Disease relevance of Alloxanthine

• Superoxide dismutase and oxypurinol decreased lucigenin chemiluminescence in ulcerative colitis by -63% (P less than 0.05) and -27% (P less than 0.05), respectively [1].
• Allergic reaction to allopurinol with cross-reactivity to oxypurinol [2].
• Myocardial infarct size (percent of risk region) was less in oxypurinol-treated dogs, 32 +/- 16%, compared with that of the control group, 46 +/- 15% [3].
• Oxypurinol limits myocardial stunning but does not reduce infarct size after reperfusion [4].
• Long-term use of 300 mg per day of allopurinol was found to result in elevated steady-state serum oxipurinol concentrations in patients with renal insufficiency (serum oxipurinol concentration in micromoles per liter = -2.5 X creatinine clearance in milliliters per minute + 326) [5].

Psychiatry related information on Alloxanthine

• Oxypurinol (40 mg/kg, IP), administered 20 min prior to carotid occlusion, prevented the increase in locomotor activity observed in saline-injected ischemic animals and significantly reduced the damage to, and loss of, CA1 hippocampal neurons observed 5 days postischemia [6].

High impact information on Alloxanthine

• We conclude that with the low-protein diet, the absorption, metabolism, and excretion of allopurinol were minimally altered but the total-body clearance of oxypurinol was greatly reduced because of a large increase in the net renal tubular reabsorption of oxypurinol [7].
• Urinary-tract stones resulting from the excretion of oxypurinol [8].
• Pretreatment with 0.5 mM oxypurinol attenuated the synergistic effect of TNF alpha and H2O2 on endothelial permeability [9].
• When the patient's lymphocytes were exposed in vitro to oxypurinol and allopurinol, increased DNA synthesis was observed, suggesting an immunologic basis for the reaction [2].
• To explore the role of oxygen free radicals produced by the xanthine oxidase pathway on infarct size and left ventricular function, the effect of oxypurinol, an active metabolite of allopurinol and a potent noncompetitive inhibitor of xanthine oxidase, was assessed in a 90 min, closed-chest, canine preparation of occlusion-reperfusion [4].

Chemical compound and disease context of Alloxanthine

• Combined treatment with oxypurinol and pentoxifylline almost completely abolished ascites, MAPK phosphorylation in the pancreas, and the increase in lung myeloperoxidase activity [10].
• Twenty patients (19 males, 66+/-8 years) with stable coronary disease, severely suppressed systolic function (left ventricular ejection fraction 22+/-2%), and nonelevated uric acid plasma levels received a single intravenous dose of oxypurinol (400 mg) [11].
• Adenosine levels were lower in oxypurinol-treated rats, during ischemia, and in the initial reperfusion phase [12].
• Using specific inhibitors of NAD(P)H oxidase and XO, gp91ds-tat and oxypurinol, respectively, we show that the constitutively active NAD(P)H oxidase was blocked following hypoxia while XO was activated [13].
• Urate crystalluria was controlled by allopurinol therapy but renal calculi developed, which contained a variety of purines, particularly the relatively insoluble xanthine, as well as oxypurinol and hypoxanthine [14].

Biological context of Alloxanthine

• However, oxypurinol-treated animals demonstrated an improved regional ventricular function at 3 hr after reperfusion (0.7 +/- 2.6% vs -2.8 +/- 2.0%) and a significant improvement at 24 hr (5.4 +/- 2.5% vs -3.2 +/- 1.7%; p less than .05) [4].
• Thus, the inhibition kinetics of oxypurinol for XO was determined using saturating concentrations of xanthine [15].
• RESULTS: Oxypurinol prevented p38 phosphorylation in the pancreas and partially avoided the rise in lung myeloperoxidase activity [10].
• Physiological indices, namely, time to recovery of mean arterial blood pressure and time to onset of respiration, were also shortened in the oxypurinol-treated animals [12].
• These results show that pretreatment with oxypurinol protects acutely ischaemic myocardium, producing enhanced myocardial blood flow, diminished systolic bulge during occlusion, and markedly enhanced function recovery following reperfusion [16].

