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)

The metabolic function of the lungs may be impaired in acute lung injuries. The present work examined the effect of toxic oxygen metabolites (TOM) on the pulmonary clearance of prostaglandin E2 (PGE2). Isolated rat lungs perfused with plasma were exposed to TOM, generated by xanthine oxidase (XO) and hypoxanthine (HX) in the perfusate. Inactivation of PGE2 was determined by superfusion bioassay technique. XO and HX (n = 6) reduced the inactivation of PGE2 from 78 +/- 4% (mean +/- SE) to 61 +/- 3%. This reduction was inhibited by the free radical scavengers superoxide dismutase and catalase, as well as by allopurinol, an inhibitor of XO. Neither hydrostatic lung edema nor perfusion per se decreased the inactivation of PGE2. Lungs pretreated with indomethacin still showed impaired PGE2 inactivation after exposure to XO and HX, indicating that a possible release of PGE2-like substances did not influence our findings. This study indicates that TOM may impair pulmonary metabolic function as shown by reduced inactivation of PGE2.
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PMID:Toxic oxygen metabolites reduce inactivation of prostaglandin E2 in isolated perfused rat lungs. 155 17

Effects of toxic oxygen metabolites (TOM) on the pulmonary vascular bed and airways were studied in isolated, plasma-perfused rat lungs. TOM were generated by xanthine oxidase (XO) (0.1 or 0.25 unit.ml-1) and hypoxanthine (HX) (1 mol.l-1). In vitro measurements by chemiluminescence indicated that the major oxygen metabolite generated by XO and HX was H2O2. Measurements of PO2 in the perfusate as an indicator of O2-consumption suggested that production of TOM by XO and HX was finished within 30 min. XO and HX induced an early dose-dependent bronchoconstriction and a late increase in transpulmonary pressure (Ptp). Pulmonary arterial pressure (Ppa) increased gradually and levelled off within 30 min with low-dose XO, but not with high-dose XO. As judged by weight increase of the lungs, interstitial edema occurred regularly. Allopurinol, an inhibitor of XO, blocked the lung responses caused by XO and HX. Catalase attenuated all lung responses induced by XO and HX, while superoxide dismutase had no effect. The hydroxyl radical scavenger dimethylsulfoxide abolished the increase in Ptp and attenuated the increase in Ppa, but did not consistently protect the lungs from edema development. This study shows that TOM induce vasoconstriction, bronchoconstriction and lung edema in plasma-perfused rat lungs, mainly due to generation of H2O2 and the hydroxyl radical.
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PMID:Toxic oxygen metabolites induce vasoconstriction and bronchoconstriction in isolated, plasma-perfused rat lungs. 200 2

Washed human platelets prevent edema formation in isolated rabbit lungs infused with xanthine oxidase, an enzyme that injures endothelial membranes by generating extracellular oxidants. We hypothesized that platelets would similarly preserve membrane permeability in isolated lungs exposed to ischemia-reperfusion injury, a model that perturbs endothelial cells by the generation of intracellular oxidants. Isolated perfused rabbit lungs (IPL) were exposed to warm ischemia-reperfusion to cause lung edema. The infusion of washed human platelets (1.05 +/- 0.02 x 10(10) cells) prevented edema formation as measured by lung weight gain, wet-to-dry lung weight ratios, histological edema, and preservation of paraendothelial cell tight junctions. Inhibition of the platelet glutathione redox cycle with 1,3-bis(2-chloroethyl)-1-nitrosourea, dehydroepiandrosterone, or 1-chloro-2,4-dinitrobenzene interfered with platelet protective effects. In contrast, inhibition of platelet catalase with aminotriazole and H2O2 had no effect on platelet protection. Lung tissue malonyldialdehyde concentrations were similar in isolated lungs exposed to ischemia-reperfusion with or without the infusion of platelets. These results indicate that platelet attenuation of ischemia-reperfusion lung edema depends on platelet glutathione redox cycle antioxidants but not platelet catalase.
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PMID:Washed human platelets prevent ischemia-reperfusion edema in isolated rabbit lungs. 203 73

