Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.15.1.1 (superoxide dismutase)
58,858 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of oxygen free radicals in ischemia and reperfusion injury of skeletal muscle has not been well defined, partly because of the relative resistance of this tissue to normothermic ischemia. Under normal conditions small quantities of oxygen free radicals are produced but they are quenched by intracellular free radical scavenging enzymes (superoxide dismutase, catalase and glutathione peroxidase) or alpha-tocopherol. The increase in malondialdehyde suggests increased lipid peroxidation initiated by free radical reactions. Lipid peroxidation is potentially a very damaging process to the organized structure and function of membranes. The results of recent studies indicate that: a) oxygen free-radicals mediates, at least in part, the increased microvascular permeability produced by reoxygenation, b) free radical scavengers can reduce skeletal muscle necrosis occurring after prolonged ischemia. Additional evidence support the hypothesis of the interrelationship between ischemic tissue and inflammatory cells. So capillary plugging by granulocytes and oxygen free radical formation may contribute to the ischemic injury.
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PMID:[Free radicals, lipid peroxidation and muscular ischemia]. 149 80

The efficacy of pharmacologic agents for prevention and control of oxygen-derived free radical damage in ischemia-reperfusion injury of the spinal cord was assessed in a swine model of thoracic and thoracoabdominal aortic crossclamping. Animals were exposed to 30 minutes of ischemia that induced lethal, irreversible injury and paraplegia. The experimental groups were as follows: group A (n = 7), control group, receiving no pharmacologic intervention; group B (n = 7), deferoxamine 50 mg/kg/day administered intravenously over 3 to 4 hours before ischemia; group C (n = 7), allopurinol pretreatment 50 mg/kg/day for 3 days; and group D (n = 7), superoxide dismutase 60,000 units administered with 50,000 units before removal of the aortic crossclamp and 10,000 units over 10 minutes of reperfusion. Proximal hypertension was controlled with sodium nitroprusside and volume depletion. The methods of assessment were neurologic by a modified Tarlov criteria and blood flow by radiolabeled microspheres. Results of blood flow assessment confirmed a true ischemic episode of 30 minutes for all animals in all groups. The blood flow fell significantly during ischemia (p less than 0.01) and a hyperemic response was evident in the early reperfusion period. All animals in control group A were paraplegic. The group B (deferoxamine) results were superior; 85% had grade III function on a modified Tarlov scale, with animals in the group standing and even walking with difficulty. Only one animal in this group had good movements of hind limbs but was unable to stand or walk. Neurologic recovery was limited in the allopurinol group (group C), with 85% showing slight neurologic recovery with limited movement of the hind limbs. The animals in the superoxide dismutase group (group D) all had good recovery, with strong motor response of hind limbs, but were not able to stand. In summary, the results of this experimental protocol confirmed the possible role of oxygen-derived free radicals in the pathophysiology of spinal cord injury, induced by aortic crossclamping. Moreover, it proved that ischemia-reperfusion injury could be altered by pharmacologic interventions.
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PMID:Pharmacologic interventions for prevention of spinal cord injury caused by aortic crossclamping. 149 87

