INT76025

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Context Info
Confidence 0.69
First Reported 1998
Last Reported 2009
Negated 2
Speculated 1
Reported most in Body
Documents 20
Total Number 22
Disease Relevance 5.88
Pain Relevance 6.91

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

oxidoreductase activity (Cyp3a11) endoplasmic reticulum (Cyp3a11)
Anatomy Link Frequency
liver 3
plasma 1
hepatocytes 1
CAR 1
intestine 1
Cyp3a11 (Mus musculus)
Pain Link Frequency Relevance Heat
alcohol 20 99.98 Very High Very High Very High
Paracetamol 86 99.56 Very High Very High Very High
withdrawal 3 99.44 Very High Very High Very High
dexamethasone 20 98.00 Very High Very High Very High
agonist 94 91.52 High High
Bile 415 87.76 High High
Potency 2 81.76 Quite High
Glutamate 1 74.52 Quite High
antidepressant 30 35.92 Quite Low
Inflammation 170 34.00 Quite Low
Disease Link Frequency Relevance Heat
Targeted Disruption 201 99.56 Very High Very High Very High
Hepatotoxicity 69 98.72 Very High Very High Very High
Toxicity 49 98.68 Very High Very High Very High
Disorder Of Lipid Metabolism 42 97.32 Very High Very High Very High
Severe Combined Immunodeficiency 12 95.68 Very High Very High Very High
Stress 12 92.84 High High
Apoptosis 50 90.96 High High
Diabetes Mellitus 30 84.00 Quite High
Colon Cancer 20 79.28 Quite High
Breast Cancer 82 73.56 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Activation of PXR represents an important mechanism for the induction of cytochrome P450 3A (CYP3A) enzymes that can convert acetaminophen (APAP) to its toxic intermediate metabolite, N-acetyl-p-benzoquinone imine (NAPQI).
Positive_regulation (induction) of cytochrome P450 3A associated with paracetamol
1) Confidence 0.69 Published 2004 Journal Toxicol. Sci. Section Abstract Doc Link 15456926 Disease Relevance 0.29 Pain Relevance 0.43
Activation of PXR represents an important mechanism for the induction of cytochrome P450 3A (CYP3A) enzymes that can convert acetaminophen (APAP) to its toxic intermediate metabolite, N-acetyl-p-benzoquinone imine (NAPQI).
Positive_regulation (induction) of CYP3A associated with paracetamol
2) Confidence 0.69 Published 2004 Journal Toxicol. Sci. Section Abstract Doc Link 15456926 Disease Relevance 0.30 Pain Relevance 0.43
Although this result suggests that CYP2E1 has a role in the different susceptibilities of these mouse lines, our findings that EIP-mediated increases in CYP3A activities were greater in wild-type mice compared with Cyp2e1(-/-) mice raises the possibility that differential increases in CYP3A may also contribute to the greater APAP sensitivity in EIP-pretreated wild-type mice.
Spec (possibility) Positive_regulation (increases) of CYP3A associated with paracetamol
3) Confidence 0.67 Published 2007 Journal Drug Metab. Dispos. Section Abstract Doc Link 17392391 Disease Relevance 0.46 Pain Relevance 0.99
Although this result suggests that CYP2E1 has a role in the different susceptibilities of these mouse lines, our findings that EIP-mediated increases in CYP3A activities were greater in wild-type mice compared with Cyp2e1(-/-) mice raises the possibility that differential increases in CYP3A may also contribute to the greater APAP sensitivity in EIP-pretreated wild-type mice.
Positive_regulation (increases) of CYP3A associated with paracetamol
4) Confidence 0.67 Published 2007 Journal Drug Metab. Dispos. Section Abstract Doc Link 17392391 Disease Relevance 0.47 Pain Relevance 0.99
However, CYP3A, which is also induced by alcohol, has been shown to have a greater affinity for acetaminophen than CYP2E.
Positive_regulation (induced) of CYP3A associated with paracetamol and alcohol
5) Confidence 0.56 Published 1998 Journal Biochem. Pharmacol. Section Abstract Doc Link 9633991 Disease Relevance 0.41 Pain Relevance 0.62
Despite a 2.5-fold higher level of total hepatic CYP3A protein and a 3.6-fold higher level of CYP3A activity compared to wild-type mice, PXR(-/-) mice were less sensitive to APAP hepatotoxicity.
Positive_regulation (level) of CYP3A associated with paracetamol and hepatotoxicity
6) Confidence 0.49 Published 2005 Journal Drug Metab. Dispos. Section Abstract Doc Link 16141365 Disease Relevance 0.51 Pain Relevance 0.82
Pretreatment of mice and rats with inducers of CYP3A increases acetaminophen (APAP) hepatotoxicity.
Positive_regulation (inducers) of CYP3A associated with paracetamol and hepatotoxicity
7) Confidence 0.46 Published 2005 Journal Drug Metab. Dispos. Section Abstract Doc Link 16141365 Disease Relevance 0.39 Pain Relevance 0.56
