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)

Oxygen free radicals (OFR) exert direct effects on the electrophysiologic properties of a variety of cardiac preparations under well-oxygenated conditions and have been implicated in the genesis of arrhythmias associated with myocardial ischemia and reperfusion. In the present study, we examined the effects of the OFR generating system, purine and xanthine oxidase, on the intracellular electrical activity of canine Purkinje fibers and papillary muscles. Purine and xanthine oxidase generated a concentration-dependent production of superoxide anion. This was accompanied by a time- and concentration-dependent depolarization of the membrane potential and shortening of the action potential duration (APD50 and APD90) in Purkinje fibers. There was no significant effect of any concentration of purine/xanthine oxidase tested on these parameters in the papillary muscles. In addition, we observed a frequency-dependent change in the sensitivity of Purkinje fibers exposed to purine/xanthine oxidase both with respect to the concentration- and time-dependent effects on APD. In the presence of 5.75 mM purine and 25 U/L xanthine oxidase, APD was significantly shortened after 10 min when the Purkinje fiber was stimulated at a basic cycle length (BCL) of 300 ms. At a BCL of 500 ms, APD did not shorten significantly until 40 min. At longer BCL (greater than 800 ms), prolonged periods of exposure were required before any significant change in APD was observed. These results suggest that OFR can alter the electrophysiologic characteristics of cardiac tissues directly and that these effects could potentially exert a proarrhythmic effect, particularly under conditions in which heart rate (HR) is elevated.
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PMID:Differential effects of purine/xanthine oxidase on the electrophysiologic characteristics of ventricular tissues. 169 66

9-(beta-D-1,3-Dioxolan-4-yl)guanine (DXG) exhibits potent antiviral activity against human immunodeficiency virus type 1 (HIV-1) and hepatitis B virus (HBV) in vitro. However, since DXG possesses limited aqueous solubility, a more water soluble prodrug of DXG, 9-(beta-D-1,3-dioxolan-4-yl)-2-aminopurine (APD), was synthesized. The purpose of this study was to characterize the pharmacokinetics of APD and its antiviral metabolite DXG in mice. Female NIH-Swiss mice were administered 100 mg/kg APD intravenously or orally. Serum, brain and liver were collected at selected times following prodrug administration and concentrations of APD and DXG were determined by HPLC. APD was efficiently converted to parent nucleoside DXG following both intravenous and oral administration. Biotransformation of APD to DXG likely occurs in the liver and is mediated by xanthine oxidase. Similar pharmacokinetic profiles for DXG were observed following either route of administration in serum, liver and brain. These results demonstrate that APD appears to be a promising prodrug for the delivery of DXG.
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PMID:Biotransformation and pharmacokinetics of prodrug 9-(beta-D-1,3-dioxolan-4-yl)-2-aminopurine and its antiviral metabolite 9-(beta-D-1,3-dioxolan-4-yl)guanine in mice. 929 58

During myocardial ischemia and the subsequent reperfusion, free radicals are important intermediates of the cellular damage and rhythm disturbances. We examined the effects of superoxide radicals or hydrogen peroxide (H(2)O(2)) on the action potentials in isolated rabbit Purkinje fibers, atrial muscle and ventricular muscle. Reactive oxygen species (ROS) donors such as adriamycin, xanthine/xanthine oxidase and menadione induced prolongation of APD(90) in Purkinje fibers. Menadione (30 microM), the most specific superoxide radical donor, prolonged the action potential duration at 90% repolarization (APD(90)) by 17% in Purkinje fibers, whereas it shortened the APD by 57% in ventricular muscle, and it did not affect the atrial APD. All these menadione-induced effects were completely blocked by 2,2,6,6-tetramethyl- 1-peperadinyloxy, a superoxide radical scavenger. Superoxide dismutase (SOD) activity was lowest in Purkinje fibers, it was moderate in atrial muscle and highest in ventricular muscle. H(2)O(2) shortened the APDs of all three cardiac tissues in a concentration-dependent manner. These results suggest that the different electrical responses to O(2) ([Symbol: see text]-) in different cardiac regions may result from the regional differences in the SOD activity, thereby enhancing the regional electrical heterogeneity.
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PMID:Regional differences of superoxide dismutase activity enhance the superoxide-induced electrical heterogeneity in rabbit hearts. 1587 Sep 56