Details of Xenobiotics-DME Interaction (XEOTIC)

General Information of Drug-Metabolizing Enzyme (DME ID: DME0169)
DME Name Serum paraoxonase/arylesterase 1 (PON1), Homo sapiens DME Info
UniProt ID
PON1_HUMAN
EC Number    EC: 3.1.1.2     (Click to Show/Hide the Complete EC Tree)
Hydrolases
Ester bond hydrolase
Carboxylic ester hydrolase
EC: 3.1.1.2
Lineage    Species: Homo sapiens     (Click to Show/Hide the Complete Species Lineage)
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Interactome
Interactions between Xenobiotics and DME (XEOTIC)
      Health or Environmental Toxicant(s)
                  Acute Toxic Substance Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Mercury Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01509   XEOTIC Info Gene Form Protein
                                 Classification Acute Toxic Substance
                                 DME Modulation Mercury inhibits the drug-metabolizing activity of DME PON1 [1]
                  Carcinogen Click to Show/Hide the Full List of Xenobiotics:        3 Xenobiotics
                              Benzo(a)pyrene Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00898   XEOTIC Info Gene Form mRNA
                                 Classification Carcinogen
                                 DME Modulation Benzo(a)pyrene inhibits the expression of DME PON1 [2]
                              Methylcholanthrene Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00899   XEOTIC Info Gene Form Protein
                                 Classification Carcinogen
                                 DME Modulation Methylcholanthrene induces the drug-metabolizing activity of DME PON1 [3]
                              Aflatoxin B1 Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00806   XEOTIC Info Gene Form mRNA
                                 Classification Carcinogen-mycotoxin
                                 DME Modulation Aflatoxin B1 inhibits the expression of DME PON1 [4]
                  Health Hazard/Toxicant Click to Show/Hide the Full List of Xenobiotics:        3 Xenobiotics
                              3-methylquercetin Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01141   XEOTIC Info Gene Form mRNA
                                 Classification Health Hazard
                                 DME Modulation 3-methylquercetin up-regulates the expression of DME PON1 [5]
                              Lead Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01505   XEOTIC Info Gene Form Protein
                                 Classification Health Hazard
                                 DME Modulation Lead inhibits the drug-metabolizing activity of DME PON1 [6]
                              Pyruvaldehyde Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01448   XEOTIC Info Gene Form Protein
                                 Classification Health Hazard
                                 DME Modulation Pyruvaldehyde inhibits the drug-metabolizing activity of DME PON1 [7]
      Natural Product(s), Extract(s) or Medicine(s)
                  Natural Product Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Flavone Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01304   XEOTIC Info Gene Form mRNA
                                 Classification Natural Product
                                 DME Modulation Flavone up-regulates the expression of DME PON1 [8]
      Pharmaceutical Agent(s)
                  Approved/Marketed Drug Click to Show/Hide the Full List of Xenobiotics:      25 Xenobiotics
                              Acetaminophen Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00217   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Acetaminophen inhibits the expression of DME PON1 [9]
                              Ampicillin Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00096   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Ampicillin inhibits the drug-metabolizing activity of DME PON1 [10]
                              Aspirin Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00213   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Aspirin induces the drug-metabolizing activity of DME PON1 [11]
                              Atorvastatin Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00340   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Atorvastatin induces the drug-metabolizing activity of DME PON1 [12], [13]
                              Bosentan Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00148   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Bosentan inhibits the expression of DME PON1 [14]
                              Carbamazepine Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00011   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Carbamazepine inhibits the drug-metabolizing activity of DME PON1 [15]
                              Ciprofloxacin Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00349   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Ciprof DMEloxacin inhibits the drug-metabolizing activity of DME PON1 [10]
                              Copper Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00834   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Copper inhibits the drug-metabolizing activity of DME PON1 [16]
                              Copper sulfate Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00117   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Copper sulfate inhibits the expression of DME PON1 [17]
                              Cyclosporine Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00241   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Cyclosporine inhibits the expression of DME PON1 [2], [18]
                              Dexamethasone Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00088   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Dexamethasone induces the drug-metabolizing activity of DME PON1 [19]
                              Estradiol Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00090   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Estradiol inhibits the expression of DME PON1 [2]
                              Fenofibrate Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00035   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Fenofibrate induces the drug-metabolizing activity of DME PON1 [20]
