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

Anisodamine, a Chinese traditional medicine herb, has been used for treatment of adult respiratory distress syndrome effectively, but little is known about its mechanism. We attempted to investigate if anisodamine could protect bovine pulmonary endothelial cell injury induced by exogenous oxygen-free radicals that were generated by xanthine/xanthine oxidase or opsonized zymosan-stimulated polymorphonuclear leukocytes. Results showed that with the addition of xanthine/xanthine oxidase into cultured bovine pulmonary endothelial cells, production of malondialdehyde and release of lactate dehydrogenase in supernatant increased, and synthesis of prostacyclin decreased. Damaged cellular membranes were revealed by scanning electron microscopy. The same was true for the addition of opsonized zymosan-stimulated polymorphonuclear leukocytes. While treatment with anisodamine greatly attenuated all of the above-mentioned parameters, results showed that (1) cultured bovine pulmonary endothelial cells could be damaged by oxygen-free radicals, (2) anisodamine had a protective effect on this injury as effective as that of superoxide dismutase and catalase, and (3) the membrane-stable action might contribute to the mechanism of protective effect against this injury.
 ...
PMID:Protective effect of anisodamine on cultured bovine pulmonary endothelial cell injury induced by oxygen-free radicals. 141 86

Conflicting data have been reported on the relationship between reactive oxygen intermediates and the formation of oxygenase-derived eicosanoids. Plasma levels of prostacyclin (PGI2, measured as the stable metabolite 6-keto-PGF1 alpha) and thromboxane A2 (TxA2, measured as TxB2) in the effluent blood of a canine ileal segment were determined following 1 or 2 h of ischemia. The synthesis of both eicosanoids was significantly stimulated during reperfusion, but extension of the ischemic interval from 60 to 120 min was not followed by a further increase. The role of oxidants potentially involved in the process was investigated by using materials that inactivate the xanthine-oxidase-generated intermediates. Previous studies on the same in vivo animal model had demonstrated the effectiveness of antioxidant therapy in reducing the postischemic histamine release. There was no significant alteration in the amount of eicosanoids synthesized following oral allopurinol, catalase, dimethylsulfoxide, mannitol or desferrioxamine treatment. Intravenously administered allopurinol, however, significantly elevated the postischemic 6-keto-PGF1 alpha/TxB2 ratio. The results suggest that these antioxidants at doses inhibitory to histamine liberation are not effective in influencing the postischemic eicosanoid release. Intravenously administered allopurinol could exert a potentially beneficial effect through a mechanism other than the blockade of xanthine oxidase.
 ...
PMID:Effect of antioxidant therapy on cyclooxygenase-derived eicosanoid release during intestinal ischemia-reperfusion. 178 59

The effects of human neutrophil elastase (HNE), cathepsin-G, H2O2, xanthine oxidase-hypoxanthine derived superoxide anion and endotoxin on the PGI2 production by cultured bovine pulmonary endothelial cells were observed. The results showed that HNE, superoxide anion and H2O2 could decrease the PGI2 production by endothelial cells, and cathepsin-G had no effect on the production of PGI2. In our experiment, endotoxin could enhance PGI2 production. It was suggested that HNE, superoxide anion, and H2O2 may be involved in the pathogenesis of pulmonary hypertension.
 ...
PMID:[Effect of human neutrophil elastase, cathepsin--G. superoxide anion and endotoxin on the PGI2 production by cultured bovine pulmonary endothelial cells]. 180 32

This study was directed to the ability of oxygen free radicals to cause reversible vascular endothelial cell dysfunction. A well-characterized system for the production of the superoxide anion radical (O2(-).) and hydrogen peroxide (H2O2), employing xanthine and xanthine oxidase, was used to sublethally injure human umbilical vein endothelial (HUVE) cells in vitro. We examined the effects of a 15-minute incubation of HUVE cells with xanthine (50 microM) and xanthine oxidase (2.5-100 munits) on platelet adherence and prostacyclin (PGI2) release. All experiments were conducted in a serum-free N-(2-hydroxyethyl)piperazine-N'-(2-ethanesulfonic acid)-Tyrode buffer (pH 7.4) incubation system. Exposure of HUVE cells to sublethal concentrations of oxygen free radicals caused significant enhancement of platelet adherence (65 +/- 6.3%) to injured endothelium. A 12-fold increase in PGI2 release resulted after a 15-minute treatment with xanthine and xanthine oxidase. The addition of exogenous PGI2 (150 mM) to platelet-endothelial systems did not completely prevent the enhanced platelet adherence, suggesting that a lack of PGI2 was not completely responsible for the adherence of platelets to O2(-).-injured cells. When superoxide dismutase (SOD) and catalase, scavengers of O2(-). and H2O2, were added in combination to treated cells, platelet adherence decreased by 42-77% and PGI2 release approached that of control cultures. No decrease in either platelet adherence or PGI2 release occurred when chemically inactivated forms of SOD and catalase or bovine serum albumin were added to oxidant-treated cultures.
 ...
PMID:Alterations in human vascular endothelial cell function by oxygen free radicals. Platelet adherence and prostacyclin release. 185 31

