INT20303

Context Info Confidence 0.61 First Reported 1990 Last Reported 2010 Negated 2 Speculated 0 Reported most in Abstract Documents 11 Total Number 11 Disease Relevance 2.46 Pain Relevance 3.84

mitochondrion (Cyp2e1) oxidoreductase activity (Cyp2e1) endoplasmic reticulum (Cyp2e1) enzyme binding (Cyp2e1)

Anatomy Link Frequency liver 2 Cyp2e1 (Rattus norvegicus)

Pain Link Frequency Relevance Heat Paracetamol 198 99.32 Bioavailability 4 96.12 monoamine 1 90.84 anticonvulsant 1 90.68 carbamazepine 3 81.64 halothane 3 79.68 Analgesic 3 79.08 topical agent 4 5.00 cINOD 3 5.00 Inflammation 3 5.00

Disease Link Frequency Relevance Heat Toxicity 39 98.76 Hepatotoxicity 17 98.00 Starvation 2 91.12 Diabetes Mellitus 4 91.00 Stress 9 88.40 Death 50 78.60 Aging 22 74.60 Liver Failure 2 70.68 Apoptosis 16 50.00 Mucositis 1 43.28

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

CYP2E1 is developmentally regulated, under liver-specific control, and undergoes substrate-induced protein stabilization.

Regulation (regulated) of CYP2E1 in liver

1) Confidence 0.61 Published 2007 Journal Drug Metab. Dispos. Section Abstract Doc Link 17020953 Disease Relevance 0.35 Pain Relevance 0.33

Transcriptional and posttranscriptional regulation of CYP2E1, an N-nitrosodimethylamine demethylase.

Regulation (regulation) of CYP2E1

2) Confidence 0.60 Published 1990 Journal Int. Symp. Princess Takamatsu Cancer Res. Fund Section Title Doc Link 2134674 Disease Relevance 0 Pain Relevance 0.20

Three weeks later, the rats were either sacrificed for an in vitro metabolism study or challenged with 0.50 g/kg CCl(4) p.o. or 0.75 g/kg APAP i.p.TRZ at 100 and 500 mg/kg/rat increased the CYP3A level as well as the testosterone 6beta-hydroxylation activities in liver microsomes, but did not affect CYP2E1.

Neg (not) Regulation (affect) of CYP2E1 in liver associated with paracetamol

3) Confidence 0.57 Published 2002 Journal Toxicology Section Abstract Doc Link 12062933 Disease Relevance 0.54 Pain Relevance 0.50

In adult animals, CYP2E1 is posttranscriptionally regulated through mRNA and protein stabilization.

Regulation (regulated) of CYP2E1

4) Confidence 0.44 Published 1990 Journal Int. Symp. Princess Takamatsu Cancer Res. Fund Section Abstract Doc Link 2134674 Disease Relevance 0 Pain Relevance 0.19

To determine if this increase in ROS production was related to AAP-induced CYP2E1 activity and caused a decrease in GSH levels, we studied the effect of NAC and of the CYP2E1 inhibitor TTD.

Regulation (effect) of CYP2E1 associated with paracetamol

5) Confidence 0.41 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3000821 Disease Relevance 0.34 Pain Relevance 0.90

The role of diet and ethanol induction and inhibition on CYP2E1, the enzyme of greatest interest for acetaminophen is multifaceted.

Regulation (role) of CYP2E1 associated with paracetamol

6) Confidence 0.38 Published 2002 Journal J. Toxicol. Clin. Toxicol. Section Abstract Doc Link 11990202 Disease Relevance 0.40 Pain Relevance 0.54

The PB-induced up-regulation of CYP2B, CYP2E1 and CYP1A1 isozymes was markedly higher in CD than in NF rats.

Regulation (regulation) of CYP2E1

7) Confidence 0.38 Published 2009 Journal J Appl Toxicol Section Abstract Doc Link 18798224 Disease Relevance 0 Pain Relevance 0.62

The mechanism of regulation CYP2E1 and its role in acetaminophen toxicity will be discussed.

Regulation (regulation) of CYP2E1 associated with toxicity and paracetamol

8) Confidence 0.27 Published 2007 Journal Drug Metab. Dispos. Section Abstract Doc Link 17020953 Disease Relevance 0.41 Pain Relevance 0.34

For example, a previous report showed changes in male rat hepatic Cyp2e1 activity between 3 and 18 months of age despite the relative stasis of mRNA and protein levels [44].

Regulation (changes) of Cyp2e1

9) Confidence 0.19 Published 2010 Journal BMC Genomics Section Body Doc Link PMC3012673 Disease Relevance 0.24 Pain Relevance 0

Although probably best recognized as an inhibitor of drug metabolism, isoniazid has a biphasic effect of inhibition-induction on one cytochrome P450 isozyme, CYP2E1, which partially explains the interaction with acetaminophen and increased risk of hepatotoxicity.

Regulation (effect) of CYP2E1 associated with paracetamol and hepatotoxicity

10) Confidence 0.11 Published 1999 Journal Am. J. Med. Sci. Section Abstract Doc Link 10334118 Disease Relevance 0.18 Pain Relevance 0.23

An evaluation of the effects of posaconazole on the various CYP450 enzymes demonstrated an inhibitory effect on CYP3A4 activity, but no influence on the activity of the other isoenzymes (CYP1A2, CYP2C8/9, CYP2D6 or CYP2E1) (Wexler et al 2004).

Neg (no) Regulation (influence) of CYP2E1

11) Confidence 0.04 Published 2007 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2374940 Disease Relevance 0 Pain Relevance 0

General Comments

This test has worked.