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)

In addition to the hemodynamic components, the roles of various humoral factors have been emphasized in the progression of vascular and renal injury in hypertension. Radical scavenging properties have attracted much attention in this field. This article discusses the implication of antioxidant properties of the antihypertensive diuretic indapamide on renal injury in Dahl salt-sensitive (Dahl S) rats. Hydroxyl radicals, oxygen radicals toxic to cellular membranes, are eradicated by indapamide in different assay systems, e.g., reduction of alpha-alpha-diphenyl-beta-picrylhydrazyl, rat brain homogenate, or xanthine-xanthine oxidase systems. Such antioxidant effects of indapamide are primarily due to inhibition of lipid peroxidation induced by hydroxyl radicals, and this mechanism may stimulate prostacyclin generation through activation of prostacyclin synthase. In fact, the antioxidant properties of indapamide are well expressed in vivo as well; indapamide treatment reduced oxygen radicals in the kidney of Dahl S rats with hypertension. This was accompanied by a functional improvement of the kidney; decreases in urinary protein and n-acetylglucosaminidase excretion and an increase in glomerular filtration rate were observed. In addition, indapamide morphologically ameliorated the renal injury, and decreased glomerular sclerosis score, arterial injury, and renal tubular injury. Trichloromethiazide reduces blood pressure similar to that produced by indapamide. However, trichloromethiazide did not lead to reduction of oxygen radicals in the kidney, and did not improve the functional disturbance or morphological injury seen in Dahl S rats. These results indicate that indapamide has antioxidant properties, and in addition to blood pressure reduction, such radical scavenging effects may contribute to its beneficial effects on renal function in vivo.
J Cardiovasc Pharmacol 1993
PMID:Oxygen radical scavengers and renal protection by indapamide diuretic in salt-induced hypertension of Dahl strain rats. 750 60

We investigated the effects of the xanthine oxidase (XO)/hypoxanthine (HX) free radical (FR) generating system on the relaxant properties of aortic rings from New Zealand White rabbits. This system generates superoxide anions, hydroxyl radicals, and H2O2. We wished to identify which of these species is responsible for impairment of vascular function. After obtaining dose-response curves to phenylephrine (PE) and carbachol or sodium nitroprusside (SNP), we exposed rings to the FR generating system or H2O2 for 30 min, either with or without a range of potentially protective agents. Dose-response curves to carbachol or SNP were then repeated. Exposure to the XO/HX system impaired endothelium-dependent, carbachol-induced relaxation. The hydroxyl radical scavengers mannitol, N-(2-mercaptopropionyl)-glycine (MPG), and captopril offered no protection. Superoxide dismutase (SOD) increased the impairment of response, catalase provided partial protection, and a combination of SOD and catalase completely prevented impairment of the response. H2O2 mimicked the effects of XO/HX system. H2O2 appears to be the primary species involved in mediating the toxic effects of the XO/HX FR generating system, but the superoxide anion is probably responsible for some of the loss of relaxation and a role for intracellular generation of hydroxyl radicals cannot be excluded.
J Cardiovasc Pharmacol 1993 Dec
PMID:Effects of a xanthine oxidase/hypoxanthine free radical and reactive oxygen species generating system on endothelial function in New Zealand white rabbit aortic rings. 750 95

