INT91676

Context Info Confidence 0.58 First Reported 2000 Last Reported 2010 Negated 0 Speculated 2 Reported most in Body Documents 8 Total Number 22 Disease Relevance 2.36 Pain Relevance 0.93

oxidoreductase activity (Cyp3a2) endoplasmic reticulum (Cyp3a2) enzyme binding (Cyp3a2) cytoplasm (Cyp3a2)

Anatomy Link Frequency fat 2 hepatocytes 1 Cyp3a2 (Rattus norvegicus)

Pain Link Frequency Relevance Heat Analgesic 3 92.12 Inflammatory mediators 13 90.64 lidocaine 9 90.08 addiction 1 72.12 cytokine 13 56.72 Oxycodone 12 50.00 Kinase C 13 17.60 ketamine 13 5.00 anesthesia 13 5.00 Inflammation 13 5.00

Disease Link Frequency Relevance Heat Infection 130 99.70 Diabetes Mellitus 14 99.54 Adenovirus Infection 91 93.84 INFLAMMATION 39 90.24 Toxicity 52 89.76 Targeted Disruption 13 76.88 Acute Liver Failure 3 75.00 Hepatotoxicity 39 66.68 Heart Rate Under Development 26 5.00 Viral Infection 26 5.00

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

The observed changes indicate an impairment of N-deethylation metabolic pathway in streptozotocin-induced diabetic rats, i.e. a possible decrease in the enzymatic activity of CYP3A2 and CYP1A2.

Spec (possible) Negative_regulation (decrease) of CYP3A2 associated with diabetes mellitus

1) Confidence 0.58 Published 2006 Journal J. Pharm. Pharmacol. Section Abstract Doc Link 16872554 Disease Relevance 0.63 Pain Relevance 0.28

Immunoblotting assays demonstrated a corresponding significant elevation of rGSTA5 protein and repression of CYP3A2 protein.

Negative_regulation (repression) of CYP3A2 protein

2) Confidence 0.58 Published 2010 Journal J. Pharm. Pharmacol. Section Body Doc Link 20487198 Disease Relevance 0 Pain Relevance 0

The observed changes indicate an impairment of N-deethylation, i.e. a possible decrease in enzymatic activity of CYP3A2 and CYP1A2, which are the major enzymes catalyzing this reaction.

Spec (possible) Negative_regulation (decrease) of CYP3A2

3) Confidence 0.57 Published 2003 Journal Pol J Pharmacol Section Abstract Doc Link 12926555 Disease Relevance 0.47 Pain Relevance 0.25

The CYP3A2 mRNA levels decreased (P <.05) in the rats fed ethanol-containing diets by 73 to 83% compared with rats fed control diets, regardless of the CHO/fat ratio.

Negative_regulation (decreased) of CYP3A2 in fat

4) Confidence 0.54 Published 2000 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 11046114 Disease Relevance 0 Pain Relevance 0.08

These results indicate that 1) ethanol differentially affects the expression of CYP3A gene family and this regulation appears to be modulated by dietary CHO/fat ratio; 2) the decrease in testosterone 6 beta-hydroxylase activity and CYP3A apoprotein levels are most likely due to the ethanol-induced decrease in CYP3A2 mRNA levels; and 3) CYP3A9 is induced by ethanol and is a low-affinity, high-K(m) chlorzoxazone hydroxylase.

Negative_regulation (decrease) of CYP3A2 in fat

5) Confidence 0.54 Published 2000 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 11046114 Disease Relevance 0 Pain Relevance 0

The serum AST activities corresponding to a 50% decrease of CYP2C 11, CYP2E1, CYP3A2 and CYP1A2 activities were about 710, 780, 1030 and 1300 IU/l, respectively.

Negative_regulation (decrease) of CYP3A2

6) Confidence 0.53 Published 2004 Journal Int J Pharm Section Abstract Doc Link 14706259 Disease Relevance 0.15 Pain Relevance 0.08

Treatment of primary hepatocytes with a peptide known to block integrin receptors and prevent adenoviral infection significantly reduced CYP3A2 activity with respect to untreated controls (Figure 10).

Negative_regulation (reduced) of CYP3A2 in hepatocytes associated with infection

7) Confidence 0.49 Published 2008 Journal Virol J Section Body Doc Link PMC2565663 Disease Relevance 0.10 Pain Relevance 0

In addition, the microsomal activity of CYP3A2, measured via 6beta-hydroxylation of testosterone, was significantly decreased in oxycodone-treated rats.

