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)

It has been suggested that oxidative processes are involved in a variety of pathological conditions, notably ischemia-reperfusion injury. Moreover, anesthetics appear to exert differential effects on the severity of such injury, these being unlikely wholly attributable to their differential effects on cardiovascular or microcirculatory status. It is possible that these variable effects of anesthetics on this type of injury may be due, at least in part, to changes in the production of free radicals and/or in their detoxification by endogenous antioxidant enzymes. We have attempted to explore the latter possibility by measuring activities of catalase, superoxide dismutase (SOD), glutathione peroxidase (GPX) and glutathione reductase in normal heart tissue and red cells obtained from rats anesthetized using a variety of agents (CO2, halothane, pentobarbital or ether). For comparison, analyses were also performed on tissues from unanesthetized animals rendered unconscious by stunning prior to sacrifice. Results indicated that myocardial SOD activity was significantly greater in halothane-anesthetized as compared with CO2-anesthetized animals. Red cell SOD activities did not show such differences. However, red cell GPX activity was found to be greater in halothane-anesthetized than in pentobarbital-anesthetized rats. In general, however, antioxidant enzyme activities measured ex vivo were minimally affected by the use of anesthetics prior to euthanasia. Our findings, therefore, do not support the proposal that the influence of anesthetics on the course of ischemia-reperfusion injury involves effects at the level of enzymatic antioxidant components.
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PMID:Effects of various anesthetic regimens on tissue antioxidant enzyme activities. 816 73

Free radical-initiated lipid peroxidation (LP) following intestinal ischemia/reperfusion (I/R) may disrupt mucosal integrity. It is unknown if inhibition of LP prevents this injury. We analyzed rat ileum, subjected to I/R, for evidence of LP inhibition and structural damage following treatment with the 21-aminosteroid, U74389F, a potent LP inhibitor. Four groups of Lewis rats were studied after superior mesenteric artery occlusion with ligation of collateral arcades: (i) no ischemia, (ii) 10 min ischemia, (iii) 10 min ischemia + 1 hr reperfusion, (iv) 10 min ischemia + 1 hr reperfusion + U74389F (6 mg/kg i.v. prior to clamp removal and reperfusion). Ileal mucosa was analyzed for: 9i0 superoxide dismutase (SOD; U/mg protein), a key antioxidant enzyme, (ii) myeloperoxidase (MPO; U/mg protein), an index of PMN stimulation, (iii) malondialdehyde (MDA; pmole/mg), an end product of LP, and (iv) routine histology. MDA rose from 2.09 +/- 0.44 (mean +/- SE) in Group 1 to 15.10 +/- 2.22 in Group 3 following I/R (P < 0.01). In Group 2 and Group 4, MDA remained unchanged at 3.25 +/- 1.38 and 1.73 +/- 0.15, respectively. MPO, likewise, rose during I/R from 0.59 +/- 0.17 in Group 1 to 1.10 +/- 0.13 in Group 3 (P = 0.08) and 1.49 +/- 0.24 in Group 4 (P < 0.05). SOD did not vary significantly in the four groups studied. Despite PMN stimulation indicated by increased MPO with reperfusion, no PMN infiltration was seen histologically. U74389F normalized MDA, indicating effective inhibition of LP; however, similar epithelial sloughing and edema and hemorrhage in the lamina propria were seen in treated and untreated rats. These data implicate MDA-independent or possibly LP-independent pathways in intestinal morphologic damage occurring with I/R.
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PMID:Inhibition of intestinal lipid peroxidation does not minimize morphologic damage. 823 Nov 75

The effect of ischemia-reperfusion on activity, protein and m-RNA levels of catalase, copper-zinc and manganese containing superoxide dismutases and glutathione peroxidase, the enzymes that are involved in free radical detoxification was studied in rat kidney. Ischemia alone did not alter either the activities or protein levels of superoxide dismutase and glutathione peroxidase. However, catalase activity was found to be inhibited to 82% of control. The inhibition of catalase was due to the inactivation of the enzyme as there was no significant change in enzyme protein level. Reperfusion following ischemia, however, led to a significant decrease in both the activities as well as the protein levels of all the antioxidant enzymes. The observed overall decrease in total superoxide dismutase activity was the net effect of a decrease in copper-zinc superoxide dismutase while manganese superoxide dismutase activity was found to be increased following reperfusion. This observed increase manganese superoxide dismutase activity was the result of its increased protein level. The mRNA levels for catalase, superoxide dismutases, and glutathione peroxidase were observed to be increased (100-145% of controls) following ischemia; reperfusion of ischemic kidneys, however, resulted in a significant decrease in the levels of mRNAs coding for all the enzymes except manganese superoxide dismutase which remained high. These results suggest that in tissue, the down regulation of the antioxidant enzyme system could be responsible for the pathophysiology of ischemia-reperfusion injury.
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PMID:Expression of antioxidant enzymes in rat kidney during ischemia-reperfusion injury. 828 74

