INT14902

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Context Info
Confidence 0.55
First Reported 1991
Last Reported 2010
Negated 1
Speculated 0
Reported most in Body
Documents 38
Total Number 42
Disease Relevance 24.19
Pain Relevance 2.86

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

cytosol (XDH) small molecule metabolic process (XDH) extracellular region (XDH)
peroxisome (XDH) cytoplasm (XDH)
Anatomy Link Frequency
renal tubule 1
plasma 1
muscle 1
cleavage 1
left coronary artery 1
XDH (Homo sapiens)
Pain Link Frequency Relevance Heat
withdrawal 11 99.84 Very High Very High Very High
Paracetamol 6 99.00 Very High Very High Very High
dexamethasone 7 98.68 Very High Very High Very High
alcohol 58 98.58 Very High Very High Very High
cINOD 69 98.24 Very High Very High Very High
corticosteroid 17 98.08 Very High Very High Very High
aspirin 26 97.30 Very High Very High Very High
ischemia 14 94.08 High High
vincristine 4 94.04 High High
adenocard 22 93.76 High High
Disease Link Frequency Relevance Heat
Syndrome 71 99.92 Very High Very High Very High
Myocardial Infarction 114 99.88 Very High Very High Very High
Crystal Associated Disease 1400 99.36 Very High Very High Very High
Iron Overload 1 99.36 Very High Very High Very High
Toxicity 53 99.18 Very High Very High Very High
Disease 172 99.02 Very High Very High Very High
Liver Disease 6 98.40 Very High Very High Very High
Hyponatremia 2 98.28 Very High Very High Very High
Coronary Heart Disease 12 98.24 Very High Very High Very High
Hyperuricemia 736 98.16 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Our data showed that Geum quellyon extract, containing tannins, exhibits interesting antioxidant properties, expressed by its capacity to scavenge 1,1-diphenyl-2-picryl-hydrazyl radical (DPPH) and superoxide anion (O(2)*-), to inhibit xanthine oxidase activity, to chelate metals, and to protect plasmid DNA from cleavage induced by hydroxyl radicals (*OH) and nitric oxide (NO).
Negative_regulation (inhibit) of xanthine oxidase in cleavage
1) Confidence 0.55 Published 2005 Journal J Ethnopharmacol Section Abstract Doc Link 15941635 Disease Relevance 1.22 Pain Relevance 0.22
The molecular mechanism of inhibition of XO activity by febuxostat (Adenuric®, Ipsen, Paris, France) is by high affinity binding to the enzyme in a molecular channel leading to the molybdenum-pterin active site, whereas allopurinol exerts relatively weak competitive inhibition on activity of only the oxidized form of XO (Okamoto et al 2003; Takano et al 2005).
Negative_regulation (inhibition) of XO
2) Confidence 0.48 Published 2008 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2643102 Disease Relevance 0.20 Pain Relevance 0
The mechanism by which XOR catalyzes hypoxanthine and xanthine conversion is extremely complex and has been previously described in detail.16,28 A fully reduced XO contains six electrons and its re-oxidation involves electron transfer to oxygen molecules which generates two H2O2 and two O2– species28 for every fully reduced XO molecule (Figure 1).
Negative_regulation (reduced) of XO
3) Confidence 0.47 Published 2009 Journal Vascular Health and Risk Management Section Body Doc Link PMC2672460 Disease Relevance 0.23 Pain Relevance 0.03
Nabumetone did not inhibit O2- generation in the xanthine-xanthine oxidase system.
Negative_regulation (inhibit) of xanthine-xanthine oxidase
4) Confidence 0.43 Published 2003 Journal J. Pharm. Pharmacol. Section Abstract Doc Link 12635655 Disease Relevance 0.28 Pain Relevance 0.20
Pre-treatment of the patients with a xanthine oxidase inhibitor influences radical production, indicating that oxidation of accumulated hypoxanthine has a role to play in this process.
Negative_regulation (inhibitor) of xanthine oxidase
5) Confidence 0.42 Published 2007 Journal International Journal of Medical Sciences Section Body Doc Link PMC1868659 Disease Relevance 0.54 Pain Relevance 0
The 13 patients included in the present study were identical to the control group in our previous work concerning the effects of pre-treatment with a xanthine oxidase inhibitor on free radical levels during carotid endarterectomy in patients operated on for symptomatic carotid artery stenosis 2.
Negative_regulation (inhibitor) of xanthine oxidase in carotid artery associated with carotid stenosis
6) Confidence 0.42 Published 2007 Journal International Journal of Medical Sciences Section Body Doc Link PMC1868659 Disease Relevance 0.64 Pain Relevance 0.16
The mechanism by which XOR catalyzes hypoxanthine and xanthine conversion is extremely complex and has been previously described in detail.16,28 A fully reduced XO contains six electrons and its re-oxidation involves electron transfer to oxygen molecules which generates two H2O2 and two O2– species28 for every fully reduced XO molecule (Figure 1).
Negative_regulation (reduced) of XO
7) Confidence 0.41 Published 2009 Journal Vascular Health and Risk Management Section Body Doc Link PMC2672460 Disease Relevance 0.34 Pain Relevance 0.03
More recently, Okamoto and Nishino have reported that XOR inhibitors can be categorized into different types according to the crystal structure of the various inhibitors binding to XOR (Okamoto and Nishino 2008).
Negative_regulation (inhibitors) of XOR
8) Confidence 0.36 Published 2008 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2643102 Disease Relevance 0.06 Pain Relevance 0
The urate-lowering therapy allopurinol, a xanthine oxidase (XO) inhibitor, has been the mainstay of prophylactic treatment for gout and conditions associated with hyperuricemia for many years (Wortmann 2002).
Negative_regulation (inhibitor) of XO associated with hyperuricemia and crystal associated disease
9) Confidence 0.36 Published 2008 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2643102 Disease Relevance 1.03 Pain Relevance 0
This phenomenon refers to an imbalance between left ventricular performance and myocardial energy consumption.75 The role of XO inhibition may either be to maintain cardiac output while reducing myocardial oxygen consumption or even increase cardiac output without increasing myocardial oxygen consumption.
Negative_regulation (inhibition) of XO
10) Confidence 0.35 Published 2009 Journal Vascular Health and Risk Management Section Body Doc Link PMC2672460 Disease Relevance 0.59 Pain Relevance 0.12
Allopurinol directly scavenges free radicals as demonstrated by Das et al and others66–68 in in vitro hearts where evidence of free radical scavenging occurred in the absence of XO activity.
Negative_regulation (absence) of XO in hearts
11) Confidence 0.35 Published 2009 Journal Vascular Health and Risk Management Section Body Doc Link PMC2672460 Disease Relevance 0.62 Pain Relevance 0.05
Febuxostat, a new xanthine oxidase inhibitor, is welcomed, as few alternatives for allopurinol are available.
Negative_regulation (inhibitor) of xanthine oxidase
12) Confidence 0.31 Published 2010 Journal Clin Interv Aging Section Abstract Doc Link PMC2817937 Disease Relevance 0.59 Pain Relevance 0.07
Febuxostat is a new selective inhibitor of xanthine oxidase.
Negative_regulation (inhibitor) of xanthine oxidase
13) Confidence 0.31 Published 2010 Journal Clin Interv Aging Section Body Doc Link PMC2817937 Disease Relevance 0.19 Pain Relevance 0.04
Just as in allopurinol, an important drug–drug interaction can occur with mercaptopurine and azathioprine due to inhibition of xanthine oxidase.
Negative_regulation (inhibition) of xanthine oxidase
14) Confidence 0.31 Published 2010 Journal Clin Interv Aging Section Body Doc Link PMC2817937 Disease Relevance 0 Pain Relevance 0
More recently, Zhao et al (2008) reported the effects of chronic XO inhibition by febuxostat or allopurinol on the progression of chronic heart failure (CHF) induced by left coronary artery ligation in rabbits, which have low intrinsic myocardial XO activity similar to humans.
Negative_regulation (inhibition) of XO in left coronary artery associated with myocardial infarction
15) Confidence 0.31 Published 2008 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2643102 Disease Relevance 1.16 Pain Relevance 0.03
Febuxostat is a novel potent selective inhibitor of XO that appears to be well tolerated in all groups of patients, including those who are sensitive to allopurinol.