Anatomical context of Alloxanthine

• Similar to the results obtained with HS6B-XO, the binding of XO to bovine aortic endothelial cells rendered the enzyme resistant to inhibition by oxypurinol, achieving approximately 50% inhibition [15].
• Superoxide dismutase and/or catalase, or oxypurinol added to cultures before hypoxia efficiently prevented neutrophil adhesion [17].
• Treatment with either oxypurinol or superoxide dismutase largely prevented the leukocyte recruitment, platelet-leukocyte aggregation, mast cell degranulation, and enhanced DHR oxidation elicited by I/R in HCh rats [18].
• Oxypurinol improves coronary and peripheral endothelial function in patients with coronary artery disease [19].
• Flow-mediated dilation of the brachial artery, assessed in eight consecutive patients, increased from 5.1+/-1.5 before to 7.6+/-1.5% after oxypurinol administration (p < 0.05) [19].

Associations of Alloxanthine with other chemical compounds

• The XO reducing substrates xanthine, NADH, and 2,3-dihydroxybenz-aldehyde triggered nitrite reduction to NO, and the molybdenum-binding XO inhibitor oxypurinol inhibited this NO formation, indicating that nitrite reduction occurs at the molybdenum site [20].
• In agreement with this concept, the enzymatic reduction of CysNO by XO was inhibitable by oxypurinol and diphenyliodonium, inhibitors that interfere with the catalytic cycle at the molybdenum and flavin sites, respectively [21].
• Male Sprague-Dawley rats were subjected to 35 min of bilateral renal arterial occlusion with or without oxypurinol/benzoate therapy [22].
• We conclude that the decreased CLR of oxypurinol was the result of the reduced protein content of the diet and the CLR of both inulin and creatinine were decreased on the low-protein diet [23].
• Inhibition of O2- with superoxide dismutase, oxypurinol, tiron, or the superoxide dismutase mimetic Mn(III)tetrakis(4-benzoic acid)porphyrin chloride did not restore but further deteriorated the relaxation of LPS-treated rings [24].

Gene context of Alloxanthine

• Notably, cytotoxicity by M239V-PS2 could be inhibited by the combination of two clinically usable inhibitors of superoxide-generating enzymes, apocynin and oxypurinol [25].
• The uptake of oxypurinol by another organic anion transporter (OAT), OAT4 (SLC22A11), which is also expressed at the apical membrane of proximal tubular epithelial cells, was negligible, whereas the uptake of [3H]estrone-3-sulfate by OAT4 was significantly inhibited by oxypurinol [26].
• The NAT2 phenotype did not influence CYP1A2 and XO ratios or plasma oxypurinol pharmacokinetics [27].
• Uptake of oxypurinol by Xenopus oocytes injected with complementary RNA of URAT1 was significantly higher than that by water-injected oocytes, and the uptake was saturable, with a K(m) of about 800 microM [26].
• Allopurinol and oxypurinol, but not superoxide dismutase or catalase, protected the gastric mucosa 24 h after endothelin-1 injection [28].

Analytical, diagnostic and therapeutic context of Alloxanthine

• Allopurinol and its active metabolite oxypurinol showed considerable promise in the treatment of these conditions both in experimental animals and in small-scale human clinical trials [29].
• Oxypurinol failed to reduce infarct size 24 hr after reperfusion when expressed as a percentage of the area at risk (36.3 +/- 4.9% vs 36.0 +/- 5.6%; p = NS) [4].
• The first fraction was found to contain the fully active form (double-active dimers) from the analyses of spectral changes on addition of xanthine, oxipurinol titration, and ESR slow signal, whereas the second fraction was assumed to contain mixed dimers and double-inactive dimers [30].
• Serum concentrations of both allopurinol and oxipurinol reach levels above 1 X 10(-5) M within minutes of intravenous administration and within 1 or 2 hr of oral administration of 300 mg allopurinol [31].
• Allopurinol and oxypurinol concentrations were determined by high-performance liquid chromatography in aqueous humor and retinal tissue of both control eyes and eyes with uveitis [32].

References