Toxic oxygen metabolites (TOM) have been suggested to be mediators of permeability edema associated with the adult respiratory distress syndrome (ARDS). Because corticosteroids have possible beneficial effects in ARDS, we have examined the effect of methylprednisolone (MP) on TOM-induced lung edema in isolated, plasma-perfused rat lungs. TOM were generated by adding xanthine oxidase (XO) and hypoxanthine (HX) to the perfusate. Microvascular permeability was assessed by fluid filtration rate (FFR). FFR was determined before and 30 min after administration of XO and HX by measuring the weight increase of the lungs for the last 3 min during a standard 5 min elevation of the outlet pressure. MP was administered in two different ways: 1) Added to the perfusate 5 or 60 min before XO and HX (0.1 and 1 mg ml-1), and 2) given as pretreatment to the rats 12 and 2 hr before preparation of the lungs (40 mg kg -1). XO and HX significantly increased FFR compared to lungs perfused with untreated plasma. Pretreatment with MP significantly attenuated the increase in FFR caused by XO and HX. Addition of MP to the perfusate also inhibited the effect of TOM. This latter protection occurred irrespective of when MP was added before XO and HX. However, when the highest dose of MP was added 5 min before XO and HX, there was a loss of the protective effect. In summary, this study provides evidence that MP may directly prevent microvascular injury induced by TOM in isolated perfused rat lungs. The effect was dependent on the dose of MP applied, but not on when MP was administered prior to exposure to TOM.
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PMID:Toxic oxygen metabolites increase microvascular permeability in isolated perfused rat lungs: the effect of methylprednisolone. 206 43

The endothelial cells of pulmonary blood vessel play an significant role in lung vessel permeability, especially in acute lung damage and adult respiratory distress syndrome. In this study, bovine pulmonary endothelial cells were isolated, cultured and identified by means of reverse microscopic, scanning electromicroscopic, transmission electro- microscopic and immunofluorescence microscopic observation. Then they were labeled with 51Cr. Hydrogen peroxide (H2O2), H2O2 with catalase, xanthine oxidase (XO) with hypoxanthine (HX), human neutrophil elastase (HNE), cathepsin-G (C-G) and endotoxin (ET) were incubated with the labeled cells for half hour in various experimental groups respectively. The amount of 51Cr in the suspension released from the damaged cells was counted with r-radiometer. The results show that HNE, ET, H2O2 and superoxide anion (the latter is produced from the reaction between XO and HX) could at some degree damage the membrane of endothelial cells, and the inflammatory mediators of human neutrophils might play an important role in the development of pulmonary edema.
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PMID:[Effect of the products released from the activated human neutrophils and endotoxin on bovine pulmonary endothelial cells]. 208 56

The contribution of lung glucose-6-phosphate dehydrogenase (G-6-PD) activity to pulmonary antioxidant defenses was investigated in the isolated perfused rabbit lung using dehydroepiandrosterone (DHEA), a specific steroidal inhibitor of G-6-PD. Infusion of xanthine oxidase (0.002 U/ml) generated moderate lung edema as measured by increased lung weight and lung lavage albumin content. Infusion of DHEA caused an augmentation of xanthine oxidase-induced lung edema. Hydrostatic factors did not participate in the worsened lung edema because mean pulmonary artery pressures were similar in both experimental groups. Incubation of lung tissue in vitro with DHEA demonstrated ablation of tissue G-6-PD activity without decreasing catalase, glutathione peroxidase, or superoxide dismutase activity. It was concluded that DHEA is a specific inhibitor of lung G-6-PD, and that G-6-PD provides an important antioxidant defense mechanism in preventing oxidant-induced lung injury.
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PMID:Inhibition of rabbit lung glucose-6-phosphate dehydrogenase by dehydroepiandrosterone augments oxidant injury. 213 22

Reactive oxygen species are a major cause of damage occurring in ischemic tissue after reperfusion. During reperfusion transitional metals such as iron are required for reactive oxygen species to mediate their major toxic effects. Xanthine oxidase is an important source of reactive oxygen species during ischemia-reperfusion injury, but not in all organs or species. Because cytochrome P-450 enzymes are an important pulmonary source of superoxide anion (O2-.) generation under basal conditions and during hyperoxia, and provide iron catalysts necessary for hydroxyl radical (.OH) formation and propagation of lipid peroxidation, we postulated that cytochrome P-450 might have a potential role in mediating ischemia-reperfusion injury. In this report, we explored the role of cytochrome P-450 enzymes in a rabbit model of reperfusion lung injury. The P-450 inhibitors 8-methoxypsoralen, piperonyl butoxide, and cimetidine markedly decreased lung edema from transvascular fluid flux. Cimetidine prevented the reperfusion-related increase in lung microvascular permeability, as measured by movement of 125I-albumin from the vascular space into lung water and alveolar fluid. P-450 inhibitors also prevented the increase in lung tissue levels of thiobarbituric acid reactive products in the model. P-450 inhibitors did not block enhanced O2-. generation by ischemic reperfused lungs, measured by in vivo reduction of succinylated ferricytochrome c in lung perfusate, but did prevent the increase in non-protein-bound low molecular weight chelates of iron after reperfusion. Thus, cytochrome P-450 enzymes are not likely a major source of enhanced O2-. generation, but serve as an important source of iron in mediating oxidant injury to the rabbit lung during reperfusion. These results suggest an important role of cytochrome P-450 in reperfusion injury to the lung and suggest potential new therapies for the disorder.
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PMID:Role of cytochrome P-450 in reperfusion injury of the rabbit lung. 217 18

