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)

Alterations which occur during ischemia are reviewed. They modify the metabolic status in such a way they prepare the cell to an anomalous response to reoxygenation. The consequence of this disturbance is the generation of oxygen free radicals through several mechanisms, including the mitochondrial oxidative phosphorylation, the arachidonic acid cascade, the activation of xanthine oxidase, activation of phagocytes, iron mobilization, etc. Reduced glutathione is exhausted, proteins are inactivated. Lipid peroxidation induces membrane breakdown and cellular death.
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PMID:Ischemia, reperfusion and oxygen free radicals. 129 Jun 47

Plasmodium knowlesi (a simian malarial parasite) infection resulted in elevation of hepatic oxidative stress in monkeys. Further, the antioxidant defence system of the host was also noticeably affected. The infected monkeys showed a marked increase in the levels of superoxide (O2-), lipid peroxidation (LPO), glutathione (GSH) and xanthine oxidase (XO), and decreased levels of superoxide dismutase (SOD) and catalase. Oral administration of chloroquine (20 mg kg body wt-1 for 3 days) to infected monkeys caused recovery trends in oxidative stress and antioxidant defences to almost normal a week after cessation of drug treatment.
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PMID:Status of oxidative stress and antioxidant defences during Plasmodium knowlesi infection and chloroquine treatment in Macaca mulatta. 131 84

Three factorial experiments were conducted to determine if high dietary fluoride (F) would inhibit selenite toxicity in rats. Initially, three levels of selenite (0.05, 3, and 5 mg/kg diet) were matched against three levels of F (2, 75, and 150 mg/kg diet). Fluoride failed to prevent the depressive effect of selenite on 8-wk food intake and body wt gain. Selenium (Se) concentration of plasma and kidney and enzymatic activity of whole blood glutathione peroxidase (GSH-Px) were also unaffected by F. Liver Se concentration, however, was slightly (12%) but significantly (p < 0.025) reduced when the highest F and Se levels were combined. Fluoride (150 mg/kg) appeared to reduce liver selenite toxicity (5 mg/kg). Therefore, further study focused on liver histology with treatments that eliminated the middle levels of selenite and F. Fluoride prevented the hepatic necrosis seen in selenite-toxic rats. Similar histological lesions were not observed for kidney or heart. Fluoride partially (26%) but significantly (p < 0.025) reduced thiobarbituric-reactive substances in selenite-toxic rats, but there was no F effect on intracellular distribution of liver Se, glutathione levels in liver and kidney, or on liver xanthine oxidase activity. Overall, the protective effect of F on selenite toxicity appears to be confined to liver pathology. The exact mechanism for this effect, however, remains unclear.
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PMID:Effect of dietary fluoride on selenite toxicity in the rat. 138 17

Changes of antioxidant activity of dalargin in the liver after naloxone (100 micrograms/kg) administration were examined in experiment on 144 rats with cholestasis. It was found that dalargin inhibited the activity of xanthine oxidase by 32-37% in different time periods after the injection. Dalargin and naloxone, when used in combination, had no effect on the enzyme activity. Glutathione-S-transferase activity rose by 38.0% and 21.8% on hour 1 and 3 after the injection, respectively, while simultaneous injection of dalargin and naloxone induced no changes in the enzyme activity after 1 hour, though decreased it by 36.8% and 26.4% on hour 3 and 5, respectively. Dalargin inhibited lipid peroxidation by 29-35%, simultaneous injection of dalargin and naloxone raised lipid peroxidation by 109.2%, 80.7% and 25.7% after 1, 3 and 5 hours, respectively. Dalargin injection elucidated a marked tendency to lowering of blood release of the liver-specific enzymes histidase and urokaninase in line with enhancement of their activity in the liver. A combined injection of dalargin and naloxone promoted high release of histidase and urokaninase in blood and did not change histidase activity in the liver in all cases. Urokanidase activity elevated in 5 hours. It was noticed that dalargin raised leu-enkephalin levels in the liver 3.5-fold 1 h after the injection. The reduced dalargin antioxidant effect coupled with naloxone pretreatment demonstrated indirect action of the neuropeptide on the liver via neuron receptors of the liver.
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PMID:[Molecular mechanisms of antioxidant action of dalargin on the liver in experimental cholestasis]. 139 60

