UMLS:C0022116 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cu,Zn-superoxide dismutase is an endogenous scavanger of superoxide radicals (O(2)(*-)) which also induce the synthesis of this enzyme. Ceruloplasmin is an antioxidant and acute-phase reactant. Changes in the synthesis of both enzymes are related to the metabolism of copper and zinc. Concentrations of copper and zinc were previously found to be increased in the serum and arterial wall of atherosclerotic subjects. The aim of this study was to investigate the Cu,Zn-superoxide dismutase activity in erythrocytes and ceruloplasmin activity in serum, and to measure serum concentrations of copper, zinc, and malonyldialdehyde in patients with moderate and critical chronic ischemia of the lower limbs. A group of 26 patients with chronic arterial occlusion of the lower limbs was divided into two groups depending on the degree of ischemia: moderate and critical. Cu,Zn-superoxide dismutase activity in erythrocytes was measured using the RANSOD kit, the serum ceruloplasmin oxidase activity was determined with o-dianisidine as a substrate. Copper and zinc concentrations in serum were determined by atomic absorption spectrometry. There was an increase in the ceruloplasmin activity and serum copper concentration in critical ischemia (194.4+/-51.94 U/l and 23.5+/-4.2 micromol/l, respectively) compared with moderate ischemia (139.1+/-34.9 U/l and 18.5+/-2.0 micromol/l, respectively). The Cu,Zn-superoxide dismutase activity in erythrocytes was higher in moderate ischemia (2,657+/-1,564 U/g hemoglobin) than in controls (1,205+/- 353 U/g hemoglobin), but not different from critical ischemia. There was a negative correlation for Cu,Zn-superoxide dismutase and ceruloplasmin (r=-0.60, P</=0.05) in critical ischemia.
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PMID:Activities of copper,zinc-superoxide dismutase in erythrocytes and ceruloplasmin in serum in chronic ischemia of lower limbs. 1043 63

This study aimed to examine whether an elevated activity of heme oxygenase (HO)-1 in the tissue attenuates endothelial cell-leukocyte interactions microvessels in vivo. When rats were pretreated with an intraperitoneal injection of hemin, an HO-1 inducer, mesenteric tissues, including their microvessels, displayed a marked induction of HO-1 concurrent with an increase in plasma concentrations of bilirubin-IXalpha, the product of HO-catalyzed degradation of protoheme IX. In these rats, oxidative stress such as superfusion with H(2)O(2) and ischemia-reperfusion of the tissues neither induced rolling nor exhibited adherent responses of leukocytes in venules. In contrast, the oxidative stresses evoked marked rolling and adhesion of leukocytes in the control rats without HO-1 induction. The HO-1 induction also downregulated leukocyte adhesion elicited by other pro-oxidant stimuli such as N(omega)-nitro-L-arginine methyl ester. The decreases in the oxidant-elicited leukocyte adhesive responses under HO-1-inducing conditions were restored by perfusion with zinc protoporphyrin-IX, an HO inhibitor, but not with copper protoporphyrin-IX, which did not inhibit the enzyme. Furthermore, the effects of zinc protoporphyrin-IX were repressed by superfusion with bilirubin or biliverdin at the micromolar level, but not by the same concentration of carbon monoxide, another product of HO. These results indicate that induction of the HO-1 activity serves as a potential stratagem to prevent oxidant-induced microvascular leukocyte adhesion through the action of bilirubin, a product of HO reaction.
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PMID:Induction of heme oxygenase-1 suppresses venular leukocyte adhesion elicited by oxidative stress: role of bilirubin generated by the enzyme. 1052 Dec 39