Negative_regulation (decreased) of CYP3A2

8) Confidence 0.43 Published 2010 Journal J. Pharm. Pharmacol. Section Body Doc Link 20487198 Disease Relevance 0 Pain Relevance 0

CONCLUSIONS: Repeated oxycodone administration is associated with a significant up-regulation of rGSTA5 and concomitant down-regulation of CYP3A2 mRNA, protein expression and functionality.

Negative_regulation (regulation) of CYP3A2

9) Confidence 0.43 Published 2010 Journal J. Pharm. Pharmacol. Section Body Doc Link 20487198 Disease Relevance 0 Pain Relevance 0

Chronic intragastric infusion of ethanol-containing diets induces CYP3A9 while decreasing CYP3A2 in male rats.

Negative_regulation (decreasing) of CYP3A2

10) Confidence 0.40 Published 2000 Journal J. Pharmacol. Exp. Ther. Section Title Doc Link 11046114 Disease Relevance 0 Pain Relevance 0.09

CYP3A2 mRNA levels of animals treated with the wild-type virus were consistently suppressed throughout the duration of the study.

Negative_regulation (suppressed) of CYP3A2 mRNA

11) Confidence 0.36 Published 2008 Journal Virol J Section Body Doc Link PMC2565663 Disease Relevance 0 Pain Relevance 0

Administration of active viruses also significantly reduced hepatic CYP3A2 mRNA as early as six hours after administration.

Negative_regulation (reduced) of CYP3A2 mRNA

12) Confidence 0.36 Published 2008 Journal Virol J Section Body Doc Link PMC2565663 Disease Relevance 0 Pain Relevance 0

At later timepoints, CYP mRNA levels were suppressed in animals given HDAd in a manner similar not only to the first generation virus, but to that of wild type virus, containing all viral genetic elements, suggesting that transcription and expression of viral genes cannot fully account for the observed reduction of CYP3A2.

Negative_regulation (reduction) of CYP3A2

13) Confidence 0.36 Published 2008 Journal Virol J Section Body Doc Link PMC2565663 Disease Relevance 0.12 Pain Relevance 0

CYP3A2 activity was reduced by 20% in animals given the UVAd vector at the same timepoint (Figure 2B, p ?

Negative_regulation (reduced) of CYP3A2

14) Confidence 0.36 Published 2008 Journal Virol J Section Body Doc Link PMC2565663 Disease Relevance 0 Pain Relevance 0

Six hours after administration, CYP3A2 activity was suppressed by approximately 41%, in each treatment group with respect to that of saline treated animals (Figure 2A, p ?

Negative_regulation (suppressed) of CYP3A2

15) Confidence 0.36 Published 2008 Journal Virol J Section Body Doc Link PMC2565663 Disease Relevance 0 Pain Relevance 0

Administration of helper-dependent adenovirus (HDAd), devoid of all viral genes and significantly less immunogenic than wild type or first generation adenoviruses [17,23], suppressed CYP3A2 protein, activity, and gene expression for 14 days (Figures 1, 2, 3, p ?

Negative_regulation (suppressed) of CYP3A2 protein

16) Confidence 0.36 Published 2008 Journal Virol J Section Body Doc Link PMC2565663 Disease Relevance 0.17 Pain Relevance 0.03

Fourteen days after a single dose of virus, CYP3A2 activity continued to be reduced in each treatment group.

Negative_regulation (reduced) of CYP3A2

17) Confidence 0.36 Published 2008 Journal Virol J Section Body Doc Link PMC2565663 Disease Relevance 0 Pain Relevance 0

Inactivated virus suppressed CYP3A2 activity by 25–50% for 14 days (p ?

Negative_regulation (suppressed) of CYP3A2

18) Confidence 0.36 Published 2008 Journal Virol J Section Abstract Doc Link PMC2565663 Disease Relevance 0.12 Pain Relevance 0.03

In a manner similar to protein expression, the wild-type virus induced the most significant suppression of CYP3A2 activity four days after administration.

Negative_regulation (suppression) of CYP3A2

19) Confidence 0.36 Published 2008 Journal Virol J Section Body Doc Link PMC2565663 Disease Relevance 0 Pain Relevance 0

Given that CYP3A2 continued to be suppressed in all groups given active virus beyond 24 hours, we believe that changes in CYP3A2 expression and function may not be mediated by changes in PXR during adenovirus infection.

Negative_regulation (suppressed) of CYP3A2 associated with adenovirus infection

20) Confidence 0.36 Published 2008 Journal Virol J Section Body Doc Link PMC2565663 Disease Relevance 0.31 Pain Relevance 0

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