To test the hypothesis that 5'-nucleotidase activity during ischemia is attenuated by oxygen-derived free radicals, we measured ischemia-induced reactive hyperemic flow, adenosine release, and 5'-nucleotidase activity in dogs (n = 62). A 1-minute occlusion of the coronary artery caused reactive hyperemic flow (307 +/- 5 versus 92 +/- 1 ml.100 g-1.min-1 at baseline) with increased release of adenosine (14.4 +/- 1.4 versus 0.4 +/- 0.1 nmol.100 g-1.min-1 at baseline). Superoxide dismutase augmented (p less than 0.001) both peak coronary blood flow (333 +/- 6 ml.100 g-1.min-1) and repayment (436 +/- 12 versus 320 +/- 7 ml/100 g in the untreated group). Adenosine release during reperfusion was augmented (22.7 +/- 1.9 nmol.100 g-1.min-1, p less than 0.001), and 8-phenyltheophylline completely abolished the enhanced reactive hyperemia. Enzymatic assay of 5'-nucleotidase activity revealed that the administration of superoxide dismutase increases ecto-5'-nucleotidase activity in ischemic myocardium. When an inhibitor of ecto-5'-nucleotidase, alpha, beta-methyleneadenosine 5'-diphosphate, was administered, the effects of superoxide dismutase were completely abolished. Thus, we conclude that 1) the augmentation of reactive hyperemic flow caused by superoxide dismutase is attributed to the enhanced release of adenosine and 2) the enhanced release of adenosine over the untreated controls is attributed to the protection of ecto-5'-nucleotidase activity during ischemia.
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PMID:Superoxide dismutase enhances ischemia-induced reactive hyperemic flow and adenosine release in dogs. A role of 5'-nucleotidase activity. 149 5

The mechanisms of gastric mucosal injury following a period of ischemia remain unclear. The aim of this study was to determine the relative contributions of ischemia, reperfusion, and reactive oxygen metabolites to mucosal injury induced by temporary occlusion of the celiac artery. Rats were subjected to 30 min of gastric ischemia in the presence of 100 mM HCl. Reperfusion periods ranged from 1 min to 24 hr. Drug treatments included allopurinol (100 mg/kg) or a combination of superoxide dismutase (15,000 units/kg), catalase (90,000 units/kg), and desferrioxamine (50 mg/kg). Mucosal injury was assessed by quantitative histology and the extent of macroscopic hemorrhage. Approximately one third of the total injury to the volume of the mucosa (11.8 +/- 9.1%) was due to ischemia alone. Another third was blocked by allopurinol or superoxide dismutase, catalase, and desferrioxamine (22.1 +/- 6.9%, P less than 0.001; and 25.9 +/- 4.6%, P less than 0.01), respectively, compared with control (32.5 +/- 5.1%). In contrast, extensive surface mucosal injury (62.2 +/- 27.6%) occurred primarily during ischemia and was not affected by antioxidants. Macroscopic hemorrhage was halved by treatment with allopurinol (17.5 +/- 12.6%, P less than 0.01) or superoxide dismutase, catalase, and desferrioxamine (15.9 +/- 14.5%, P less than 0.01). We conclude that temporary celiac occlusion results in gastric mucosal damage that consists of both ischemic and reperfusion components. The majority of surface mucosal injury occurred during ischemia, whereas injury to the volume of the mucosa and the vasculature occurred equally during reperfusion and was associated with reactive oxygen metabolites.
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PMID:Sequence of gastric mucosal injury following ischemia and reperfusion. Role of reactive oxygen metabolites. 150 85

The efficacy of human extracellular-superoxide dismutase type C (EC-SOD C) to limit infarct size after ischemia and reperfusion was explored and compared to that of EC-SOD C combined with catalase (CAT) and to that of CAT alone. EC-SOD C binds to heparan sulphate proteoglycan on the cell surfaces. Thirty-two pigs were subjected to 45 min of myocardial ischemia followed by 4 h of reperfusion. Control pigs (group A; n = 8) received 300 mL of saline into the great cardiac vein during a 30-min period started 5 min prior to reperfusion; pigs in group B (EC-SOD C; n = 8) got 16.6 mg of EC-SOD C; pigs in group C (EC-SOD C + CAT; n = 8) got 16.6 mg of EC-SOD C together with 150 mg of CAT. Pigs in group D (CAT; n = 8) received 150 mg of CAT. In groups B, C, and D, the drug was dissolved in saline and infused into the great cardiac. Infarct size expressed as percent of area at risk was smaller in groups B (14.5 +/- 16.7%) and C (40.8 +/- 13.3%) than in groups A (78.8 +/- 8.6%) and D (67.2 +/- 18.6%; p less than .05). Creatine kinase (CK) activity in ischemic myocardium was higher in groups B (1740 +/- 548 U/g) and C (1729 +/- 358 U/g) than in groups A (1184 +/- 237 U/g) and D (1251 +/- 434 U/g; p less than .05). There was an inverse relation (r = -.83) between infarct size and CK content. The EC-SOD C infusions resulted in only minimal increases in plasma SOD activities. In conclusion, the presence of SOD on the cell surfaces is of importance in the prevention of reperfusion injury rather than circulating SOD.
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PMID:Effects of recombinant human extracellular-superoxide dismutase type C on myocardial infarct size in pigs. 150 79