Formation of oxygen free radicals during heart transplantation seems to be related to the alterations occurring during ischemia and reperfusion and could explain the short preservation time of donor hearts. The aim of our study was (a) to analyze the protective effects of pyruvate during cold cardioplegia and ischemia/reperfusion sequence, and (b) to investigate in vitro the radical scavenging properties of this compound. After 30 min of perfusion, isolated working rat hearts were arrested by cardioplegic solution, stored 4 h in B21 solutions at 4 degrees C, and reperfused with Krebs-Henseleit buffer for 45 min. Pyruvate (2 mM) was added to Krebs-Henseleit, cardioplegic, and storage solutions, and functional parameters were recorded throughout the experiments. In a second part, control hearts and hearts treated with pyruvate were cannulated via the aorta and perfused for 30 min by the Langendorff method, arrested by cardioplegic solution, stored 4 h in B21 solutions at 4 degrees C, and reperfused for 45 min by the Langendorff method. Malonedialdehyde and alpha-tocopherol levels were determined on heart homogenate. In situ detection of apoptotic cells also was performed on tissue samples (left ventricle) at the end of the ischemia/reperfusion sequence. To demonstrate in vitro the antioxidant effects of pyruvate, we monitored (a) its hydroxyl radical scavenging properties by using electron paramagnetic resonance (EPR) spectroscopy, and (b) the decrease of fluorescence of allophycocyanin, in the presence of a Fenton system (H2O2/Cu2+). Ischemia for 4 h, followed by myocardial reperfusion, resulted in substantially reduced mechanical function. Hearts subjected to this ischemia and pretreated with pyruvate showed a significant improvement in the function recovery. After the ischemia/reperfusion protocol, no significant decrease of malonedialdehyde levels was shown on hearts treated with pyruvate. However, alpha-tocopherol levels were higher in the pyruvate group compared with the control group. At the end of the reperfusion period, levels of apoptotic cells were significantly lower in hearts treated with pyruvate compared with control hearts. EPR studies showed that pyruvate was an efficient hydroxyl scavenger, with a median inhibitory concentration (IC50) of 8 mM. The allophycocyanin assay also showed a dose-dependent effect of pyruvate against hydroxyl radicals. In conclusion, these findings showed that pyruvate could prevent reperfusion injuries in the isolated heart, probably by its antioxidative properties. The application of pyruvate may contribute to the preservation of hearts for organ transplantation.
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PMID:Antioxidative properties of pyruvate and protection of the ischemic rat heart during cardioplegia. 1054 80

The authors show that the inhibitor of the succinate dehydrogenase, 3-nitroproprionic acid (3-NPA), which in high doses and with chronic administration is a neurotoxin, can induce profound tolerance to focal cerebral ischemia in the rat when administered in a single dose (20 mg/kg) 3 days before ischemia. Infarcts were approximately 70% and 35% smaller in the 3-NPA preconditioned groups of permanent and transient focal cerebral ischemia, respectively. This regimen of 3-NPA preconditioning neither induced necrosis, apoptosis, or any other histologically detectable damage to the brain, nor did it affect behavior of the animals. 3-NPA led to an immediate (1-hour) and long-lasting (3-day) decrease in succinate dehydrogenase activity (30% reduction) throughout the brain, whereas only a short metabolic impairment occurred (ATP decrease of 35% within 30 minutes, recovery within 2 hours). The authors found that 3-NPA induces a burst of reactive oxygen species and the free radical scavenger dimethylthiourea, when administered shortly before the 3-NPA stimulus, completely blocked preconditioning. Inhibition of protein synthesis with cycloheximide given at the time of 3-NPA administration completely inhibited preconditioning. The authors were unsuccessful in showing upregulation of mRNA for the manganese superoxide dismutase, and did not detect increased activities of the copper-zinc and manganese superoxide dismutases, prototypical oxygen free radicals scavenging enzymes, after 3-NPA preconditioning. The authors conclude that it is possible to pharmacologically precondition the brain against focal cerebral ischemia, a strategy that may in principal have clinical relevance. The data show the relevance of protein synthesis for tolerance, and suggests that oxygen free radicals may be critical signals in preconditioning.
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PMID:Respiratory chain inhibition induces tolerance to focal cerebral ischemia. 1056 69

