Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperpermeability is the crux of pathogenesis of sudden lung edema in many pulmonary disorders, especially in acute lung injury and acute respiratory distress syndrome (ARDS). Using our modified method for assessment of pulmonary vascular permeability, we observed the effects of xanthine with xanthine oxidase (X-XO) perfused in rat pulmonary artery and the protection of vasoactive intestinal polypeptide (VIP) against the injury of pulmonary vascular permeability. After addition of xanthine oxidase in the perfusate reservoir containing xanthine, 125I-albumin leak index (125I-ALI) was remarkably increased while peak airway pressure (Paw) showed no significant increase, and perfusion pressure of pulmonary artery (Ppa) and lung wet/dry weight ratio (W/D) were only slightly increased. Xanthine plus xanthine oxidase also increased thromboxane B2 (TX B2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) in the perfusate. Treatment with VIP obviously reduced or totally prevented all signs of injury. Simultaneously, VIP also diminished or abolished the associated generation of arachidonate products. The results indicated that VIP has potent protective activity against injury of pulmonary vascular permeability and may be a physiological modulator of inflammatory damage to vascular endothelium associated with toxic oxygen metabolites.
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PMID:[Vasoactive intestinal polypeptide prevents injury of pulmonary vascular permeability due to xanthine with xanthine oxidase]. 857 46

Hyperpermeability is a crux of pathogenesis of sudden lung edema in many pulmonary disorders, especially in acute lung injury and adult respiratory distress syndrome (ARDS). Using our modified method for assessment of pulmonary vascular permeability, we observed the effects of xanthine with xanthine oxidase (X-XO) perfused in rat pulmonary artery and the protection of vasoactive intestinal polypeptide (VIP) against the injury of pulmonary vascular permeability. After addition of xanthine oxidase in the perfusate reservoir containing xanthine, 125I-albumin leak index (125IALI) was remarkably increased while peak airway pressure (Paw) was not significantly increased, and perfusion pressure of pulmonary artery (Ppa) and lung wet/dry weight ratio (W/D) were only slightly increased. Xanthine plus xanthine oxidase also increased thromboxane B2 (TX B2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) in the perfusate. Treatment with VIP obviously reduced or totally prevented all signs of injury. Simultaneously, VIP also diminished or abolished the associated generation of arachidonate products. The results indicated that VIP has potent protective activity against injury of pulmonary vascular permeability and may be a physiological modulator of inflammatory damage to vascular endothelium associated with toxic oxygen metabolites.
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PMID:Vasoactive intestinal polypeptide prevents injury of pulmonary vascular permeability due to xanthine with xanthine oxidase. 858 Apr 82

The influence of endogenous cell .NO production and .NO derived from exogenous sources on oxidant injury to cultured fetal rat lung alveolar epithelium and an animal model of pulmonary oxidant injury was examined. Confluent fetal rat alveolar epithelial cell monolayers were stimulated to produce .NO after treatment with a combination of cytokines (IL-1 beta, TNF-alpha, IFN-gamma), LPS and zymosan-activated serum (CZ). Cell injury, assessed by 14C-adenine release, was significantly increased compared to basal and CZ-induced cells after inhibition of .NO synthesis by L-NMMA. Cell monolayer macromolecule barrier function was determined by the rate of diffusion of 125I-albumin from the apical to basolateral side of monolayers. Following exposure to CZ and/or O2.- generated by xanthine oxidase + lumazine (XO), endogenous cell .NO production and exogenously administered .NO (from .NO donors S-nitrosyl-glutathione and S-nitroso-N-acetylpenicillamine) significantly inhibited the increased monolayer permeability induced by exposure to reactive oxygen species. Furthermore, inhalation of 5-10 ppm of .NO significantly reduced the toxicity of > 95% oxygen to adult rats. We conclude that when cultured pulmonary epithelial cells and lung tissue in vivo are subjected to inflammatory mediators or acute oxidative stress, .NO can play a protective role by inhibiting O2.(-)-dependent toxicity.
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PMID:Nitric oxide regulation of superoxide-dependent lung injury: oxidant-protective actions of endogenously produced and exogenously administered nitric oxide. 879 Oct 92

Inhaled nitric oxide (NO) may modify surfactant either by interacting with the surfactant complex or by changing the capacity of the proteins of the epithelial lining fluid to inhibit the surface activity. Natural surfactant was exposed to NO (80 parts/million) in air in vitro while the gas-liquid surface was cycled. In the presence or absence of oxidants (Fe2+, xanthine, xanthine oxidase), surfactant exposed to NO retained the high surface activity significantly better than control surfactants exposed to air. Two surfactant inhibitors, hemoglobin (Hb) and albumin, were separately exposed to NO. In contrast to albumin, NO-exposed Hb and methemoglobin (MetHb; 16-125 micrograms/ml) decreased the surface activity at low surfactant concentrations, whereas native Hb had no effect. Surfactant recovered by sedimentation after exposure to MetHb had decreased surface activity and contained MetHb, whereas Hb did not bind to surfactant. Acidic phospholipid phosphatidylglycerol increased the binding of MetHb to surfactant. The MetHb-induced decrease in surface activity was elicited in the presence of surfactant proteins, including a peptide mimicking surfactant protein B. MetHb (but not Hb) added to a low dose of exogenous surfactant decreased the efficacy of surfactant to improve the lung compliance of premature rabbits. We propose that inhaled NO promotes the surface activity of surfactant during tidal ventilation and that, in high-permeability lung edema and surfactant deficiency, inhaled NO increases the inhibition of surface activity by converting Hb to MetHb in the alveolar space.
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PMID:A mechanism of nitric oxide-induced surfactant dysfunction. 880 11