                              Gabapentin Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00041   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Gabapentin inhibits the drug-metabolizing activity of DME PON1 [15]
                              Hydrogen peroxide Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00388   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Hydrogen peroxide inhibits the drug-metabolizing activity of DME PON1 [21], [22]
                              Nandrolone decanoate Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00418   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Nandrolone decanoate inhibits the expression of DME PON1 [23]
                              Omacor Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00194   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Omacor up-regulates the expression of DME PON1 [24]
                              Panobinostat Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00372   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Panobinostat inhibits the drug-metabolizing activity of DME PON1 [25]
                              Pitavastatin Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00376   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Pitavastatin up-regulates the expression of DME PON1 [26]
                              Sulfisoxazole acetyl Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00327   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Sulfisoxazole acetyl inhibits the drug-metabolizing activity of DME PON1 [27]
                              Valproic acid Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00029   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Valproic acid inhibits the expression of DME PON1 [28]
                              Vorinostat Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00079   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Vorinostat inhibits the expression of DME PON1 [29]
                              Calcium Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00832   XEOTIC Info Gene Form Protein
                                 Classification Drug Marketed but not Approved by US FDA
                                 DME Modulation Calcium induces the drug-metabolizing activity of DME PON1 [30]
                              Linoleic acid Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01367   XEOTIC Info Gene Form Protein
                                 Classification Drug Marketed but not Approved by US FDA
                                 DME Modulation Linoleic acid inhibits the drug-metabolizing activity of DME PON1 [21], [22]
                              Sulfisomidine Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01477   XEOTIC Info Gene Form Protein
                                 Classification Drug Marketed but not Approved by US FDA
                                 DME Modulation Sulfisomidine inhibits the drug-metabolizing activity of DME PON1 [31]
                  Drug in Phase 3 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Resveratrol Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00568   XEOTIC Info Gene Form Protein
                                 Classification Highest Clinical Status: Phase 3
                                 DME Modulation Resveratrol induces the drug-metabolizing activity of DME PON1 [32]
                  Drug in Phase 2 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        2 Xenobiotics
                              MS-275 Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00581   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 2
                                 DME Modulation MS-275 up-regulates the expression of DME PON1 [33]
                              NCX-4016 Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00624   XEOTIC Info Gene Form Protein
                                 Classification Highest Clinical Status: Phase 2
                                 DME Modulation NCX-4016 induces the drug-metabolizing activity of DME PON1 [34]
                  Drug in Phase 1 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        2 Xenobiotics
                              Naringenin Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00573   XEOTIC Info Gene Form Protein
                                 Classification Highest Clinical Status: Phase 1
                                 DME Modulation Naringenin induces the drug-metabolizing activity of DME PON1 [35]
                              Palmitoleic acid Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01421   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 1
                                 DME Modulation Palmitoleic acid inhibits the expression of DME PON1 [36], [37]
                  Preclinical/Patented Drug Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              GW-4064 Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00735   XEOTIC Info Gene Form mRNA
                                 Classification Patented Pharmaceutical Agent
                                 DME Modulation GW-4064 inhibits the expression of DME PON1 [38]
                  Investigative Agent Click to Show/Hide the Full List of Xenobiotics:        3 Xenobiotics
                              4-hydroxy-2-nonenal Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00869   XEOTIC Info Gene Form Protein
                                 Classification Investigative Agent
                                 DME Modulation 4-hydroxy-2-nonenal inhibits the drug-metabolizing activity of DME PON1 [21]
                              Arachidonic acid Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00876   XEOTIC Info Gene Form Protein
                                 Classification Investigative Agent
                                 DME Modulation Arachidonic acid inhibits the drug-metabolizing activity of DME PON1 [21]
                              Egtazic acid Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01286   XEOTIC Info Gene Form Protein
                                 Classification Investigative Agent
                                 DME Modulation Egtazic acid inhibits the drug-metabolizing activity of DME PON1 [30]
References
1 Mechanisms of cholinesterase inhibition by inorganic mercury. FEBS J. 2007 Apr;274(7):1849-61.
2 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
3 Prostaglandin E2 induces CYP1B1 expression via ligand-independent activation of the ERalpha pathway in human breast cancer cells. Toxicol Sci. 2010 Apr;114(2):204-16.
