Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.17.3.2 (xanthine oxidase)
 8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was designed to clarify the mechanism of ischemia-reperfusion-induced rat liver injury and to evaluate the effect of long-acting superoxide dismutase (SOD-POE). Liver mitochondrial functional indices, i.e., the respiratory control index (RCI) and the rate of oxygen consumption in State III respiration (St. III O2), were decreased significantly to 1.33 +/- 0.06, mean +/- SD, and 54.4 +/- 3.7 natom/mg protein/min, respectively, after 120 min of ischemia, compared to respective preischemic values (3.94 +/- 0.21 and 80.2 +/- 3.9). These indices did not recover fully following 60 min of reperfusion (RCI, 3.25 +/- 0.17; St. III O2, 69.9 +/- 6.4). Tissue levels of adenosine triphosphate (ATP) were decreased to 2% of preischemic levels after 120 min of ischemia and remained at 39% of preischemic levels following 60 min of reperfusion. Increases in hypoxanthine and xanthine were observed after ischemia. SOD-POE improved the recovery of mitochondrial function (RCI, 3.70 +/- 0.20; St. III O2, 83.3 +/- 7.6) and also accelerated the recovery of ATP (53% of preischemic level). SOD-POE did not affect the decrease in ATP levels or the increase in purine nucleotide levels during ischemia. SOD-POE did not influence changes in tissue blood flow levels throughout the experiments. The leakage of adenine nucleotides immediately after reperfusion was observed (4.2 +/- 2.0 mumole/liter serum), and SOD-POE mitigated this leakage (1.3 +/- 0.5). Purine nucleotides are oxidizable substrates of xanthine oxidase, and an increase in superoxide radical generation by this enzyme might be expected in the ischemia-reperfusion process.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanism and prevention of ischemia-reperfusion-induced liver injury in rats. 188 Nov 38

This study was undertaken to determine whether hepatic ischemia and the subsequent reflow of blood have any effect on the conversion of xanthine dehydrogenase to xanthine oxidase (XO). Ischemia of the liver for 90 or 120 minutes did not permit survival of the animals. XO represented 15% of the total xanthine dehydrogenase plus XO activity in the control liver. XO activity remained unchanged even after 90 minutes of hepatic ischemia, although a marked increase in lipid peroxide in the liver tissue was observed during the reperfusion. When hepatic ischemia was prolonged for 6 hours (animals were dead), XO activity rose to 35% of the total activity. Incubation of the liver at 37 degrees C resulted in a definite change in XO activity dependent on the length of incubation period. Although no significant changes occurred in XO activity during the first 2 hours of incubation, a marked XO conversion was observed between 2 and 4 hours, and a maximal conversion was achieved after 6 hours of incubation. These results suggest that XO newly generated during ischemia has a very limited role in oxygen free radical production after resuming perfusion.
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PMID:Role of conversion of xanthine dehydrogenase to oxidase in ischemic rat liver cell injury. 188 78

The effect of repeated administration of allopurinol (50 mg.kg-1 48, 24, and 4 hours before analysis) on the activity of enzymes of degradation and resynthesis of adenine nucleotides was studied. The activity of xanthine dehydrogenase and xanthine oxidase was inhibited in the heart, liver and kidney and the activity of membrane-bound 5'-nucleotidase was particularly elevated in the heart and brain, suggesting that membrane transport processes may be affected. The increase in the activity of hypoxanthine guanine phosphoribosyl transferase in the liver is indicative of a potential mechanism of positive action of allopurinol upon restoring the purine nucleotide store. The authors present their hypothesis on the mechanism of allopurinol action upon the metabolism of adenine nucleotides. The suggested mechanisms might become operative in protecting tissues against ischemia and reperfusion induced damage.
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PMID:[Mechanisms of the effect of allopurinol on the metabolism of adenine nucleotides]. 191 98

An in vitro canine tibia model was used to assess the effects of 48 h of hypothermic (4 degrees C) ischemia on bone vascular resistance and on responsiveness of intraosseous blood vessels to circulating norepinephrine. Three groups of bones were studied: Group I (n = 11), 48 h hypothermic ischemia; Group II (n = 11), 48 h hypothermic ischemia with pretreatment with allopurinol and oxypurinol; and Group III (n = 10), no ischemia. Resting vascular resistance in both ischemic groups (79 and 74 mmHg/ml/min) was significantly higher (p less than 0.0001) than in the nonischemic group (22 mmHg/ml/min). Effects of norepinephrine on vascular resistance were significantly greater in both ischemic groups (p less than 0.004). In all three groups, acetylcholine infusion attenuated the increases in perfusion pressure caused by norepinephrine. This demonstrates secretion of endothelial-mediated relaxing factors (EDRF) and prostaglandin for up to 48 h of hypothermic ischemia. As no significant differences were detected between the two ischemic groups, this study failed to demonstrate any protective effect of xanthine oxidase inhibitors.
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PMID:The effects of ischemia on long bone vascular resistance. 191 52