After 60 min of reperfusion following 60 min of ischemia, the ischemia-induced decrease in liver tissue adenosine triphosphate (ATP) concentration had recovered by 66%, and full recovery of mitochondrial function--that is, the respiratory control index (RCI) and the rate of oxygen consumption in state-III respiration (ST III O2)--was observed. In contrast, liver tissue ATP concentration had recovered by only 13%, and marked low RCI and ST III O2 were observed after 60 min of reperfusion following 180 min of ischemia. Intermediate results were observed in rats after 60 min of reperfusion following 120 min of ischemia. Liver tissue hypoxanthine and xanthine, substrates of xanthine oxidase, increased ischemic time dependently. Liver tissue concentrations of the reduced form of glutathione (GSH) and the oxidized form of glutathione (GSSG) and activities of glutathione peroxidase and glutathione reductase did not change after 60 min of reperfusion following 60 min of ischemia. In contrast, GSH concentration and glutathione peroxidase activity decreased significantly after 60 min of reperfusion following 180 min of ischemia. Since the glutathione redox system is an important contributor to the scavenging of free radicals after reperfusion following a long time of ischemia, the free radical scavenging ability might decrease in spite of enhancement of free radical generation, which might play an important role in the inhibition of the recovery of tissue ATP concentrations and mitochondrial function.
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PMID:Changes in the glutathione redox system during ischemia and reperfusion in rat liver. 143 57

We studied the effect of inhibition of oxyradical formation and of endogenous glutathione (GSH) depletion on lesion formation in the gastrointestinal tract in a modified rat hemorrhagic shock model (1 h hypotension and 1 h reperfusion). Allopurinol, an inhibitor of xanthine oxidase, did not protect against lesion formation. This suggests that oxygen radicals generated from xanthine oxidase may not be the major cause of injury under these conditions of prolonged 'ischemia'-reperfusion. Phorone (diisopropylideneacetone), a GSH depletor, decreased mucosal GSH levels in the corpus, duodenum and small intestine, and also significantly reduced lesion formation histologically in the corpus, antrum, duodenum and small intestine. However, there was no significant differences in mucosal blood flow (as estimated by changes in mucosal hemoglobin concentrations and oxygen saturation of mucosal hemoglobin) in the corpus, antrum, duodenum and small intestine between phorone-pretreated and control rats. We conclude that phorone decreased mucosal GSH concentrations and exerted a protective effect against hemorrhagic shock-induced gastrointestinal mucosal lesions. The protective effect appears to be independent of mucosal blood flow.
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PMID:Effect of phorone and allopurinol on ischemia-reperfusion injury in gastrointestinal mucosa of the rat. 150 63

We examined the effects of tumor necrosis factor-alpha (TNF alpha) stimulation of endothelial cells on the increase in endothelial permeability induced by H2O2. Bovine pulmonary microvascular endothelial cells (BPMVEC) were grown to confluence on a microporous filter and the 125I-albumin clearance rate across the monolayer was determined. Pretreatment with TNF alpha (100 U/ml) for 6 h had no direct effect on transendothelial 125I-albumin permeability. However, TNF alpha pretreatment enhanced the susceptibility of BPMVEC to H2O2; that is, H2O2 (10 microM) alone had no direct effect, whereas H2O2 increased 125I-albumin permeability more than threefold when added to monolayers pretreated for 6 h with TNF alpha. Determination of lactate dehydrogenase release indicated that increased permeability was not due to cytolysis. We measured the intracellular contents of GSH and catalase to determine their possible role in mediating the increased susceptibility to H2O2. TNF alpha treatment (100 U/ml for 6 h) decreased total GSH content and concomitantly increased the oxidized GSH content, but did not alter the cellular catalase activity. The role of GSH was examined by pretreating endothelial cells with 2 mM GSH for 3 h, which produced an 80% increase in intracellular GSH content. GSH repletion inhibited the increased sensitivity of the TNF alpha-treated endothelial cells to H2O2. We tested the effects of xanthine oxidase (XO) inhibition since XO activation may be a source of oxidants responsible for the decrease in cellular GSH content. Pretreatment with 0.5 mM oxypurinol attenuated the synergistic effect of TNF alpha and H2O2 on endothelial permeability. The results indicate that decreased oxidant buffering capacity secondary to TNF alpha-induced reduction in intracellular GSH content mediates the increased susceptibility of endothelial cells to H2O2. This mechanism may contribute to oxidant-dependent vascular endothelial injury in septicemia associated with TNF alpha release.
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PMID:Tumor necrosis factor-alpha-mediated decrease in glutathione increases the sensitivity of pulmonary vascular endothelial cells to H2O2. 154 73

