Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.17.1.4 (xanthine dehydrogenase)
 1,236 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The superoxide radical plays major roles in the neutrophil-medicated acute inflammatory response and in postischemic tissue injury, although the sources and actions of the radical are quite different in these two pathological states. While neutrophils produce superoxide for the primary purpose of aiding in the killing of ingested microbes, a second useful function has evolved. The superoxide released from actively phagocytosing neutrophils serves to attract more neutrophils by reacting with, and activating, a latent chemotactic factor present in plasma. Superoxide dismutase, by preventing the activation of this superoxide-dependent chemotactic factor, exerts potent anti-inflammatory action. During ischemia, energy-starved tissues catabolize ATP to hypoxanthine. Calcium transients in these cells appear to activate a calmodulin regulated protease which attacks the enzyme xanthine dehydrogenase, converting it to a xanthine oxidase capable of superoxide generation. When the tissue is reperfused and reoxygenated, all the necessary components are present (xanthine oxidase, hypoxanthine, and oxygen) to produce a burst of superoxide which results in extensive tissue damage. Ischemic tissues are protected by superoxide dismutase or allupurinol, an inhibitor of xanthine oxidase.
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PMID:The pathophysiology of superoxide: roles in inflammation and ischemia. 629 73

Reactive oxygen species play an important role in pathogenesis of a variety of pathological processes, e.g., ischemia-reperfusion, acute viral infections, thermal injury, hepatic diseases, and acute lung injury. Xanthine oxidase (XO) may be a significant source of these cytotoxic oxygen species. We tested the hypothesis that hepatic ischemia-reperfusion releases xanthine dehydrogenase + XO (XDH + XO) into the circulation and that circulating XO damages isolated perfused lung. Isolated liver + lung preparation was perfused with Krebs-Henseleit buffer to minimize confounding effects of circulating neutrophils. In one group, livers were rendered globally ischemic for 2 h and then reperfused (I/R). In another group, livers were pretreated with allopurinol and perfused with buffer containing additional allopurinol (I/R + Allo). After 2 h of ischemia, an isolated lung was connected to liver, and liver + lung preparation was reperfused in series for 15 min. Liver reperfusion was terminated, and lung was recirculated with liver effluent for 45 min. Capillary filtration coefficient (ml.min-1.cmH2O-1.100 g lung dry wt-1) was 2.0 +/- 0.3 and 1.9 +/- 0.4 in control and I/R + Allo lungs, respectively, and 9.0 +/- 1.2 in I/R lungs (P < 0.001). Lung wet-to-dry weight ratio in control and I/R + Allo lungs was 8.6 +/- 0.3 and 9.1 +/- 0.5, respectively, and 14.9 +/- 1.1 in I/R lungs (P < 0.01). Control and I/R + Allo bronchoalveolar lavage protein content was < 1.0 mg/ml compared with 32.6 +/- 8.4 mg/ml in I/R group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Liver ischemia-reperfusion increases pulmonary permeability in rat: role of circulating xanthine oxidase. 761 20

Warm and cold ischemia-reperfusion injuries to canine small intestine was compared. In the warm ischemic model, the superior mesenteric artery of mongrel dogs was clamped for 2 h and then released (group A). As a cold ischemia model, canine small intestines were harvested with cold lactated Ringer solution, preserved for 24 h in cold LR solution and then autotransplanted (group B). After ischemia and during reperfusion, activities of maltase (MAL), myeloperoxides (MPO), xanthine dehydrogenase (XD) and xanthine oxidase (XO) were measured as well as hypoxanthine (HX) concentration. MAL activities were not changed during warm or cold ischemia, whereas it was remarkably decreased after revascularization in both the groups. Neutrophil infiltration after reperfusion was shown by the increase of MPO activities to 8 and 1.5 U/mg protein in groups A and B respectively from a normal value of 0.35 U/mg protein. During warm ischemia, %XO (XO/XD + XO) was increased from 18.4 to 84.9% for 2 h. In contrast, %XO was not changed for 24 h of cold ischemia. Tissue accumulation of HX was increased 2.8 times from a normal value of 1.06, 2 h after warm ischemia, but there was almost neither accumulation of HX nor the conversion of XD to XO in 24 h cold ischemia. It was observed that warm and cold ischemia caused similar injury after reperfusion in spite of the striking difference in the conversion of XD to XO and accumulation of HX. Thus, it is suggested that the XO system is not always necessary for ischemia-reperfusion injury.
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PMID:Comparison of warm and cold ischemia of the canine small intestine. 764 10

Xanthine oxidase and xanthine dehydrogenase are enzymes involved in the metabolism of purines and pyrimidines in various organisms. Their relationship to one another has been the subject of considerable debate, primarily because of their proposed roles in ischemia/reperfusion damage in tissues. Differences in the kinetics and oxidation-reduction behavior of the two forms are accounted for by the presence in the dehydrogenase of a binding site for NAD+, as well as a substantially lower reduction potential for the flavin FADH./FADH2 couple of the dehydrogenase relative to the oxidase. This review presents recent advances of our understanding of the biochemistry and molecular biology of these systems, including a model for the overall morphology of xanthine oxidizing enzymes. The evidence that the two enzymes represent alternate forms of the same gene product, in some cases reversibly interconvertible between one another, is discussed.
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PMID:Flavoprotein structure and mechanism. 4. Xanthine oxidase and xanthine dehydrogenase. 764 15