4 Aflatoxin B1 induces persistent epigenomic effects in primary human hepatocytes associated with hepatocellular carcinoma. Toxicology. 2016 Mar 28;350-352:31-9.
5 Effect of quercetin on paraoxonase 1 activity--studies in cultured cells, mice and humans. J Physiol Pharmacol. 2010 Feb;61(1):99-105.
6 Lead exposure is associated with decreased serum paraoxonase 1 (PON1) activity and genotypes. Environ Health Perspect. 2006 Aug;114(8):1233-6.
7 StJohn's wort extracts and some of their constituents potently inhibit ultimate carcinogen formation from benzo[a]pyrene-7,8-dihydrodiol by human CYP1A1. Cancer Res. 2003 Nov 15;63(22):8062-8.
8 Dietary polyphenols increase paraoxonase 1 gene expression by an aryl hydrocarbon receptor-dependent mechanism. Mol Cell Biol. 2004 Jun;24(12):5209-22.
9 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
10 Effects of some antibiotics on paraoxonase from human serum in vitro and from mouse serum and liver in vivo. Biol Pharm Bull. 2006 Aug;29(8):1559-63.
11 Induction of paraoxonase 1 and apolipoprotein A-I gene expression by aspirin. J Lipid Res. 2008 Oct;49(10):2142-8.
12 Effect of short term treatment with simvastatin and atorvastatin on lipids and paraoxonase activity in patients with hyperlipoproteinaemia. Curr Med Res Opin. 2004 Aug;20(8):1321-7.
13 Antioxidant effect of atorvastatin is independent of PON1 gene T(-107)C, Q192R and L55M polymorphisms in hypercholesterolaemic patients. Curr Med Res Opin. 2005 May;21(5):777-84.
14 Omics-based responses induced by bosentan in human hepatoma HepaRG cell cultures. Arch Toxicol. 2018 Jun;92(6):1939-1952.
15 Antiepileptic drugs: impacts on human serum paraoxonase-1. J Biochem Mol Toxicol. 2017 Jun;31(6).
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17 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
18 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
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20 The effect of fenofibrate on serum paraoxonase activity and inflammatory markers in patients with combined hyperlipidemia. Kardiol Pol. 2005 Jun;62(6):526-30.
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23 Atheroprotective effects of methotrexate on reverse cholesterol transport proteins and foam cell transformation in human THP-1 monocyte/macrophages. Arthritis Rheum. 2008 Dec;58(12):3675-83.
24 In vitro gene expression data supporting a DNA non-reactive genotoxic mechanism for ochratoxin A. Toxicol Appl Pharmacol. 2007 Apr 15;220(2):216-24.
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28 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
29 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
30 Esterase detoxication of acetylcholinesterase inhibitors using human liver samples in vitro. Toxicology. 2016 Apr 15;353-354:11-20.
31 Chemical synthesis of two series of nerve agent model compounds and their stereoselective interaction with human acetylcholinesterase and human butyrylcholinesterase. Chem Res Toxicol. 2009 Oct;22(10):1669-79.
32 Selenium supplementation restores the antioxidative capacity and prevents cell damage in bone marrow stromal cells in vitro. Stem Cells. 2006 May;24(5):1226-35.
33 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
34 Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s. Drug Metab Dispos. 2001 Jan;29(1):30-5.
35 Biocatalytic production of alpha-hydroxy ketones and vicinal diols by yeast and human aldo-keto reductases. Chem Biol Interact. 2013 Feb 25;202(1-3):195-203.
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38 A role for FXR and human FGF-19 in the repression of paraoxonase-1 gene expression by bile acids. J Lipid Res. 2006 Feb;47(2):384-92.

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