Document Detail


Alteration of the expression of pesticide-metabolizing enzymes in pregnant mice: potential role in the increased vulnerability of the developing brain.
MedLine Citation:
PMID:  23223497     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Studies on therapeutic drug disposition in humans have shown significant alterations as the result of pregnancy. However, it is not known whether pesticide metabolic capacity changes throughout pregnancy, which could affect exposure of the developing brain. We sought to determine the effect of pregnancy on the expression of hepatic enzymes involved in the metabolism of pesticides. Livers were collected from virgin and pregnant C57BL/6 mice at gestational days (GD)7, GD11, GD14, GD17, and postpartum days (PD)1, PD15, and PD30. Relative mRNA expression of several enzymes involved in the metabolism of pesticides, including hepatic cytochromes (Cyp) P450s, carboxylesterases (Ces), and paraoxonase 1 (Pon1), were assessed in mice during gestation and the postpartum period. Compared with virgin mice, alterations in the expression occurred at multiple time points, with the largest changes observed on GD14. At this time point, the expression of most of the Cyps involved in pesticide metabolism in the liver (Cyp1a2, Cyp2d22, Cyp2c37, Cyp2c50, Cyp2c54, and Cyp3a11) were downregulated by 30% or more. Expression of various Ces isoforms and Pon1 were also decreased along with Pon1 activity. These data demonstrate significant alterations in the expression of key enzymes that detoxify pesticides during pregnancy, which could alter exposure of developing animals to these chemicals.
Authors:
Marie C Fortin; Lauren M Aleksunes; Jason R Richardson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-12-04
Journal Detail:
Title:  Drug metabolism and disposition: the biological fate of chemicals     Volume:  41     ISSN:  1521-009X     ISO Abbreviation:  Drug Metab. Dispos.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-18     Completed Date:  2013-07-12     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  9421550     Medline TA:  Drug Metab Dispos     Country:  United States    
Other Details:
Languages:  eng     Pagination:  326-31     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Aryldialkylphosphatase / genetics,  metabolism*
Biotransformation
Brain / drug effects,  embryology
Carboxylesterase / genetics,  metabolism*
Cytochrome P-450 Enzyme System / genetics,  metabolism*
Female
Gene Expression Regulation, Enzymologic
Gestational Age
Isoenzymes
Liver / enzymology*
Mice
Mice, Inbred C57BL
Neurotoxicity Syndromes / embryology,  etiology
Pesticides / metabolism*,  toxicity
Pregnancy
RNA, Messenger / metabolism
Receptors, Cytoplasmic and Nuclear / genetics,  metabolism
Substrate Specificity
Transcription Factors / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
DK080774/DK/NIDDK NIH HHS; ES005022/ES/NIEHS NIH HHS; ES007148/ES/NIEHS NIH HHS; ES015991/ES/NIEHS NIH HHS; ES020522/ES/NIEHS NIH HHS; R00 DK080774/DK/NIDDK NIH HHS; R01 ES020522/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Isoenzymes; 0/Pesticides; 0/RNA, Messenger; 0/Receptors, Cytoplasmic and Nuclear; 0/Transcription Factors; 9035-51-2/Cytochrome P-450 Enzyme System; EC 3.1.1.1/Carboxylesterase; EC 3.1.8.1/Aryldialkylphosphatase; EC 3.1.8.1/PON1 protein, mouse
Comments/Corrections
Comment In:
Drug Metab Dispos. 2013 Feb;41(2):256-62   [PMID:  23328895 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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