INT18883

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Context Info
Confidence 0.56
First Reported 1982
Last Reported 2010
Negated 0
Speculated 1
Reported most in Abstract
Documents 53
Total Number 54
Disease Relevance 21.14
Pain Relevance 57.52

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

nucleoplasm (RYBP) nucleus (RYBP) intracellular (RYBP)
DNA binding (RYBP) cytoplasm (RYBP)
Anatomy Link Frequency
liver 9
plasma 4
urine 2
enterocytes 1
Hepa 1-6 1
RYBP (Homo sapiens)
Pain Link Frequency Relevance Heat
Paracetamol 828 100.00 Very High Very High Very High
Leflunomide 16 97.84 Very High Very High Very High
alcohol 6 97.62 Very High Very High Very High
Analgesic 10 96.48 Very High Very High Very High
dexamethasone 5 93.92 High High
Bile 10 93.76 High High
adenocard 2 92.20 High High
cva 1 91.32 High High
addiction 1 89.84 High High
Glutamate 2 87.40 High High
Disease Link Frequency Relevance Heat
Hepatotoxicity 90 100.00 Very High Very High Very High
Nephrotoxicity 45 100.00 Very High Very High Very High
Rheumatoid Arthritis 30 99.98 Very High Very High Very High
Injury 36 99.78 Very High Very High Very High
Sprains And Strains 8 99.68 Very High Very High Very High
Nash(non-alcoholic Steatohepatitis) 12 99.52 Very High Very High Very High
Necrosis 27 98.80 Very High Very High Very High
Apoptosis 14 98.72 Very High Very High Very High
Disease Progression 1 98.32 Very High Very High Very High
Targeted Disruption 2 97.92 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
APAP uridine diphosphoglucuronyltransferase activity in rat hepatic microsomes was competitively inhibited by RA (0.1-2 mM).
Negative_regulation (inhibited) of APAP uridine diphosphoglucuronyltransferase associated with paracetamol and rheumatoid arthritis
1) Confidence 0.56 Published 1988 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 3133464 Disease Relevance 0.83 Pain Relevance 1.64
The Ki apparent for RA inhibition of APAP uridine diphosphoglucuronyltransferase was 0.04 mM.
Negative_regulation (inhibition) of APAP uridine diphosphoglucuronyltransferase associated with paracetamol and rheumatoid arthritis
2) Confidence 0.56 Published 1988 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 3133464 Disease Relevance 0.80 Pain Relevance 1.59
The substrate inhibition is confirmed by employing stable isotope-labeled APAP as the substrate, while APAP glucuronide is used to test for inhibition of d4-APAP glucuronide.
Negative_regulation (inhibition) of APAP associated with paracetamol
3) Confidence 0.48 Published 2006 Journal Chem. Res. Toxicol. Section Abstract Doc Link 16696573 Disease Relevance 0.33 Pain Relevance 1.45
In contrast, neither APAP nor 4-nitrophenol sulfotransferase activity in rat hepatic cytosol was inhibited by RA at concentrations up to 5 mM.
Negative_regulation (inhibited) of APAP associated with paracetamol and rheumatoid arthritis
4) Confidence 0.41 Published 1988 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 3133464 Disease Relevance 0.78 Pain Relevance 1.56
These results suggest that protection afforded by probenecid in vivo could be a consequence of the inhibition of APAP S-conjugate renal uptake and/or an increase in APAP renal clearance.
Negative_regulation (inhibition) of APAP associated with paracetamol
5) Confidence 0.40 Published 1998 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 9454804 Disease Relevance 0.14 Pain Relevance 1.43
Similar 8-hour temperature reduction for APAP-CR (one dose) and APAP-IR (two doses) demonstrates the efficacy of APAP-CR as an antipyretic in children 2 to 11 years of age.
Negative_regulation (reduction) of APAP-CR associated with paracetamol
6) Confidence 0.39 Published 2000 Journal J Clin Pharmacol Section Abstract Doc Link 10761163 Disease Relevance 0.20 Pain Relevance 1.21
Similar 8-hour temperature reduction for APAP-CR (one dose) and APAP-IR (two doses) demonstrates the efficacy of APAP-CR as an antipyretic in children 2 to 11 years of age.
Negative_regulation (reduction) of APAP-IR associated with paracetamol
7) Confidence 0.39 Published 2000 Journal J Clin Pharmacol Section Abstract Doc Link 10761163 Disease Relevance 0.20 Pain Relevance 1.21
Specifically, we observe that a small dose of alcohol (the equivalent of 1 ounce of ethanol), consumed over a period of one hour prior to the ingestion of APAP, leads to a reduction in APAP-mercapturic acid excretion.
Negative_regulation (reduction) of APAP associated with paracetamol and alcohol
8) Confidence 0.38 Published 1982 Journal Res. Commun. Chem. Pathol. Pharmacol. Section Abstract Doc Link 7146622 Disease Relevance 0.35 Pain Relevance 1.04
Mechanism-based inhibition incubations performed in mouse and human liver microsomes (MLM and HLM) indicated that inhibition of APAP bioactivation to NAPQI was observed in MLM but not in HLM.