To prevent oxidative tissue damage induced by strenuous exercise in the liver and kidney superoxide dismutase derivative (SM-SOD), which circulated bound to albumin with a half-life of 6 h, was injected intraperitoneally into rats. Exhausting treadmill running caused a significant increase in the activities of xanthine oxidase (XO), and glutathione peroxidase (GPX) in addition to concentrations of thiobarbituric acid-reactive substances (TBARS) in hepatic tissue immediately after running. There was a definite increase in the immunoreactive content of mitochondrial superoxide dismutase (Mn-SOD) 1 day after the running. Meanwhile, the TBARS concentration in the kidney was markedly elevated 3 days after running. The activities of GPX, and catalase in the kidney increased significantly immediately and on days 1 and 3 following the test. The immunoreactive content of Mn-SOD also increased 1 day after running. The exercise induced no significant changes in immunoreactive Cu, Zn-SOD content in either tissue. The administration of SM-SOD provided effective protection against lipid peroxidation, and significantly attenuated the alterations in XO and all the anti-oxidant enzymes, measured. In summary, the present data would suggest that exhausting exercise may induce XO-derived oxidative damage in the liver, while the increase in lipid peroxidation in the kidney might be the result of washout-dependent accumulation of peroxidised metabolites. We found that the administration of SM-SOD provided excellent protection against exercise-induced oxidative stress in both liver and kidney.
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PMID:Superoxide dismutase derivative prevents oxidative damage in liver and kidney of rats induced by exhausting exercise. 882 Aug 84

Mixed ligand complexes of copper polyamine with biomolecules such as imidazole, substituted imidazoles or pyridine have been synthesized and characterized. These molecules were used because of their low toxicity and high activity. These complexes were found to possess a distorted octahedral microenvironment with a potential SOD mimicking activity. The IC50 values for these complexes were of the order of 2-90 microM. Pyridine and imidazole complexes were most effective as they possess the lowest IC50 values of 2.1 and 6 microM respectively which are higher than the IC50 value of polyamine copper complex. Based on the uric acid estimations, it has also been ascertained that these complexes dismute O2- without inhibiting xanthine oxidase activity. The presence of increasing concentrations of albumin had no effect on the SOD mimicking activity of mixed ligand complexes. Polyamine complex, however lost approximately 80% of SOD mimicking activity in the presence of albumin (1 mg). These results suggest that coordination of polyamine copper complex with imidazoles/pyridine may abolish their binding affinity for albumin while potentiating their SOD mimicking activity.
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PMID:Coordination of copperpolyamine complex with imidazoles potentiates it superoxide dismutase mimicking activity and abolishes its interaction with albumin. 884 51

Increased vascular permeability to plasma proteins and altered hemodynamics at the site of inflammation are characteristics of inflammation. In the present study, alterations in endothelial barrier permeability were evaluated in different organs/tissues 6 h after a systemic inflammatory response induced by intravenous injection of bradykinin (BK; 1.7 mg/kg). The effect of intravenous pretreatment with indomethacin or ibuprofen (cyclooxygenase inhibitors), N-acetyl-L-cysteine (NAC, an oxygen free radical scavenger), and allopurinol (a xanthine oxidase inhibitor) was determined. Endothelial permeability was evaluated by determining tissue water content (TWC), 125I-labeled human serum albumin (HSA) flux, and albumin leakage index (ALI) in various organs/tissues. The vasodilation in the local tissues was reflected by tissue blood content (TBC), measured by 51Cr-labeled red blood cells. The results indicate that albumin flux significantly increased in the peritoneum, pancreas, stomach, PSI, DSI, colon, kidneys, liver, lungs, and brain, TBC significantly increased in the kidneys, liver, lungs, and heart, as well as in the intestine, and an increased ALI, assaying endothelial permeability considering local hemodynamic alterations was noted in the pancreas, kidneys, liver, lungs, PSI, and DSI in the group with BK alone. These changes were to varying degrees reversed by pretreatment with indomethacin, ibuprofen, N-acetyl-L-cysteine, or allopurinol, where the protective effect tended to be organ-dependent.
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PMID:Influence of anti-inflammatory and antioxidant agents on endothelial permeability alterations induced by bradykinin. 895 57