Using organ perfusing methods, the effect of activated neutrophils on pulmonary arterial pressure was examined. Lung of the rats were perfused with warm (37 degrees C) Krebs solution in constant flow rate. Perfusing pressure was obviously increased when adding activated PMN to the perfusate and permeability of pulmonary capillaries increased too. Elastase and oxygen free radical (OFR) were released by activated PMN. Human neutrophil elastase (HNE) and oxygen free radical produced from the reaction between xanthine and xanthine oxidase could inhibit PGI2 production by cultured bovine pulmonary arterial endothelial cells. OFR increased the tension of rabbit pulmonary arterial ring, and this effect was independent on endothelial cells. Results suggested that activated neutrophils and products released by them could directly cause the constriction of pulmonary arterial smooth muscle or inhibit PGI2 production which would increase the tension of pulmonary vessels. All this may play role in pathogenesis of pulmonary hypertension.
 ...
PMID:[Effect of products released by activated neutrophils on pulmonary arterial pressure]. 208 53

Indapamide, a nonthiazide diuretic, exhibits direct vasodilator action as well as natriuretic and diuretic effects. Although calcium antagonist-like activity has been addressed so far, the mechanisms for vasodilator effect are still uncertain. To understand the wide range of indapamide actions, we examined the effects of indapamide on the vascular eicosanoid generation and investigated its mechanisms by using rat vascular smooth muscle cells in culture. Indapamide uniquely increased the prostacyclin generation in the vascular smooth muscle cells in a dose-dependent manner, whereas it did not affect the vasoconstrictor thromboxane A2. Thiazide diuretics lowered the prostacyclin generation, while nonthiazide derivatives did not affect the biosynthesis. Enzymatic analysis revealed that indapamide affected neither [14C]arachidonate liberation nor prostacyclin synthase of the smooth muscle cells. Indapamide eliminated a stable free radical in a cell-free system, lowered the formation of malondialdehyde from lipid peroxides in rat brain homogenate, and reduced lipid peroxidation by the free radical generating system of xanthine-xanthine oxidase. Indeed, the scavenging action of indapamide significantly attenuated the inhibitory activity of 15-hydroperoxy-arachidonate to prostacyclin synthase activity. These results indicate that indapamide diuretic increases prostacyclin generation in the vascular smooth muscle cells possibly through antioxidant effects and that the enhanced prostacyclin generation is partly responsible for its direct vasodilator action.
 ...
PMID:Radical scavengers of indapamide in prostacyclin synthesis in rat smooth muscle cell. 210 10

Using a left lung orthotopic isograft model in AS strain rats, we have investigated ultrastructural changes in lungs preserved for 48 h at 0 degrees C after a simple flush technique. Lungs were examined after storage alone and after storage followed by up to 1 h reperfusion with blood in vivo. Grafts were flushed with either isotonic saline (NaCl) or hypertonic citrate solution (HCA) alone, or with HCA containing either verapamil (a Ca2+ channel blocker), desferrioxamine (a Fe2+ antagonist), prostacyclin PGI2, nifedipine (a Ca2+ channel blocker) or allopurinol (a xanthine oxidase inhibitor). These agents were also given intravenously to both donor and recipient. Storage in NaCl produced gross cytoplasmic swelling and disruption with widespread nuclear injury. Reperfusion for 1 h resolved cell swelling but some endothelial loss and alveolar capillary wall rupture were seen. HCA with or without additional agents protected against cell swelling but endothelial blebbing and widening of the basement membrane occurred. Reperfusion for 1 h led to recovery of the basement membrane thickness but widespread endothelial loss was observed which was reduced by the addition of verapamil, desferrioxamine, nifedipine or allopurinol to the flush, but not by prostacyclin. Examination of lungs reperfused for shorter periods (5 and 15 min) identified three main types of damage to the vascular endothelium: (1) gross cell swelling, (2) detachment of intact endothelial cells from the underlying basal lamina, and (3) attenuation of cytoplasm due to blebbing. The results suggest that endothelial injury occurring on reperfusion is partly Fe2+ and Ca2(+)-mediated and that reactions catalysed by xanthine oxidase (which include oxygen free radical production) may also be important.
 ...
PMID:Ultrastructural changes in rat lungs after 48 h cold storage with and without reperfusion. 211 17