Reactive oxygen species (ROS) generated from xanthine oxidase (XO) play an important role in ischemia-induced injury. We hypothesize that XO and xanthine dehydrogenase (XDH) are released into the circulation with ischemia reperfusion to the human liver and intestine. Blood was drawn from a patient, before and at intervals after an aortic cross-clamp procedure. Plasma was incubated in the presence of xanthine, with NAD+ (for XD +XO) and without NAD+ (for XO). The amount of urate formed was quantified using a high-performance liquid chromatograph (HPLC). The calculated XDH+XO and XO activity increased from 1.88 and 1.66 microU/mg protein, respectively, before the cross clamp to 3.77 and 3.11 microU/mg, respectively, 7 minutes after reperfusion to the superior mesenteric, celiac, and right renal artery beds. The release of a significant biological source of ROS may explain the damage to lung or heart observed after ischemia to the human liver and intestine.
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PMID:Circulating xanthine oxidase in human ischemia reperfusion. 771 6

Oxygen radicals have been proposed to be involved in the induction of liver cell damage during reperfusion after ischemia. The role of xanthine oxidase in this process and the potential of the antioxidant system have been studied in a model of in vivo ischemia of rat liver followed by 1 h reperfusion by the use of enzyme histochemistry. Based on decreased lactate dehydrogenase activity in certain areas of liver parenchyma, cell damage could already be detected at 1 h reperfusion after ischemia. Incubations performed on serial sections showed that the same areas contained decreased activities of xanthine oxidoreductase, xanthine oxidase, catalase and glucose-6-phosphate dehydrogenase. Some individual cells in the undamaged liver parenchyma expressed a very high glucose-6-phosphate dehydrogenase, which suggests that these cells have a good defence against oxidative stress. It is concluded that oxygen radicals derived from xanthine oxidase do not play a decisive role in the induction of cell damage immediately at reperfusion after ischemia. However, it cannot be excluded that xanthine oxidase present in the blood stream can give rise to the development of additional damage later on.
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PMID:The role of xanthine oxidase in ischemia/reperfusion damage of rat liver. 775 31

To assess right colic artery blood flow and relevance of xanthine dehydrogenase/xanthine oxidase after experimentally induced strangulation obstruction and reperfusion of the colon, 5 ponies were subjected to 2.5 hours of complete ischemia of the left dorsal and ventral colons, allowed to recover from surgery, and monitored during a 48-hour reperfusion period. Five ponies were subjected to sham surgery and served as controls. All ponies had a Doppler ultrasound blood flow monitor implanted on the right colic artery near the pelvic flexure 10 to 14 days prior to the ischemic period. Colic artery blood flow was monitored prior to, during, and for 4 hours after surgery. Blood samples from the right colic artery and vein distal to the obstruction site were collected during surgery (prior to ischemia, after 1 and 2 hours of ischemia, and after 10 and 60 minutes of reperfusion) for determination of arterial and venous blood gas tensions and electrolytes. Prior to surgery, blood selenium and plasma vitamin E (alpha-tocopherol) concentrations and blood glutathione peroxidase (GPX) activity were determined to assess the status of endogenous antioxidants. Combined xanthine dehydrogenase (XDH) plus xanthine oxidase (XO) activity, and XO activity alone (nanomoles per minute per gram of tissue) were determined, using a dual-spectrophotometric technique. Xanthine dehydrogenase and oxidase activities were determined prior to ischemia, after 1 and 2 hours of ischemia, and at 1 and 48 hours after reperfusion. Median blood flow in the experimental and control groups (156 ml/min and 110 ml/min, respectively) was not statistically different before surgery, and was significantly (P < 0.02) lower in the experimental (4 ml/min) vs the control group (72.5 ml/min) during the ischemic period. Experimental ponies had significantly (P < 0.03) lower right colic artery blood flow during the 4 hours immediately after recovery from anesthesia. Significant difference was not observed in right colonic venous bicarbonate concentration between groups at any time. Median right colonic venous PCO2, pH, and standard base excess were different (P < 0.001) between groups during the ischemic period only. Median venous oxygen saturation and median venous PO2 were significantly (P < 0.001) lower in the experimental ponies at the end of 2 hours of ischemia, but were significantly (P < 0.05) increased during the reperfusion phase. Median venous potassium concentration was significantly (P < 0.01) higher in experimental ponies during the ischemic and reperfusion phases. Vitamin E and GPX values were within normal limits for all ponies.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Measurements of blood flow and xanthine oxidase activity during postischemic reperfusion of the large colon of ponies. 797 59