The objective of this study was to define the role of oxidants and lipid mediators in the leukocyte-endothelial cell adhesion and albumin leakage elicited in rat mesenteric venules by ischemia-reperfusion (I/R). Intravital fluorescence microscopy was used to monitor leukocyte adherence and emigration, platelet-leukocyte aggregation, mast cell degranulation, and albumin leakage after release of a 20-min arterial occlusion. I/R elicited large increases in leukocyte-endothelial cell adhesion and albumin leakage. These responses were significantly attenuated in venules treated with either superoxide dismutase, oxypurinol (an inhibitor of xanthine oxidase), lodoxamide (a mast cell stabilizer), WEB-2086 (a platelet-activating factor antagonist), or SC-41930 (a leukotriene B4-receptor antagonist) but not by U-74006F (an inhibitor of lipid peroxidation). Platelet-leukocyte aggregates and mast cell degranulation induced by I/R were also attenuated by administration of either superoxide dismutase or lodoxamide. These results support the hypothesis that oxidants produced, in part, by xanthine oxidase promote the formation (by mast cells and endothelial cells) of platelet-activating factor and leukotriene B4, which recruit and activate leukocytes in postischemic venules. The adherent and emigrated leukocytes then mediate the increased albumin extravasation observed in the postcapillary venules.
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PMID:Ischemia/reperfusion-induced microvascular dysfunction: role of oxidants and lipid mediators. 922 76

Among progeny of a hybrid (Rana shqiperica x R. lessonae) x R. lessonae, 14 of 22 loci form four linkage groups (LGs): (1) mitochondrial aspartate aminotransferase, carbonate dehydratase-2, esterase 4, peptidase D; (2) mannosephosphate isomerase, lactate dehydrogenase-B, sex, hexokinase-1, peptidase B; (3) albumin, fructose-biphosphatase-1, guanine deaminase; (4) mitochondrial superoxide dismutase, cytosolic malic enzyme, xanthine oxidase. Fructose-biphosphate aldolase-2 and cytosolic aspartate aminotransferase possibly form a fifth LG. Mitochondrial aconitate hydratase, alpha-glucosidase, glyceraldehyde-3-phosphate dehydrogenase, phosphogluconate dehydrogenase, and phosphoglucomutase-2 are unlinked to other loci. All testable linkages (among eight loci of LGs 1, 2, 3, and 4) are shared with eastern palearctic water frogs. Including published data, 44 protein loci can be assigned to 10 of the 13 chromosomes in Holarctic Rana. Of testable pairs among 18 protein loci, agreement between Palearctic and Nearctic Rana is complete (125 unlinked, 14 linked pairs among 14 loci of five syntenies), and Holarctic Rana and Xenopus laevis are highly concordant (125 shared nonlinkages, 13 shared linkages, three differences). Several Rana syntenies occur in mammals and fish. Many syntenies apparently have persisted for 60-140 x 10(6) years (frogs), some even for 350-400 x 10(6) years (mammals and teleosts).
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PMID:Linkage groups of protein-coding genes in western palearctic water frogs reveal extensive evolutionary conservation. 928 85

8-(3-Methoxy-4-phenylsulfinylphenyl) pyrazolo[1,5-a]-1,3,5-triazine-4(1H)-one (BOF-4272) blocks xanthine oxidase/xanthine dehydrogenase in the liver. BOF-4272 with a sulfoxide chiral center includes R(+)- and S(-)-enantiomers. The enantioselectivity in the global disposition of BOF-4272 can be attributed to that in the local disposition of organs, especially the liver. Thus, the enantioselectivity in the hepatic local disposition of BOF-4272 was compared between R- and S-enantiomers by a hepatic perfusion experiment with a pulse input into the portal vein. The influence of perfusate albumin on the enantioselective local disposition was also investigated. The elution time profile of each BOF-4272 enantiomer from the liver into the hepatic vein was measured at four different bovine serum albumin (BSA) concentrations (0, 0.25, 1.0 and 4.0%) in the perfusate at 37 and 4 degrees C. A crossover test was carried out for R- and S-enantiomers using one rat liver. In the absence of perfusate BSA at 37 degrees C, hepatic extraction ratios (E[H]) of R- and S-enantiomers of BOF-4272 were 75.6 +/- 4.3% and 71.7 +/- 3.3%, respectively, which were statistically the same. In the presence of 4.0% BSA at 37 degrees C, E(H) values of R- and S-enantiomers were 31.7 +/- 4.6% and 19.6 +/- 3.8%, respectively, which demonstrated that E(H) of R-enantiomer was significantly greater than that of S-enantiomer (p < 0.001). In the absence and presence of perfusate BSA at 4 degrees C, there was no significant difference in E(H) between S- and R-enantiomers. An amplification of stereoselectivity with albumin was observed by the perfusion experiment using BOF-4272 enantiomers.
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PMID:Influence of albumin on enantioselective local disposition of BOF-4272, a xanthine oxidase inhibitor with chiral sulfoxide, in rat liver. 944 5


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