Patients with peripheral vascular disease (Fontaine stage II) are characterized by ischemia of the lower extremities, atherosclerosis and alteration of blood coagulation and fibrinolysis. A randomized, two-period, crossover design was used to compare the effects of extra-virgin (VO) and refined olive (RO) oils on plasma lipids and lipoprotein composition and LDL oxidation susceptibility in free-living men with peripheral vascular disease. The oils differed in their antioxidant profile (alpha-tocopherol: 300 vs. 200 mg/kg; phenolic compounds 800 vs. 60) and concentration but not in their fatty acid composition. Subjects were randomly assigned to two groups. The first group (n = 12) received VO with which to freely cook all meals for 3 mo, followed by a 3-mo wash-out period; they then received RO for the final 3 mo. The second group (n = 12) consumed the oils in the opposite order. Energy, fat, polyunsaturated fatty acids (PUFA) and alpha-tocopherol intakes were not different when patients consumed the two oils. Profiles of the major fatty acids in plasma and LDL were not different after consumption of VO and RO. The slope of the line for LDL oxidation vs. the line for copper concentration was significantly higher after the intake of RO than after the intake of VO. Total LDL taken up by macrophages was significantly greater when the men consumed RO rather than VO. We suggest that antioxidants present in VO may protect LDL against oxidation more than does RO in men with peripheral vascular disease.
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PMID:Extra-virgin olive oil increases the resistance of LDL to oxidation more than refined olive oil in free-living men with peripheral vascular disease. 1057 46

The antioxidant function of metallothionein (MT) was first suggested in the early 1980s. Studies in vitro have revealed that MT reacts directly with reactive oxygen species, including superoxide and hydroxyl radicals and hydrogen peroxide. These reactions have never been demonstrated in intact animal studies. Nevertheless, both pharmacologic and genetic studies have shown that MT functions in protection against oxidative injury in vivo. In particular, the antioxidant function of MT in the heart has been explored extensively. The data gathered from recent studies using a cardiac-specific, MT-overexpressing transgenic mouse model have provided direct evidence to support this physiological role of MT. Under acute and chronic oxidative stress conditions such as treatment with doxorubicin, ischemia-reperfusion, and dietary copper restriction, MT-overexpressing transgenic mouse hearts displayed a marked resistance to the injurious consequences, including biochemical, pathological, and functional alterations. This protective action of MT correlates with its inhibition of reactive oxygen species-induced lipid peroxidation. A critical elucidation of the mechanism of action of MT as an antioxidant in vivo remains to be achieved. However, the combination of recent understanding of the zinc cluster structure of MT and novel molecular genetic approaches has provided the basis for further advancement in this field.
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PMID:The antioxidant function of metallothionein in the heart. 1060 85

Release of mitochondrial cytochrome c into the cytosol is a critical step in apoptosis. We have reported that early release of cytochrome c in vivo occurs after permanent focal cerebral ischemia (FCI) and is mediated by the mitochondrial antioxidant manganese superoxide dismutase (SOD). However, the role of reactive oxygen species produced after ischemia-reperfusion in the mitochondrial apoptosis process is still unknown, although overexpression of copper/zinc-SOD (SOD1), a cytosolic isoenzyme, protects against ischemia-reperfusion. We now hypothesize that the overexpression of SOD1 also prevents apoptosis after FCI. To address this issue, we examined the subcellular distribution of the cytochrome c protein in both wild-type mice and in SOD1 transgenic (Tg) mice after transient FCI. Cytosolic cytochrome c was detected as early as 2 hr after reperfusion, and correspondingly, mitochondrial cytochrome c was significantly reduced after FCI. Cytosolic cytochrome c was significantly lower in the SOD1 Tg mice compared with wild types 2 (p < 0.0001) and 4 (p < 0.05) hr after FCI. Apaf-1, which interacts with cytochrome c and activates caspases, was constitutively expressed in both groups of animals, with no alteration after FCI. Double staining with cytochrome c immunohistochemistry and terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling showed a spatial relationship between cytosolic cytochrome c expression and DNA fragmentation. A significant amount of DNA laddering was detected 24 hr after ischemia and was reduced in SOD1 Tg mice. These data suggest that SOD1 blocks cytosolic release of cytochrome c and could thereby reduce apoptosis after transient FCI.
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PMID:The cytosolic antioxidant copper/zinc-superoxide dismutase prevents the early release of mitochondrial cytochrome c in ischemic brain after transient focal cerebral ischemia in mice. 1075 33