Negative_regulation (inhibition) of APAP in liver associated with paracetamol
9) Confidence 0.31 Published 2008 Journal Toxicol. Lett. Section Abstract Doc Link 18588957 Disease Relevance 0.46 Pain Relevance 1.28
When APAP and LEF were incubated with human recombinant P450 enzymes, CYP1A2 was found to be the isozyme responsible for the inhibition of APAP bioactivation.
Negative_regulation (inhibition) of APAP associated with paracetamol and leflunomide
10) Confidence 0.31 Published 2008 Journal Toxicol. Lett. Section Abstract Doc Link 18588957 Disease Relevance 0.40 Pain Relevance 1.26
Quantification of major APAP metabolites in plasma showed that APAP-glutathione (GSH), a conjugate generated via metabolic activation of APAP, was reduced significantly while APAP-sulfate and APAP-glucuronide, detoxified metabolites both produced directly from the parent drug, were increased in mice pretreated with DMSO.
Negative_regulation (reduced) of APAP in plasma associated with paracetamol
11) Confidence 0.28 Published 2006 Journal Biol. Pharm. Bull. Section Abstract Doc Link 16880615 Disease Relevance 0.26 Pain Relevance 0.92
Biochemical alterations to cellular proteolytic events were also found in vivo, including APAP- or AMAP-mediated inhibition of caspase-3 processing.
Negative_regulation (inhibition) of APAP
12) Confidence 0.28 Published 2002 Journal Biochem. Pharmacol. Section Abstract Doc Link 12147292 Disease Relevance 0.74 Pain Relevance 0.24
The data indicated decreased liver APAP content and glutathione consumption.
Negative_regulation (decreased) of APAP in liver associated with paracetamol
13) Confidence 0.26 Published 2009 Journal Biochem. Pharmacol. Section Abstract Doc Link 19426699 Disease Relevance 0.19 Pain Relevance 1.19
Our findings indicate that CYP3A4, the major P450 isoform in human liver and enterocytes, contributes appreciably to the formation of the cytotoxic metabolite NAPQI at therapeutically relevant concentrations of APAP and suggest that APAP may be a previously unrecognized inhibitor of this enzyme.
Negative_regulation (inhibitor) of APAP in enterocytes associated with paracetamol
14) Confidence 0.25 Published 1993 Journal Biochem. Pharmacol. Section Abstract Doc Link 8387297 Disease Relevance 0 Pain Relevance 0.52
Therefore, the BNPP-induced reduction in APAP-induced nephrotoxicity appears to be due to inhibition of APAP deacetylation.
Negative_regulation (inhibition) of APAP associated with nephrotoxicity and paracetamol
15) Confidence 0.21 Published 1985 Journal Toxicol. Appl. Pharmacol. Section Abstract Doc Link 4082192 Disease Relevance 0.58 Pain Relevance 1.19
Thus, the greater hepatotoxicity of APAP administered at 20:00 h appears to be related to the marked decrease in hepatic GSH at this time period, whereas the simultaneous reduction in APAP activation may be responsible for the lack of hepatotoxicity in mice treated with this analgesic at 14:00 h.
Negative_regulation (reduction) of APAP associated with paracetamol, analgesic and hepatotoxicity
16) Confidence 0.18 Published 1998 Journal Toxicology Section Abstract Doc Link 9704905 Disease Relevance 0.36 Pain Relevance 1.17
BNPP (1 to 8 mM) reduced APAP deacetylation and covalent binding in F344 renal cortical homogenates in a concentration-dependent manner.
Negative_regulation (reduced) of APAP associated with paracetamol
17) Confidence 0.15 Published 1985 Journal Toxicol. Appl. Pharmacol. Section Abstract Doc Link 4082192 Disease Relevance 0.59 Pain Relevance 1.11
Pretreatment of animals with BNPP prior to APAP or PAP administration resulted in marked reduction of APAP (900 mg/kg) nephrotoxicity but not PAP nephrotoxicity.
Negative_regulation (reduction) of APAP associated with nephrotoxicity and paracetamol
18) Confidence 0.13 Published 1985 Journal Toxicol. Appl. Pharmacol. Section Abstract Doc Link 4082192 Disease Relevance 0.60 Pain Relevance 1.27
Thus, strain differences in APAP nephrotoxicity decrease with advancing age.
Negative_regulation (decrease) of APAP associated with nephrotoxicity, paracetamol and sprains and strains
19) Confidence 0.13 Published 1989 Journal Fundam Appl Toxicol Section Abstract Doc Link 2925021 Disease Relevance 1.64 Pain Relevance 0.83
PEITC treatment also significantly decreased the plasma levels of oxidized APAP metabolites (analyzed as APAP-glutathione, APAP-cysteine, and APAP-N-acetylcysteine) and reduced the urinary excretion of APAP-cysteine.
Negative_regulation (decreased) of APAP in plasma associated with paracetamol
20) Confidence 0.13 Published 1997 Journal Toxicol. Appl. Pharmacol. Section Abstract Doc Link 9194414 Disease Relevance 0.50 Pain Relevance 1.41

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