Targeted disruption of SXR abolishes the induction of CYP3A genes in response to prototypic inducers such as dexamethasone or PCN.
Positive_regulation (induction) of CYP3A associated with targeted disruption and dexamethasone
8) Confidence 0.46 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0.40 Pain Relevance 0.20
These models demonstrate convincingly that SXR is the key regulator of CYP3A induction by xenobiotics.
Positive_regulation (induction) of CYP3A
9) Confidence 0.46 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0 Pain Relevance 0
Constitutively active SXR (VP-SXR) transgenic mice showed sustained induction of CYP3A and CYP2B [Xie et al., 2000a; Xie et al., 2000b].
Positive_regulation (induction) of CYP3A associated with targeted disruption
10) Confidence 0.46 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0.19 Pain Relevance 0
Induction of CYP3A by some SXR ligands was positively correlated with induction of ApoA-I mRNA and plasma HDL and ApoA-I levels in mice [Bachmann et al., 2004].
Positive_regulation (Induction) of CYP3A in plasma associated with disorder of lipid metabolism
11) Confidence 0.46 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0.31 Pain Relevance 0.03
Differences in amino acid sequences among the mammalian receptors are responsible for species-specific induction of CYP3A by drugs and xenobiotics [LeCluyse, 2001; Watkins et al., 2001].
Positive_regulation (induction) of CYP3A
12) Confidence 0.46 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0.06 Pain Relevance 0
At the time of APAP administration, which followed an 11 h withdrawal from the alcohols, alcohol-induced levels of CYP3A were sustained in both mouse lines, whereas CYP2E1 was decreased to constitutive levels in wild-type mice.
Positive_regulation (induced) of CYP3A associated with paracetamol, withdrawal and alcohol
13) Confidence 0.45 Published 2007 Journal Drug Metab. Dispos. Section Abstract Doc Link 17392391 Disease Relevance 0.44 Pain Relevance 1.06
Analysis of phase I detoxification genes revealed that CYP1A2 and CYP3A11 were up-regulated in wild-type mice but down-regulated in RXRalpha-deficient mice after APAP administration.
Positive_regulation (up-regulated) of CYP3A11 associated with paracetamol
14) Confidence 0.44 Published 2004 Journal Mol. Pharmacol. Section Abstract Doc Link 14978233 Disease Relevance 0.26 Pain Relevance 0.39
Rifabutin, an analogue of rifampicin, also specifically induced h-CYP3A, but not the host murine Cyp3a, in the chimeric m-liver [27].
Neg (not) Positive_regulation (induced) of Cyp3a in liver
15) Confidence 0.38 Published 2009 Journal PPAR Research Section Body Doc Link PMC2768028 Disease Relevance 0.10 Pain Relevance 0.04
Rifabutin, an analogue of rifampicin, also specifically induced h-CYP3A, but not the host murine Cyp3a, in the chimeric m-liver [27].
Neg (not) Positive_regulation (induced) of CYP3A in liver
16) Confidence 0.33 Published 2009 Journal PPAR Research Section Body Doc Link PMC2768028 Disease Relevance 0.10 Pain Relevance 0.04
Corresponding induction of the SXR-inducible CYP3A genes in humans, rats and rabbits was also observed in primary hepatocytes.
Positive_regulation (induction) of CYP3A in hepatocytes
17) Confidence 0.31 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0.08 Pain Relevance 0
The crystal structure of the SXR LBD suggested which amino acid differences in the LBD of SXR contributed to species differences in ligand activation of human vs. mouse receptor and the consequent induction of CYP3A.
Positive_regulation (induction) of CYP3A
18) Confidence 0.31 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0.07 Pain Relevance 0
Furthermore, another study showed that the survival rate of mice receiving paraquat significantly rose with pretreatment with phenytoin, phenobarbital, or rifampicin, which induced activity in CYP3A, CYP2B, or CYP2C [Shimada et al., 2002].
Positive_regulation (induced) of CYP3A
19) Confidence 0.31 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0.48 Pain Relevance 0.03
Comparison of their responses to LCA treatment demonstrates that CAR predominantly mediates induction of the cytochrome p450 CYP3A11 and the multidrug resistance-associated protein 3 transporter, whereas PXR is the major regulator of the Na+-dependent organic anion transporter 2.
Positive_regulation (induction) of cytochrome p450 CYP3A11 in CAR
20) Confidence 0.22 Published 2004 Journal J. Biol. Chem. Section Abstract Doc Link 15358766 Disease Relevance 0.25 Pain Relevance 0.18

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