"Declamping shock" is observed after aortic crossclamping, with hypovolemia, hypotension, and metabolic acidemia invariably present. We hypothesized that oxidants derived from xanthine oxidase influence the resuscitative interventions required to maintain baseline hemodynamic and acid-base status after aortic occlusion and reperfusion in rabbits. We also hypothesized that inactivation of xanthine oxidase with sodium tungstate could reduce systemic injury as assessed by the release of lactate dehydrogenase and alkaline phosphatase. To test these hypotheses, we established aortic occlusion in rabbits (n = 10, standard diet; n = 8, tungstate diet) for 40 minutes by inflation of a 4F Fogarty catheter in the descending thoracic aorta followed by 2 hours of reperfusion. Sham-operated rabbits (n = 10, standard diet; n = 9, tungstate diet) served as controls. Tungstate-pretreated rabbits required significantly less Ringer's solution (28%), phenylephrine (68%), and sodium bicarbonate (30%) during reperfusion (p < 0.005). Lactate dehydrogenase and alkaline phosphatase release during reperfusion was significantly attenuated by tungstate pretreatment (p < 0.05). Tungstate pretreatment resulted in plasma xanthine oxidase activities significantly lower than those in the sham group administered a standard diet (p = 0.007). Resuscitation requirements and systemic injury were reduced by inactivation of xanthine oxidase in a rabbit model that simulates the situation of human thoracic aorta operations.
J Thorac Cardiovasc Surg 1995 Sep
PMID:Xanthine oxidase inactivation attenuates postocclusion shock after descending thoracic aorta occlusion and reperfusion in rabbits. 756 38

Allopurinol reduces formation of cytotoxic free radicals during myocardial ischemia/reperfusion in animals. To evaluate the effect of allopurinol on cardiac performance and metabolism after coronary bypass in humans, we divided 33 patients into two groups: 15 patients (controls) received no allopurinol and 18 patients received 200 mg allopurinol intravenously (i.v.) 1 h preoperatively. Hemodynamic measurements were made with a triple-lumen thermodilution pulmonary artery catheter before cardiopulmonary bypass (CPB), 30 min after completion of CPB and 6 h later in the intensive care unit (ICU). A catheter placed into the coronary sinus was used for blood sampling for measurement of lactate and creatine phosphokinase MB. Peripheral blood was obtained for measurement of xanthine oxidase activity (XO), uric acid, and thiol groups. A myocardial biopsy was taken for measurement of thiol group content and XO before CPB and after heparin neutralization with protamin (a few minutes after CPB). Treated patients had better recovery of cardiac output (CO) and left ventricular stroke work (LVSW) 30 min and 6 h after completion of CPB than did controls. Allopurinol significantly reduced plasma XO. Plasma concentrations of uric acid increased significantly in both groups 30 min after completion of CPB, but the increase in controls was greater (p < 0.02) than with allopurinol. Thiol group levels increased (p < 0.05) only in controls. Our results demonstrate improvement of cardiac function in coronary artery bypass surgery with allopurinol that is related to its metabolic effects consistent with protection against XO catalyzed free radical-mediated injury.
J Cardiovasc Pharmacol 1995 Jan
PMID:Improvement of cardiac function by allopurinol in patients undergoing cardiac surgery. 772 40

Production/release of superoxide anions from aortic rings was measured by a modified lucigenin-enhanced chemiluminescence (CL) technique. The aortic rings were obtained from control and cholesterol-fed (1% for 12 weeks) rabbits. The CL signal was significantly increased in aortic wall of cholesterol-fed rabbits. Pretreatment with oxypurinol, an inhibitor of xanthine oxidase, had a slight but insignificant effect on the CL response produced by aortic rings from control animals but significantly reduced CL response to aortic rings from cholesterol-fed rabbits. Pretreatment with diethyldithiocarbamate (DETC), an inhibitor of intrinsic superoxide dismutase (SOD), increased the CL signal for both animal groups, but this increase was greatly aggravated in aortic rings from hypercholesterolemic rabbits. Addition of phorbol 12-myristate 13 acetate (PMA) to stimulate the respiratory burst of wall-adherent and/or resident leukocytes had only slight effect on the CL response to aortic rings from control animals but extensively stimulated photon emission of aortic rings from cholesterol-fed rabbits. These findings are in agreement with the concept that the arterial wall in hypercholesterolemia and/or atherosclerosis is under increased "oxidative stress."
J Cardiovasc Pharmacol 1994 Dec
PMID:Vascular release of superoxide radicals is enhanced in hypercholesterolemic rabbits. 789 85