Ischemia-reperfusion injury has been implicated as playing a major role in the development of necrotizing enterocolitis, a major cause of morbidity and mortality in the newborn. A tungsten-supplemented molybdenum-free diet can reduce xanthine oxidase (XO) enzyme activity in the intestine, which in turn reduces the generation of oxygen radicals after an ischemia-reperfusion insult. This study evaluated the ability of this diet to be effective by indirect means, ie, transplacental and breast-feeding routes. XO activity of the intestine was measured in three groups of CD-1 white rats: I, weanlings fed the tungsten diet or standard chow for 1 week; II, 1-day-old rat pups whose mothers were maintained on the tungsten or standard chow for 7 to 10 days prior to term; and III, rat pups at 1 and 3 weeks after birth whose lactating mothers were maintained on the tungsten or standard chow. Some animals from group III also underwent either a 30- or 60-minute episode of occlusion of the superior mesenteric artery (SMA) to evaluate the protective effects of the diet. XO activity was significantly reduced in all groups receiving the tungsten diet (P less than .0001). Blinded histopathologic studies of the entire small bowel showed significantly less villar necrosis (P less than .05) and fibrosis (P less than .0001) in the tungsten-treated group than in the controls. In the 60-minute occlusion study all tungsten-group animals survived, whereas 7 of 12 in the control group died of intestinal infarction within 24 hours (P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A tungsten-supplemented diet delivered by transplacental and breast-feeding routes lowers intestinal xanthine oxidase activity and affords cytoprotection in ischemia-reperfusion injury to the small intestine. 191 86

Alteration in oxidant-antioxidant balance is a key feature of many common vascular diseases. Using an isolated perfused heart model, we found that (a) xanthine oxidase-derived oxygen radicals contributed to ischemia-reperfusion injury; (b) addition of antioxidants within or outside erythrocytes decreased injury following ischemia-reperfusion; (c) endotoxin pretreatment increased myocardial catalase activity and decreased injury following ischemia-reperfusion; (d) interleukin pretreatment increased myocardial glucose-6-phosphate activity and decreased ischemia-reperfusion injury, and (e) neutrophils mediated tolerance to a subsequent oxidative stress by causing a small oxidant stress that in turn increased antioxidant protection mechanisms.
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PMID:Oxidant-antioxidant balance: some observations from studies of ischemia-reperfusion in isolated perfused rat hearts. 192 11

Oxygen free radicals (OFR) are thought to mediate ischemia-reperfusion injury to endothelium of heart, lung, brain, liver, and kidney and contribute to development of atherosclerosis, pulmonary O2 toxicity, and adult respiratory distress syndrome. Increased cytosolic free Ca2+ (Cai2+) has been proposed as a mechanism of injury from oxidative stress, yet the pathways by which an increase in Cai2+ may cause OFR-mediated endothelial cell injury remain unknown. Using multiparameter digitized video microscopy and the fluorescent probes, fura-2 acetoxymethyl ester and propidium iodide, we measured Cai2+ and cell viability in human umbilical endothelial cells during oxidative stress with xanthine (50 microM) plus xanthine oxidase (40 mU/ml). Oxidative stress caused a sustained increase in Cai2+ from a resting level of 90-100 nM to near 500 nM, which was preceded by formation of plasma membrane blebs. The increase in Cai2+ was prevented by removal of extracellular Ca2+ (Cao2+). Prevention of the increase in Cai2+ was associated with prolonged cell viability. Readdition of Cao2+ resulted in an immediate large increase in Cai2+ and rapid onset of cell death. The protease inhibitors, leupeptin and pepstatin, delayed the increase in Cai2+ and prolonged cell viability. The results are consistent with the hypothesis that endothelial cell injury due to oxidative stress may be the result of Cai2+ influx and resultant activation of Ca(2+)-dependent proteases.
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PMID:Cytosolic free Ca2+ and proteolysis in lethal oxidative injury in endothelial cells. 195 73