Numerous studies suggest that platelets may contribute to preservation of normal endothelial cell permeability in models of lung injury. We have previously shown that washed human platelets prevent xanthine oxidase-induced edema in the isolated perfused lung and that protective mechanisms depend on the platelet glutathione redox cycle. It is uncertain, however, whether platelets preserve endothelial function by reducing toxic oxygen metabolites or by aggregating and releasing endothelial cell supportive factors-an activity that may require the glutathione redox cycle. In this study, we present data demonstrating that platelet prevention of oxidant lung injury occurs independent of platelet aggregation and release. Isolated rabbit lungs perfused with a cell-free medium were instilled with purine (2 mmol/L) and xanthine oxidase (0.003 U/ml) to generate oxidant lung edema. The infusion of washed human platelets (1 x 10(10) cells) prevented lung edema formation as measured by lung weight gain, wet-to-dry lung weight ratios, and lung histology. Incubation of platelets with prostaglandin E1 (PGE1), a potent inhibitor of platelet aggregation and release, did not inhibit platelet attenuation of lung edema. Additionally, with the instillation of PGE1 into the perfusate to further inhibit platelet aggregation, no prevention of lung protection by PGE1-treated platelets was seen when these results were compared with those from studies in which lungs were infused with xanthine oxidase and PGE1. Aggregometry studies documented that the inhibitory effect of PGE1 on platelet aggregation persisted for up to 60 minutes, which was the duration of the isolated lung protocol. We conclude that platelet aggregation and release of platelet factors is not required for platelet attenuation of oxidant lung edema.
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PMID:Effects of prostaglandin E1 on platelet attenuation of oxidant-induced edema in isolated rabbit lungs. 224 56

Reactive oxygen species mediate injury and inflammation in many tissues. The addition of xanthine and xanthine oxidase to perfused rat lungs led to increases in peak airway pressure and perfusion pressure, pulmonary edema, and increased protein content in bronchoalveolar lavage fluid. Treatment with 1-10 micrograms.kg-1.min-1 of vasoactive intestinal peptide (VIP), a widely distributed neuropeptide, markedly reduced or totally prevented all signs of injury. Simultaneously, VIP also diminished or abolished the associated generation of arachidonate products. Similar protection was provided by catalase (100 micrograms/ml) but not by the VIP-related peptides secretin or glucagon. The pulmonary vasodilator papaverine (0.15 mg/ml) was also ineffective. Injured lungs that were not treated with VIP released large amounts of this peptide in the perfusate. The results indicate that VIP has potent protective activity against injury triggered by xanthine/xanthine oxidase and may be a physiological modulator of inflammatory tissue damage associated with toxic oxygen metabolites.
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PMID:Vasoactive intestinal peptide prevents lung injury due to xanthine/xanthine oxidase. 238 32

We have developed a model of reperfusion injury in Krebs buffer-perfused rabbit lungs, characterized by pulmonary vasoconstriction, microvascular injury, and marked lung edema formation. During reperfusion there was a threefold increase in lung superoxide anion (O2-) production, as measured by in vivo reduction of nitroblue tetrazolium, and a twofold increase in the release of O2- into lung perfusate, as measured by reduction of succinylated ferricytochrome c. Injury could be prevented by the xanthine oxidase inhibitor allopurinol, the O2- scavenger SOD, the hydrogen peroxide scavenger catalase, the iron chelator deferoxamine, or the thiols dimethylthiourea or N-acetylcysteine. The protective effect of SOD could be abolished by the anion channel blocker 4,4'-diisothiocyano-2,2'-stilbene disulfonic acid, indicating that SOD consumes O2- in the extracellular medium, thereby creating a concentration gradient favorable for rapid diffusion of O2- out of cells. Our results extend information about the mechanisms of reperfusion lung injury that have been assembled by studies in other organs, and offer potential strategies for improved organ preservation, for treatment of reperfusion injury after pulmonary thromboembolectomy, and for explanation and therapy of many complications of pulmonary embolism.
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PMID:Role of reactive oxygen species in reperfusion injury of the rabbit lung. 246 23


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