Heat-induced hepatotoxicity accompanying hyperthermic liver perfusion was studied in the isolated, haemoglobin-free perfused rat liver. Trypan blue uptake, a sensitive indicator of cell death, was used to examine the relationship between the efflux of oxidized glutathione (oxidative stress), the appearance of cytosolic enzymes in the perfusate and cell death. Livers were perfused at 37, 42, 42.5 and 43 degrees C. The efflux of total glutathione (GSH) and oxidized glutathione (GSSG) increased with time and temperature. Differences between temperature groups were significant for both parameters for 37 versus 42, 42.5 and 43 degrees C (p less than 0.05). Temperature-related differences in GSH levels appeared at 15 min for 37 versus 42 degrees C and in GSSG levels at 30 min for 37 versus 42 and 42.5 degrees C. Biliary excretion of total GSH increased from 72 nmol at 37 degrees C to 144 nmol at 42 degrees C, 160 nmol at 42.5 degrees C and 124 nmol at 43 degrees C, which was significant for 37 versus 42 and 42.5 degrees C (p less than 0.05). The release of allantoin into the perfusate, a measure of purine catabolism and flux through xanthine oxidase, was increased at 42, 42.5 and 43 degrees C compared to 37 degrees C (p less than 0.05). Liver injury was assessed by measuring the release of asportate aminotransferase (AST) and lactate dehydrogenase (LDH) and uptake of trypan blue after perfusion at each temperature. There was a pronounced release of LDH and AST into the perfusate after 60 min of perfusion at 42, 42.5 and 43 degrees C, the levels of which were significantly different from the 37 degrees C mean level. There was no uptake of trypan blue after 60 min perfusion at 37 degrees C. Perfusion at 42, 42.5 and 43 degrees C resulted in the uptake of trypan blue in the pericentral areas, but the dye uptake was significant (p less than 0.05) compared to 37 degrees C at 42.5 and 43 degrees C only. These data show that heat-induced pericentral cell death is minimal after 60 min at 42-43 degrees C, and that the biochemical process which occurred during this period suggest 'oxidative stress' as a causative factor in hyperthermic hepatotoxicity. In addition, this liver toxicity is probably related to xanthine oxidase activity or the depletion of GSH as the initiating event which leads to lipid peroxidation and cellular damage.
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PMID:Oxidative stress as a precursor to the irreversible hepatocellular injury caused by hyperthermia. 194 May 10

The in vitro conversion of (+)-3,4-methylenedioxymethamphetamine and (-)-3,4-methylenedioxymethamphetamine to the corresponding catecholamine, 3,4-dihydroxymethamphetamine (N-methyl-alpha-methyldopamine), by rat liver microsomes was examined. Metabolite formation was monitored after short-term incubations using high-performance liquid chromatography-electrochemical detection to determine concentrations of the catecholamine. The formation of N-methyl-alpha-methyldopamine exhibited enantioselectivity and levels were significantly higher after incubation of the (+)-isomer. The reaction appears to be cytochrome P-450 dependent as it was sensitive to SKF 525A and carbon monoxide. The catecholamine was unstable and was metabolized rapidly to a compound capable of forming an adduct with glutathione (GSH) and other thiol compounds. This second oxidation did not appear to be cytochrome P-450-dependent but required NADPH and microsomal protein. Catecholamine oxidation was inhibited by superoxide dismutase and by reducing agents. The same catecholamine oxidation product, characterized as the GSH adduct, could be generated by a xanthine-xanthine oxidase mixture and by tyrosinase. Mass spectral data showed that it was a 1:1 amine GSH adduct. These results indicate that MDMA is oxidized by cytochrome P-450 to the catechol and the catecholamine oxidized by superoxide to a quinone to which GSH or other thiol functions add. The formation of this quinone and its thiol adducts may account for some of the irreversible actions of this compound on serotonergic neurons.
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PMID:Metabolism of methylenedioxymethamphetamine: formation of dihydroxymethamphetamine and a quinone identified as its glutathione adduct. 197 41

Reactive O2 species appear to be generated both during hypoxia and at reoxygenation, but it has not been established whether these species interact with heart tissue and cause injury. Oxidative changes were evaluated in isolated rat heart perfused with Krebs-Henseleit medium containing 10 mM glucose and 2.5 mM calcium. After 5-10 min hypoxia, tissue glutathione (GSH) decreased while glutathione disulfide (GSSG), protein carbonyls, and thiobarbituric acid reactive substances (TBARS) increased compared with controls. Similarly, sarcolemmal and sarcoplasmic reticular Ca-ATPase activity (an enzyme susceptible to oxidative inactivation) decreased in response to 10 min hypoxia. These changes were more pronounced after 60 min of hypoxia when protein-GSH mixed disulfides were also increased. There were no further oxidative changes after 4 min reoxygenation when the release of lactate dehydrogenase (LDH) was maximal. Myocardial protein thiol and alpha-tocopherol contents were not significantly changed by either hypoxia or reoxygenation. Mitochondria also exhibited oxidative changes but with more pronounced increases in GSSG and mixed disulfides. There was no change in GSH or GSSG efflux into the coronary effluent during hypoxia, although, in parallel with LDH release, both increased after reoxygenation. Diamide (200 microM), t-butylhydroperoxide (20 microM), or purine (2.3 mM) + xanthine oxidase (0.01 U/ml) were infused for 10 min. Except for large diamide-induced changes in protein thiols and mixed disulfides, the magnitude of the changes produced by these oxidants was similar to those produced by hypoxia. These data show that changes consistent with oxidative processes occur in whole heart and mitochondria in response to hypoxia. The absence of marked signs of oxidation at reoxygenation suggest that enzyme release at this time is unrelated to oxidative stress.
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PMID:Oxidative changes in hypoxic rat heart tissue. 203 61


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