Oxygen free radicals mediate the ischemia-reperfusion damage in animal hearts, but their role in human beings is still controversial because of the low xanthine oxidase level in the human heart. Besides ischemia-reperfusion, cardiac operation also includes other major interventions that might generate free radicals but have not been systematically studied. We studied the cases of nine patients throughout coronary artery operations, including general anesthesia, heparin, protamine and administration of cardioplegic solution, extracorporeal circulation, and heart reperfusion. Arterial plasma was assayed for malondialdehyde, diene conjugates, and fluorescent chromolipids, and plasma antioxidant activity was estimated from the ability to trap peroxyl radicals. Anesthesia, surgical procedures, or heparin administration did not change these parameters. Extracorporeal circulation decreased the plasma concentration of diene conjugates immediately, whereas other compounds remained unaltered. When these concentrations were corrected for hemodilution, the amount of fluorescent chromolipids actually increased after 5 minutes of extracorporeal circulation to 177% +/- 14% (mean +/- standard error of the mean), diene conjugates increased to 138% +/- 12%, and plasma antioxidant capacity increased to 144% +/- 12% of the awake value. Fluorescent chromolipid values remained at 156% to 177% throughout the perfusion and decreased to 130% +/- 13% 1 hour after perfusion. Diene conjugate levels and antioxidant capacity were 123% to 144% and 143% to 161%, respectively, from baseline during perfusion and 119% +/- 5% and 135% +/- 9%, respectively, 1 hour after perfusion. Heart reperfusion or protamine administration showed no additional increases. Malondialdehyde concentrations varied and showed no statistically significant alterations. We conclude that extracorporeal circulation devices induce generation of free radicals and plasma antioxidant activity, which are different from the damage caused by ischemia-reperfusion.
J Thorac Cardiovasc Surg 1994 Jul
PMID:Free radical reaction products and antioxidant capacity in arterial plasma during coronary artery bypass grafting. 802 57

In this prospective, randomized, double-blind, placebo-controlled study, the clinical, biochemical, and hemodynamic effects of xanthine oxidase inhibition in patients undergoing coronary artery bypass grafting were assessed. Allopurinol pretreatment significantly reduced the use of inotropic support after the operation (5 of 25 patients versus 13 of 25 patients, p < 0.01) and increased the rate of peripheral warming (11.4 +/- 0.85 hours versus 14.4 +/- 1 hours, p < 0.02). Twenty patients (9 in the allopurinol group and 11 in the placebo group) underwent invasive hemodynamic monitoring and intraoperative coronary sinus cannulation. The cardiac indexes of both groups were similar before the operation and for the first postoperative hour; thereafter, the cardiac index increased significantly in only the active treatment group (F = 3.33 and df = 5.90, p < 0.004). Products of lipid peroxidation (thiobarbituric acid reactive substances) increased significantly in only the placebo group, with increases being evident both in the systemic circulation (9.5 +/- 3.2 nmol/gm albumin, p < 0.007, and 24 +/- 5 nmol/gm albumin, p < 0.001, at 30 seconds and 2 minutes of reperfusion, respectively) and the coronary sinus (19.4 +/- 5.8 nmol/gm albumin, p < 0.004, and 28 +/- 4 nmol/gm albumin, p < 0.001, at 2 and 5 minutes of reperfusion, respectively. No significant difference was evident between the groups with respect to cardiac enzyme or vitamin E release. It is proposed that xanthine oxidase inhibition exerts its beneficial effects by reducing the level of free radical activity associated with reperfusion during coronary artery bypass grafting.
J Thorac Cardiovasc Surg 1994 Jan
PMID:Allopurinol pretreatment improves postoperative recovery and reduces lipid peroxidation in patients undergoing coronary artery bypass grafting. 828 93