Negative_regulation (inhibitor) of XO
16) Confidence 0.31 Published 2008 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2643102 Disease Relevance 0.98 Pain Relevance 0
It is a selective inhibitor of XO that has been developed for the treatment of hyperuricemia and gout, as it was found to have a potent inhibitory activity for XO/xanthine dehydrogenase (XDH) during evaluation of a range of newly synthesized molecules (Komoriya et al 1993).
Negative_regulation (inhibitor) of XO associated with hyperuricemia and crystal associated disease
17) Confidence 0.31 Published 2008 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2643102 Disease Relevance 0.58 Pain Relevance 0
Febuxostat was shown to inhibit both the oxidized and reduced forms of XO, unlike allopurinol and oxypurinol, each of which binds only to one form of the enzyme (Okamoto et al 2003; Takano et al 2005).
Negative_regulation (inhibit) of XO
18) Confidence 0.31 Published 2008 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2643102 Disease Relevance 0.22 Pain Relevance 0
Treatment with febuxostat initiated shortly after myocardial infarction delayed or prevented the onset of CHF, but XO inhibition with either drug initiated after establishment of the disease had no cardiac protection effects (Zhao et al 2008).


Negative_regulation (inhibition) of XO associated with disease and myocardial infarction
19) Confidence 0.31 Published 2008 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2643102 Disease Relevance 0.77 Pain Relevance 0
Further evidence for a possible direct antioxidant effect of allopurinol comes from models of experimental colitis where tungsten (a potent XO inhibitor) failed to improve symptoms whereas allopurinol did.69 Augustin et al suggested that this direct effect was only seen at higher doses.70 This was also seen in mice paracetamol toxicity models where lower doses (sufficient to block XO activity) of allopurinol failed to show antioxidant protection but higher doses did.71 There have been other non-XO effects of allopurinol suggested such as copper chelation, preventing LDL oxidation as described above,72 inhibition of heat shock protein (hsp) expression73 and calcium sensitization (below).
Negative_regulation (block) of XO associated with colitis, toxicity, paracetamol and shock
20) Confidence 0.30 Published 2009 Journal Vascular Health and Risk Management Section Body Doc Link PMC2672460 Disease Relevance 0.56 Pain Relevance 0.13

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