The relationships among concentrations of copper and zinc, the oxidase activity of ceruloplasmin (Cp) in serum, and Cu,Zn-SOD (superoxide dismutase) activity in erythrocytes were investigated in men with atherosclerosis obliterans (AO) and a control group. The oxidase activity of Cp was measured with o-dianisidine dihydrochloride as a substrate, and Cu,Zn-SOD activity in erythrocytes by using the RANSOD kit. The lipid profile and uric acid concentration were determined in AO and control groups. The results showed higher copper and zinc concentrations in serum in the AO group (20.0+/-3.5 and 18.0+/-3.2 micromol/L, respectively) in comparison with the control group (15.6+/-2.3 and 14.7+/-1.9 micromol/L). The Cp activity in serum was higher in the AO group (174.2+/-61.8 U/L) than in the control group (93.7+/-33.9 U/L), and a significant difference was found in the activity of Cu,Zn-SOD in erythrocytes (2389+/-1396 and 1245+/-365 U/g Hb, respectively) between both groups. The activity of Cu,Zn-SOD was positively correlated with copper in the control group (r=0.73), but not in AO, and negatively with uric acid concentration (r= -0.63) in the AO group. The oxidase activity of Cp was correlated with copper, but not zinc, in AO and control groups (r> or =0.65). Negative correlation coefficients were calculated for uric acid and copper and zinc concentrations in the AO group (-r > or = 0.61). Increased copper concentrations and oxidase activity of Cp in serum in AO and the activity of Cu,Zn-SOD in erythrocytes could result from atherosclerotic disease, accompanied by chronic ischemia of a lower limb. These results suggest also that relationship between copper concentration and Cu,Zn-SOD activity in erythrocytes found in the serum of healthy subjects may be disturbed in pathologic conditions.
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PMID:Copper and zinc concentrations and the activities of ceruloplasmin and superoxide dismutase in atherosclerosis obliterans. 1094 69

Spreading depression (SD) is a wave of sustained depolarization challenging the energy metabolism of cells without causing irreversible damage. SD is a major mechanism of gene induction that takes place in cortical injury, including ischemia. We studied the role of oxygen radicals in SD-induced c-fos and cyclooxygenase-2 (COX-2) induction using transgenic (Tg) mice that overexpress copper/zinc-superoxide dismutase (SOD1). The frequency, amplitude and duration of SD waves were similar in the Tg mice and wild-type littermates. c-fos and COX-2 mRNAs were strongly induced 1 and 4 h after SD. The induction of both genes was slightly but significantly less at 4 h in the Tg mice. The results indicate that even a mild, noninjurious metabolic stimulation increases the concentration of oxygen radicals to the level that contributes to gene expression.
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PMID:Spreading depression-induced expression of c-fos and cyclooxygenase-2 in transgenic mice that overexpress human copper/zinc-superoxide dismutase. 1097 46

In this study, we investigated the impact of ischemia-reperfusion on antioxidant enzyme activities and trace element concentrations. For this purpose, ischemia was initiated by clamping superior mesenteric artery of Wistar (albino) rats for 30 min, followed by reperfusion for 20 min. Immediately after reperfusion, blood samples were taken and examined for red cell copper-zinc superoxide dismutase (Cu-Zn-SOD), catalase (CAT), and glutathione peroxidase (GPx) activities spectrophotometrically and plasma zinc, copper, and magnesium concentrations by atomic absorption spectrophotometer. In the ischemia-reperfusion group, red cell Cu-Zn-SOD activity and plasma zinc and copper concentrations were increased significantly (p < 0.001) when compared to the control group; however, the increases in GPx activity and plasma magnesium concentration were not significant (p > 0.05). We also found a significant (p < 0.01) decrease in catalase activity. Free radicals released as a consequence of ischemia-reperfusion caused significant alterations in antioxidant enzymes and in the concentrations of trace elements.
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PMID:Antioxidant enzyme activities and trace element concentrations in ischemia-reperfusion. 1099 27

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