Oxygen free radicals are generated during reperfusion of ischemic organs. Studies employing several species of laboratory animal (rat, dog, pig, rabbit, mouse) have documented protective effects of a variety of free-radical scavengers and antioxidants when administered before or immediately preceding reperfusion of ischemic kidneys. These protective agents include superoxide dismutase, dimethylthiorea, dimethyl sulfoxide, alpha-tocopherol, glutathione, the iron chelator deferoxamine, probucol, allopurinol and oxypurinol, and the spin-trapping agent PBN. Furthermore, deficiency of antioxidants (selenium, alpha-tocopherol, or catalase) exacerbates postischemic renal injury. These findings have been applied to renal transplantation in an attempt to decrease the incidence of posttransplantation acute renal failure. This is important because acute renal failure results in morbidity, increases hospital stay and the cost of transplantation, and complicates the use of cyclosporine. In porcine and in canine kidney transplantation, superoxide dismutase and allopurinol have provided renal protection. Transplantation is complicated because there may be prolonged hypoperfusion before harvesting plus a brief period of total ischemia during harvesting, followed by a prolonged period of cold ischemia and/or reperfusion, then followed by another brief period of ischemia and reperfusion during transplantation. Injury may occur at each of these phases by different mechanisms.
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PMID:Free radical-mediated postischemic injury in renal transplantation. 150 58

This study was designed to test the hypothesis that the oxygen free radical scavengers superoxide dismutase (SOD) and catalase may reduce myocardial "stunning" after exercise-induced ischemia. To test this hypothesis, 8 mongrel dogs performed treadmill exercise for 10 min in the presence of a flow-limiting coronary artery stenosis. Regional left ventricular function was measured with ultrasonic microcrystals implanted to measure regional wall thickening. Regional myocardial perfusion was measured with radioactive microspheres. The combination of SOD (5 mg/kg iv) and catalase (5 mg/kg iv) did not affect heart rate, blood pressure, coronary artery flow, or regional myocardial blood flow at rest, during exercise, or in the postexercise period. SOD and catalase had no effect on regional wall thickening at rest before exercise. During exercise in the absence of a coronary artery stenosis, thickening was slightly lower during SOD and catalase infusion (27 +/- 11.0 vs. 30.8 +/- 11.5%, SOD vs. control P = 0.05). During exercise in the presence of a coronary artery stenosis, there was no difference in thickening. Infusion of SOD and catalase affected neither the transient rebound function occurring early after exercise nor the prolonged period of stunning. These results indicate that the myocardial stunning that follows exercise-induced ischemia is unlikely to be mediated by oxygen free radicals.
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PMID:Effect of superoxide dismutase and catalase on regional dysfunction after exercise-induced ischemia. 151 Jan 36