Elevation of a vascular island flap 24 hours before an ischemic insult (prior elevation) has been shown to significantly increase flap survival, and to decrease blood thromboxane levels, compared with acutely ischemic flaps. The current study considered whether prior elevation causes other biochemical alterations that could be beneficial for flap survival. Tissue levels of adenosine triphosphate (a major tissue energy store), superoxide dismutase (a major defense against free radicals), xanthine oxidase (an enzymatic source of free radicals), and edema were measured. Rat epigastric flaps, with or without prior elevation, had 10 or 12 hours of acute ischemia. Biopsies were taken at 0, 12, or 24 hours after reperfusion. Skin from flaps with no ischemia (control flaps) or control skin was harvested at the same times. Acutely ischemic flaps had significantly lower levels of adenosine triphosphate and less edema than those in prior elevated ischemic flaps after 12 hours of ischemia (both, p less than 0.05). Superoxide dismutase and xanthine oxidase did not vary significantly. It is not clear whether the increased adenosine triphosphate level in prior elevated flaps is the cause or the result of increased tissue viability. Prior elevation did not alter free radical mechanisms. Furthermore, prior elevation was beneficial for flap survival despite increased edema.
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PMID:A biochemical study of acute ischemia in rodent skin free flaps with and without prior elevation. 195 13

Although cardiac dysfunction due to ischemia-reperfusion injury is considered to involve oxygen free radicals, the exact manner by which this oxidative stress affects the myocardium is not clear. As the occurrence of intracellular Ca2+ overload has been shown to play a critical role in the genesis of cellular damage due to ischemia-reperfusion, this study was undertaken to examine whether oxygen free radicals are involved in altering the sarcolemmal Ca2(+)-transport activities due to reperfusion injury. When isolated rat hearts were made globally ischemic for 30 min and then reperfused for 5 min, the Ca2(+)-pump and Na(+)-Ca2+ exchange activities were depressed in the purified sarcolemmal fraction; these alterations were prevented when a free radical scavenger enzymes (superoxide dismutase plus catalase) were added to the reperfusion medium. Both the Ca2(+)-pump and Na(+)-Ca2+ exchange activities in control heart sarcolemmal preparations were depressed by activated oxygen-generating systems containing xanthine plus xanthine oxidase and H2O2; these changes were prevented by the inclusion of superoxide dismutase and catalase in the incubation medium. These results support the view that oxidative stress during ischemia-reperfusion may contribute towards the occurrence of intracellular Ca2+ overload and subsequent cell damage by depressing the sarcolemmal mechanisms governing the efflux of Ca2+ from the cardiac cell.
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PMID:Alterations in cardiac membrane Ca2+ transport during oxidative stress. 196 45

Excessive stimulation of excitatory amino acid (EAA) receptors and abnormal production of oxygen-derived free radicals have repeatedly been implicated in the series of events linking brain hypoxia or ischemia to neuronal death. We report here that in rat hippocampal slices the KCl-stimulated output of labeled D-3H aspartate or of endogenous aspartate and glutamate significantly increased under in vitro simulated hypoxic, hypoglycemic, or ischemic conditions. In particular, when the slices were incubated for 10 min at 32 degrees C under "ischemic" conditions (namely, lack of oxygen and glucose), endogenous aspartate and glutamate in the supernatant increased by 10 and 20 times, respectively. Since radical scavengers (D-mannitol), drugs reducing free radical formation (indomethacin, corticosteroid), or enzymes able to metabolize them (catalase and superoxide dismutase) significantly reduced this output, it was supposed that free radicals caused EAA release. A direct demonstration of this concept was obtained by showing a significant release of EAA after incubation of hippocampal slices with enzymes and substrates known to cause the formation of free radicals, such as xanthine plus xanthine oxidase or arachidonic acid plus prostaglandin synthase. Neither ischemia nor the enzymatic reactions leading to free radical production increased the activity of the cytoplasmic enzyme lactate dehydrogenase in the incubation medium, thus ruling out a nonspecific cellular lysis. It appears therefore that during ischemic states, brain production of reactive molecules (free radicals) causes an increased output of EAA. This may trigger a series of events which could help to explain the delayed loss of neurons after a transient ischemic period.
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PMID:Excitatory amino acid release and free radical formation may cooperate in the genesis of ischemia-induced neuronal damage. 196 65


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