Superoxide dismutase is well known to act as an effective antioxidant enzyme against cellular damage caused by oxidative stresses including ischemia/reperfusion-induced cerebral injury. However, it is still controversial whether or not the activity of endogenous superoxide dismutase changes during cerebral ischemia and reperfusion. In order to elucidate this phenomenon, we assayed the superoxide dismutase activity in the cerebral tissues of gerbils using the chemiluminescence method with a Cypridina luciferin analog. This method was demonstrated to be a sensitive and specific assay for the enzymatic activity of superoxide dismutase in cerebral tissues, which was not subject to interference from proteins or ascorbate. After 3 h of focal and global ischemia, there were no changes in the cerebral tissue superoxide dismutase activities. After 24 h of reperfusion following 1 h of ischemia, the superoxide dismutase activity decreased only approx 20%, whereas the adenylate kinase activities, measured in the same cerebral tissues as those used for superoxide dismutase assay, started to decline 1 h after reperfusion commenced and were approx 50% of the control levels after 24 h. These results show that almost all the activity of endogenous superoxide dismutase is maintained and does not decrease significantly as a result of ischemia/reperfusion-induced cerebral injury.
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PMID:The superoxide dismutase activities of cerebral tissues, assayed by the chemiluminescence method, in the gerbil focal ischemia/reperfusion and global ischemia models. 836 36

This study examined whether brief repeated myocardial ischemia altered free radical generating and scavenging activity in a dog model. In dogs preconditioned with four 5-min left anterior descending coronary artery (LAD) occlusions and reperfusions, we examined transcardiac changes in both the function of neutrophils, cells which are major free radical generators, and in myocardial antioxidant enzyme activity, as an indication of free radical scavenging. Neutrophil function was assessed by determining luminol-enhanced whole blood chemiluminescence (CL) induced by zymosan. Blood was taken simultaneously from the carotid artery and the cardiac vein running along the occluded LAD. Preconditioning with sublethal ischemia significantly reduced whole blood CL in the cardiac vein compared with the carotid artery after the first and fourth 5-min reperfusions, while there was no difference in neutrophil count between these sampling sites. Immediately after brief repeated ischemia and reperfusion, manganese-superoxide dismutase (SOD) activity was significantly enhanced, and glutathione reductase activity was markedly reduced in the ischemic, compared with the non-ischemic, myocardium. There were no differences in the myocardial activities of copper, zinc-SOD, glutathione peroxidase, and glutathione S-transferase between the ischemic and non-ischemic regions. Also, no difference was observed between the reduced myocardial glutathione levels in these regions, although the oxidized glutathione level was significantly higher in the ischemic regions of the subepicardial and subendocardial areas. We demonstrated that brief repeated ischemia affects free radical generating and scavenging systems in the ischemic myocardium.
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PMID:Brief myocardial ischemia affects free radical generating and scavenging systems in dogs. 840 20

To assess the role of Cu-Zn superoxide dismutase (CuZnSOD) in regulating cellular antioxidant defenses, we studied the induction of CuZnSOD mRNA by an in situ hybridization technique and of CuZnSOD protein by an immunocytochemical method in the gerbil hippocampus following 5 min of transient global ischemia. For hybridization, we synthesized 48-mer oligonucleotide (base 465-512) complementary to rat CuZnSOD mRNA. Northern blot analysis showed hybridization to a single band of molecular weight 0.65 kb. After 5 min of ischemia, the signal became stronger at 3 and 24 h and returned to the control level 3 days later. In situ hybridization histochemistry revealed an increase in labeling throughout the hippocampus, especially in the granular layer 3 h following ischemia. The increase was prolonged only in the CA1 pyramidal layer after 24 h and was eliminated within 3 days or later. Conversely, analysis by Western blotting revealed that the insult produced few effects on the induction of CuZnSOD protein. Immunocytochemistry for CuZnSOD revealed a reduced immunostaining in the CA1 pyramidal layer at 24 h of recirculation when the persistent expression of CuZnSOD mRNA was shown in the same area. Our findings suggest that the expression of endogenous CuZnSOD is temporarily stimulated by an ischemic insult without increasing the protein level. The prolonged increase in mRNA and the decrease in the protein of CuZnSOD in the CA1 neurons seem to imply an important role of the endogenous antioxidant enzyme that protects against the detrimental effects of superoxide radicals on delayed neuronal death.
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PMID:Induction of copper-zinc superoxide dismutase in gerbil hippocampus after ischemia. 841 2