The efficacy of recombinant human extracellular-superoxide dismutase type C (EC-SOD C) on myocardial reperfusion injury was explored in hypothermically arrested rat hearts, as was its site of action. Forty isolated working rat hearts were subjected to 30 min of global ischemia followed by 30 min of reperfusion. The hearts were arrested by the administration of 10 mL of cold perfusate at the onset of ischemia. At the same time, they were randomly assigned to one of five groups; A: cold perfusate only; B: cold perfusate + EC-SOD C 10.4 mg/L (30,000 U/L); C: cold perfusate+bovine CuZn-SOD 7.5 mg/L (30,000 U/L); D: cold perfusate + EC-SOD C 10.4 mg/L + heparin 50,000U/L; E: cold perfusate + heparin 50,000 U/L. Heparin was given to prevent binding of EC-SOD C to endothelial cell surfaces. Left ventricular function was studied before ischemia and at the end of reperfusion. Percent recovery of maximal left ventricular dP/dt after reperfusion was more pronounced in group B (109 +/- 24%; p less than .05) than in groups A (42 +/- 40%), C (47 +/- 36%), D (44 +/- 33%) and E (58 +/- 25%). Likewise, percent recovery of the double product (heart rate x systolic left ventricular pressure) was better in group B (104 +/- 18%; p less than .05) than in the other groups (A: 47 +/- 37%, C: 49 +/- 36%, D: 50 +/- 35%, E: 69 +/- 31%). Compared to the preischemic level, creatine kinase increased significantly in the coronary effluent after reperfusion in groups A, C, D, and E, but not in group B. The results suggest that EC-SOD C, which attaches to the endothelial cell surfaces, might be particularly effective as protection against myocardial reperfusion injury when given together with cardioplegic solution.
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PMID:Effects of recombinant human extracellular-superoxide dismutase type C on myocardial reperfusion injury in isolated cold-arrested rat hearts. 151 40

During the procedure of coronary artery bypass graft surgery (CABG), the release of free oxygen radicals as a result of ischemia and reperfusion which plants the seeds of post-operative low cardiac output and arrhythmias has grave consequence on the reestablishment of cardiac function. A variety of chemical agents such as mannitol, allopurinol, catalase (Q-10) and superoxide dismutase (SOD) has proved to be considerably effective to improve the myocardial necrosis following ischemia and reperfusion. In this study we chose mannitol (0.2 gm/kg) as the free oxygen radicals scavenger and utilized mass spectrophotometric method to detect the variation of concentration of [H2O2], a by-product of free oxygen radical, in an attempt to evaluate the efficacy of mannitol in this regard in patients undergoing CABG. Patients were divided into experimental group (n = 19) and control group (n = 20). In the experimental group the concentration of [H2O2] changed from 61 +/- 24 microM/L pre-operatively to 77 +/- 18 microM/L post-operatively as against 75 +/- 31 microM/L and 99 +/- 31 microM/L respectively in the control group. In comparison, only the change in experimental group was statistically significant (p less than 0.05). We confirmed that mannitol functions considerably as a free oxygen radical scavenger since it reduces the production of [H2O2] in patients undergoing CABG.
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PMID:[Mannitol reduces plasma hydrogen peroxide free radical in patients undergoing coronary artery bypass graft surgery]. 152 1

In this study rat epigastric island flaps were used as a model to investigate selected tissue biochemical changes occurring during secondary ischemia. It was hypothesized that free radical damage, depletion of free radical scavengers, depletion of ATP, and increased edema might explain differences in flap survival between partial (venous obstruction) and total (arteriovenous obstruction) ischemia and decreased flap survival with increasing ischemia time. Flaps were given 2 hr or primary ischemia, 8 hr of normal perfusion, then secondary ischemia of 0, 2, 4, 8, or 12 hr with either arteriovenous obstruction or venous obstruction. Biochemical analysis of the skin was performed after 0, 24, or 96 hr reperfusion. Only minor differences were found between arteriovenous and venous ischemia for any of five biochemical parameters, despite a previous finding that venous ischemic flaps are more susceptible to necrosis. Levels of xanthine oxidase and malonyldialdehyde (both indices of free radical generation) increased with ischemia time. Levels of superoxide dismutase (a free radical scavenger) correspondingly decreased. Tissue levels of ATP decreased after ischemia and recovered to normal for shorter but not for longer ischemia times after 96 hr of reperfusion in parallel with flap survival. Edema increased immediately after the ischemic insult but decreased once the tissue became necrotic. These results imply roles for free radicals, ATP, and edema in secondary ischemia, but do not distinguish between arteriovenous and venous secondary ischemia.
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PMID:The biochemical basis of secondary ischemia. 153 98


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