Purine efflux from transplanted human cardiac allografts was investigated as a potential biochemical correlate to graft preservation and eventual function. Coronary sinus effluent from 14 allografts was sampled at 1, 5, 10, 15, 20, and 25 minutes after reperfusion. The plasma fraction from each sample was analyzed for hypoxanthine, xanthine, urate, inosine, and adenosine by high-performance liquid chromatography. Total organ preservation time, aortic crossclamp and bypass times, and initial cardiac index off bypass were recorded. An inotropic score was calculated from the dosages of inotropic agents each recipient required immediately after transplantation. Inosine and adenosine were not detectable in the coronary sinus effluent at any time during reperfusion. Hypoxanthine concentration rose sevenfold (p < 0.001) 1 minute after reperfusion. Xanthine concentration peaked later at 5 minutes after reperfusion, a twofold increase (p < 0.02). As reperfusion continued, hypoxanthine and xanthine concentrations returned toward baseline levels. The rise in coronary sinus xanthine concentration provides evidence for hypoxanthine degradation by xanthine oxidase during the immediate reperfusion period. The extent of hypoxanthine efflux correlated with total graft ischemic time (p < 0.05), inotropic score (p < 0.005), and the time from crossclamp release to cessation of bypass (p < 0.01). Hypoxanthine efflux can be used as a sensitive and objective biochemical indicator of graft preservation and immediate function.
J Thorac Cardiovasc Surg 1994 Feb
PMID:Purine efflux from transplanted human cardiac allografts. Correlation with graft function. 830 67

Reperfusion after global cardiac ischemia may injure coronary artery endothelium and lead to vasospasm and thrombosis. Oxygen-derived radicals have been implicated as mediators of this process, but the precise mechanism of injury is unknown. We hypothesized that oxygen-derived radicals impair coronary endothelial production of nitric oxide, a potent endogenous vasodilator and inhibitor of platelet adhesion. To test this theory, we developed an in vitro model of reperfusion injury in which segments of epicardial canine coronary artery were suspended in organ chambers (physiologic salt solution, 37 degrees C, 95% oxygen and 5% carbon dioxide) and exposed to oxygen-derived radicals (generated by adding xanthine [10(-4) mol/L] and xanthine oxidase [100 mU/ml] to the bathing solution for 70 minutes). After exposure to oxygen-derived radicals, epicardial coronary artery smooth muscle exhibited normal contraction to potassium ions (20 mmol/L) and prostaglandin F2 (4 x 10(-6) mol/L); also, the rings relaxed normally on exposure to isoproterenol and sodium nitroprusside (10(-9) to 10(-4) mol/L) (n = 6). In contrast, endothelium-dependent vasodilatation to receptor-dependent agonists acetylcholine and adenosine diphosphate (10(-9) to 10(-4) mol/L) was impaired as compared with the reaction of control vessels not exposed to oxygen-derived radicals (n = 18, P < 0.001, and n = 10, P < 0.002, respectively). Importantly, receptor-independent, endothelium-dependent relaxation to the calcium ionophore A23187 was normal (n = 6). Further, endothelium-dependent vasodilatation to receptor-dependent agonist bradykinin (non-nitric oxide pathway) was normal after exposure to oxygen-derived radicals. This is the first study to demonstrate that oxygen-derived radicals selectively impair receptor-dependent nitric oxide production by the coronary endothelium. Diminished nitric oxide production is a likely mechanism of vasospasm and thrombosis after reperfusion of the ischemic heart.
J Thorac Cardiovasc Surg 1994 Feb
PMID:Oxygen radical-mediated vascular injury selectively inhibits receptor-dependent release of nitric oxide from canine coronary arteries. 830 70

The release of xanthine oxidase/dehydrogenase XO/XDH (4.99 +/- 1.08 x 10(-12) moles/min/g wet wt in aerobic hearts) was not significantly increased following 30 min of ischemia, but almost doubled following 45 min of ischemia, indicating some endothelial cell damage. This release, however, was small compared to the release induced by digitonin perfusion (26 fold increase in an equivalent volume of effluent) and was nearly 1000 fold less than the enzyme activity measured in the tissue homogenate. There was a significant decrease in cardiac function (heart rate and systolic pressure) following 30 min of ischemia and no recovery of function following 45 min of ischemia and reperfusion. Endothelial cell damage determined by XO/XDH release is negligible during times of ischemia that cause severe damage to myocardial contractility. Coronary endothelial cells should not contribute significantly to circulating XO/XDH levels following ischemia.
Am J Cardiovasc Pathol 1993
PMID:Xanthine oxidase/dehydrogenase release following ischemia in isolated rat hearts. 830 95


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