It has been widely postulated that the central mechanism of hepatic reperfusion injury involves the conversion, during ischemia, of the enzyme xanthine dehydrogenase (XDH) to its free radical-producing form, xanthine oxidase (XOD). However, this theory has been questioned because (a) XDH to XOD conversion in whole liver occurs very slowly; (b) the cellular distribution of XDH/XOD is unclear; and (c) the direct demonstration of XDH to XOD conversion in viable cells is lacking. In this paper, we address all three issues by measuring XDH to XOD conversion and cell viability in purified populations of hepatic endothelial cells (EC), Kupffer cells (KC), and hepatocytes (HEP). Although XDH/XOD activity on a cellular basis was greater in hepatocytes (0.92 +/- 0.12 mU/10(6) cells) than ECs (0.03 +/- 0.01) or KCs (0.12 +/- 0.04), XDH + XOD specific activity was similar in all three cell types (HEP 1.85 +/- 0.10 U/g protein; EC 1.69 +/- 0.54; KC 2.30 +/- 0.22). Over 150 min of warm (37 degrees C) or 24 h of cold (4 degrees C) hypoxia, percent XOD activity increased slowly in ECs, from 21 +/- 2% (basal) to 39 +/- 3% (warm) and 49 +/- 5% (cold) and in HEPs (29 +/- 2% to 38 +/- 3% and 49 +/- 2%), but converted significantly faster in KCs (28 +/- 3% to 91 +/- 7% and 94 +/- 4%). The dramatic changes in Kupffer cell XOD during cold hypoxia occurred despite only minor changes in cell viability. When hypoxic KCs were reoxygenated after 16 h of cold hypoxia, there was a marked increase in cell death that was significantly blocked by allopurinol. These data suggest that significant conversion to the free radical-producing state occurs within viable KCs, and that Kupffer cell XOD may play an important role in mediating reperfusion injury in the liver.
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PMID:Rapid conversion to high xanthine oxidase activity in viable Kupffer cells during hypoxia. 798 78

Cardiopulmonary and other organ dysfunction often occurs after operation on the descending thoracic aorta. Though there are multiple causes of organ dysfunction in this setting, free radical injury may play a prominent role. Xanthine oxidoreductase, an enzyme that generates oxidants after exposure to ischemia, could be released from ischemic liver and intestine during reperfusion. To test this hypothesis, we created aortic occlusion in eight rabbits for 40 minutes by inflation of a 4F Fogarty balloon catheter in the descending thoracic aorta. Eight sham-operated rabbits served as a control group. Two hours of reperfusion followed removal of the balloon catheter. Hemodynamic and acid-base status were maintained near baseline values during reperfusion. Plasma samples were obtained for determination of the activity of the hepatocellular enzymes xanthine oxidoreductase, aspartate aminotransferase, alanine transferase, and lactate dehydrogenase. Plasma xanthine oxidoreductase activity increased significantly (p < 0.001) during reperfusion (729 +/- 140 microU/ml, mean +/- standard error of the mean) compared with baseline (132 +/- 18 microM/mL). The other enzymes followed a similar pattern of release. We report the release of xanthine oxidoreductase in an animal model that simulates the situation of human thoracic aorta operations. The oxidants produced by the circulating xanthine oxidoreductase observed during reperfusion would likely be toxic to vascular endothelium, potentially contributing to multiple organ dysfunction.
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PMID:Xanthine oxidoreductase release after descending thoracic aorta occlusion and reperfusion in rabbits. 817 64

The aim of this study was to test whether conversion of xanthine dehydrogenase into xanthine oxidase as induced by fasting, ischemia of the liver or both is an in vivo process or only occurs in vitro in homogenates. For this purpose, the conversion rate of xanthine dehydrogenase into xanthine oxidase was studied in liver homogenates obtained from rats after normal feeding or 24 hr of fasting followed or not by 2 hr of ischemia of the liver. In fed rats, the conversion rate of xanthine dehydrogenase into xanthine oxidase was studied as well in liver homogenates after different periods of reperfusion after 2 hr of ischemia. Homogenization was carried out under strictly controlled conditions, after which the supernatants were incubated at 37 degrees C in buffer for 0 to 5 hr. Enzyme activities were assayed spectrophotometrically by measuring urate production at 295 nm. Conversion started only after 2 to 3 hr of incubation of supernatants of control fed livers, whereas conversion started immediately after 24 hr of fasting. The percentage oxidase activity of total xanthine oxidoreductase activity in ischemic livers from fed animals was slightly higher (26.7% +/- 1.7%; p < 0.05) than in control livers (19.3% +/- 1.4%), whereas the percent oxidase activity in ischemic livers from fasted animals (16.7% +/- 1.0%) was not different from that in control animals (16.8% +/- 1.1%). Ischemia for 2 hr caused in vitro a substantial increase in the conversion rate in supernatants of livers of fed and fasted rats as compared with their controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Conversion of xanthine dehydrogenase into xanthine oxidase in rat liver and plasma at the onset of reperfusion after ischemia. 776 24


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