and GSSG/GSH ratio as indicators of the acute phase during the endotoxic process.
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PMID:Hepatic response to the oxidative stress induced by E. coli endotoxin: glutathione as an index of the acute phase during the endotoxic shock. 885 61


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