Document Detail


2,3,7,8-Tetrachlorodibenzo-p-dioxin treatment alters eicosanoid levels in several organs of the mouse in an aryl hydrocarbon receptor-dependent fashion.
MedLine Citation:
PMID:  22230337     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) adversely affects many mammalian organs and tissues. These effects are mediated by the aryl hydrocarbon receptor (AHR). CYP1A1, CYP1A2 and CYP1B1 are upregulated by the liganded AHR. These (and other) cytochromes P450 can metabolize arachidonic acid into a variety of bioactive eicosanoids. Towards investigating a potential role of eicosanoids in TCDD toxicity, arachidonic acid, two other unsaturated long-chain fatty acids, and up to twenty-five eicosanoids were measured in five organs/tissues of male and female wild-type and Ahr null mice treated or untreated with TCDD. TCDD generally increased the levels of the four dihydroxyeicosatrienoic acids (DHETs) and (where measured) 5,6-epoxyeicosatrienoic acid and 18-, 19- and 20-hydroxyeicosatrienoic acids (HETEs) in the serum, liver, spleen and lungs, but not the heart, of both sexes, and increased the levels in the serum, liver and spleen of several metabolites that are usually considered products of lipoxygenase activity, but which may also be generated by cytochromes P450. TCDD also increased the levels of the esterified forms of these eicosanoids in the liver in parallel with the corresponding free forms. The levels of prostanoids were generally not affected by TCDD. The above changes did not occur in Ahr null mice, and are therefore mediated by the AHR. TCDD increased the mRNA levels of Cyp1a1, Cyp1a2, Cyp1b1 and the Pla2g12a form of phospholipase A(2) to varying degrees in the different organs, and these increases correlated with some but not all the changes in eicosanoids levels in the organs, suggesting that other enzymes may also be involved.
Authors:
Peter Bui; Parrisa Solaimani; Xiaomeng Wu; Oliver Hankinson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-12-20
Journal Detail:
Title:  Toxicology and applied pharmacology     Volume:  259     ISSN:  1096-0333     ISO Abbreviation:  Toxicol. Appl. Pharmacol.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-02-27     Completed Date:  2012-06-28     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  0416575     Medline TA:  Toxicol Appl Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  143-51     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
Affiliation:
Molecular Toxicology Program, University of California, Los Angeles, California 90095, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cytochrome P-450 Enzyme System / genetics,  metabolism*
Eicosanoids / blood,  metabolism*
Environmental Pollutants / toxicity*
Female
Heart / drug effects
Liver / drug effects,  metabolism
Lung / drug effects,  metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Myocardium / metabolism
RNA / chemistry,  genetics
Real-Time Polymerase Chain Reaction
Receptors, Aryl Hydrocarbon / metabolism*
Specific Pathogen-Free Organisms
Spleen / drug effects,  metabolism
Tandem Mass Spectrometry
Tetrachlorodibenzodioxin / analogs & derivatives*,  toxicity
Grant Support
ID/Acronym/Agency:
R01 CA028868-22/CA/NCI NIH HHS; R01 CA028868-23/CA/NCI NIH HHS; R01 CA028868-24/CA/NCI NIH HHS; R01 ES015384-04S1/ES/NIEHS NIH HHS; R01 ES015384-05/ES/NIEHS NIH HHS; R01CA28868/CA/NCI NIH HHS; R01ES015384/ES/NIEHS NIH HHS; T32 ES015457-02/ES/NIEHS NIH HHS; T32 ES015457-03/ES/NIEHS NIH HHS; T32 ES015457-04/ES/NIEHS NIH HHS; T32-GM0843/GM/NIGMS NIH HHS; T32ES015457/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Eicosanoids; 0/Environmental Pollutants; 0/Receptors, Aryl Hydrocarbon; 1746-01-6/Tetrachlorodibenzodioxin; 61CLS478M1/1,2,7,8-tetrachlorodibenzo-p-dioxin; 63231-63-0/RNA; 9035-51-2/Cytochrome P-450 Enzyme System
Comments/Corrections

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