We studied the recovery of retinal pigment epithelium and retinal function after 80 minutes of pressure-induced ischemia in rabbits. Just before restoring circulation, we gave intravenous mannitol (an osmotic agent and free-radical scavenger), dextromethorphan (an N-methyl-D-aspartate receptor antagonist), or catalase (an antioxidant enzyme). Mannitol has not previously been shown to be protective for retinal or retinal pigment epithelial ischemia. At 24 hours after reperfusion, the electroretinogram b-wave was reduced to 37% of preischemic amplitude in untreated eyes, but it recovered to 67% to 80% after treatment with all three agents. The c-wave was replaced by a negative slow PIII response in control eyes and in seven of 12 catalase-treated eyes, but it recovered by 58% to 82% in the remaining catalase-treated eyes and all the mannitol- and dextromethorphan-treated eyes. Histologic examination confirmed that retinal pigment epithelium as well as retina had been damaged by the ischemia. The effects of mannitol seem of special interest, since the drug has a dual mechanism of action and is clinically available.
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PMID:Mannitol, dextromethorphan, and catalase minimize ischemic damage to retinal pigment epithelium and retina. 844 53

Time-dependent changes in levels of the antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GSHPOD), and catalase (CAT) after cortical focal ischemia in rat indicate that: (1) primary and peri-ischemic tissues differ in both rate and the magnitude of oxyradical-induced ischemic injury, and (2) ischemic tissue remains vulnerable to oxyradical damage as long as 72 h after ischemia since the antioxidant enzyme levels remain at or below basal levels. After 72 h, the increased levels of these enzymes are sufficient to protect tissue against oxyradical damage. GM1 ganglioside (10 mg/kg, im) further increased the already elevated levels of the enzymes after ischemia, thereby indicating the GM1 treatment increases the capacity of ischemic tissue to protect against oxyradical injury.
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PMID:Temporal changes in superoxide dismutase, glutathione peroxidase, and catalase levels in primary and peri-ischemic tissue. Monosialoganglioside (GM1) treatment effects. 846 85

Over a 10-week period, female Wistar rats received a diet containing various levels of four trace elements (Zn, Cu, Mn, Se), co-factors of antioxidant enzymes (superoxide dismutase SOD, glutathione peroxidase GPx), in order to examine the influence of supplementation or deficiency of these elements (i) on tissue antioxidant enzyme defence systems, and (ii) on the susceptibility of the myocardium to ischemia-reperfusion injury. At the end of the dietary treatment, hearts were perfused at constant flow (11 ml/min) before being subjected to 15 min of total global normothermic ischemia, followed by reperfusion. The effects of the various diets (deficient, standard or supplemented) were estimated by studying functional recovery of various cardiac parameters (left ventricular developed pressure LVDP, dP/dtmax, heart rate x LVDP) as well as ultrastructural tissue characteristics. Furthermore, SOD and GPx activities were measured before ischemia and at the end of the reperfusion period. Results suggest that: (a) the activity of antioxidant enzymes increased or decreased significantly when diet was respectively supplemented with, or deficient in, trace elements, but was not further modified by an ischemia-reperfusion episode: (b) the recovery of cardiac function during reperfusion, and ventricular myocardial ultrastructure were significantly improved under the influence of trace element supplementation when compared to both standard and deficient groups. These results illustrate the protective effect of trace elements which are co-factors of antioxidant enzymes in limiting ischemia-reperfusion induced injury, and suggest a possible use in the field of anti-ischemic therapy.
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PMID:Effect of dietary antioxidant trace element supply on cardiac tolerance to ischemia-reperfusion in the rat. 857 45

Oxidative mechanisms of damage have been implicated indirectly in the damage to brain tissue caused acutely by ischemia or chronically by neurodegenerative diseases. A direct link between pathogenesis and antioxidant enzyme systems has come from studies of a genetic form of amyotrophic lateral sclerosis (ALS). ALS causes the degeneration of motor neurons in cortex, brainstem and spinal cord with consequent progressive paralysis and death. The disease occurs in both sporadic and familial forms. Some 20% of kindreds in which ALS is inherited in an autosomal dominant fashion have mutations in the gene (SOD1) encoding Cu, Zn superoxide dismutase (SOD). Several SOD1 mutations have been shown by ourselves and others to cause motor neuron disease when expressed at high levels in transgenic mice, whereas transgenic mice expressing comparable amounts of wild-type human SOD do not show clinical disease. Thus, we have argued that motor neuron disease is caused by gain-of-function mutations in the human SOD1 gene. Our current experiments investigate the link between mutation of SOD1 and oxidative pathways of damage.
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PMID:Pathogenic mechanisms in familial amyotrophic lateral sclerosis due to mutation of Cu, Zn superoxide dismutase. 873 1


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