Endothelium-dependent contractions to acetylcholine and endothelium-independent contractions to oxygen-derived free radicals in the aorta of the spontaneously hypertensive rat (SHR) are mediated by an unidentified product of the cyclooxygenase pathway of arachidonic acid metabolism. To determine the role of thromboxane A2 (TXA2) or prostaglandin H2 (PGH2) in these contractions, rings of the thoracic aorta of SHR were suspended in organ chambers for measurement of isometric force. Acetylcholine caused endothelium-dependent contractions in quiescent rings from SHR aortas. Oxygen-derived free radicals generated with xanthine plus xanthine oxidase caused contractions in rings without endothelium. Dazoxiben (thromboxane synthetase inhibitor) did not affect contractions evoked by acetylcholine. AH 23,848, SQ 29,548, or R 68,070 (TXA2/PGH2 receptor antagonists) inhibited contractions to U 46,619 (a TXA2/PGH2 receptor agonist), acetylcholine, and oxygen-derived free radicals. Acetylcholine stimulated the release of prostacyclin from Wistar-Kyoto (WKY) rat and SHR aortas but not the release of other prostaglandins (PGE2, PGF2 alpha, TXA2). Oxygen-derived free radicals did not stimulate the release of prostaglandins from either SHR or WKY rat aortas. These results demonstrate that stimulation of TXA2/PGH2 receptors probably by PGH2 might be involved in endothelium-dependent contractions. Oxygen-derived free radicals, which might be an endothelium-derived contracting factor or factors, ultimately cause contraction by stimulation of TXA2/PGH2 receptors.
 ...
PMID:Thromboxane A2 receptor antagonists inhibit endothelium-dependent contractions. 214 Oct 3

Endothelium regulates smooth muscle tone in response to various agonists and antagonists by release of vasorelaxing and vasoconstricting factors. It also has been postulated that superoxide radicals, which degrade endothelium-derived relaxing factor, exert smooth muscle-constrictor effects. To determine the role of superoxide radicals on vasomotor tone, we exposed rat thoracic aortic rings in vitro to a superoxide radical-generating system of xanthine and xanthine oxidase (X + XO). In rings with intact endothelium, X + XO caused modest smooth muscle contraction and increased vascular sensitivity to both l-epinephrine and thromboxane A2 (TxA2) "mimic" U46619. These vascular contractile effects were more pronounced in rings without intact endothelium. In the supernates of vascular rings with intact endothelium, TxA2 and prostacyclin metabolites were identified on exposure of vascular rings to X + XO, indicating stimulation of the cyclooxygenase pathway. Although both superoxide radical scavenger superoxide dismutase and cyclooxygenase inhibitor indomethacin blocked release of TxA2 and prostacyclin, only superoxide dismutase blocked the contractile effects of superoxide radicals (p less than 0.05). Neither catalase nor mannitol had any effect on X + XO mediated vasoconstriction, suggesting that hydrogen peroxide and hydroxyl radicals did not participate in the observed effects of X + XO. Exposure of vascular rings to X + XO revealed extensive endothelial disruption as determined by scanning electron microscopy. Thus superoxide radicals exert procontractile effects on vascular smooth muscle and enhance its response to l-epinephrine and TxA2 mimic. These effects are probably exerted by injury to the endothelial barrier.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Superoxide radical-mediated endothelial injury and vasoconstriction of rat thoracic aortic rings. 216 May 8

Defibrotide is known to enhance prostacyclin (PGI2) release from the vascular endothelium. We investigated the vasoactive effects of defibrotide in isolated rat hearts perfused at constant flow subjected to ischaemia and reperfusion. Defibrotide at 10 or 100 micrograms/ml did not exert any direct vasoactive effect on normal rats hearts. However, ischaemia and reperfusion resulted in an impaired vasodilation to acetylcholine, an endothelium-dependent vasodilator. In contrast, the vasodilator response to the endothelium-independent dilator, nitroglycerin, was unaffected. Defibrotide, at 10 or 100 micrograms/ml, markedly restored the vasodilation to acetylcholine 10 nmol/l to 1 mumol/l (P less than 0.01) without influencing the vasodilator response to nitroglycerin (2 to 200 micrograms/l). Haemoglobin (150 nmol/l) inhibited the dilation to acetylcholine in response to defibrotide. However, no evidence of PGI2 release was observed with acetylcholine-induced vasodilation in the presence or absence of defibrotide. Additionally, 10-100 micrograms/ml of defibrotide did not significantly decrease superoxide radicals generated by a xanthine-xanthine oxidase synthetic system under conditions in which superoxide dismutase was effective. Thus, defibrotide appears to exert an endothelium-protective effect preserving endothelium-derived relaxing factor (EDRF) without directly scavenging free signals.
 ...
PMID:Coronary endothelium-protective effects of defibrotide in ischaemia and reperfusion. 216 Jun 17


1 2 3 4 5 Next >>