| Alteration of the Expression of Pesticide-Metabolizing Enzymes in Pregnant Mice: Potential Role in the Increased Vulnerability of the Developing Brain. | |
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MedLine Citation:
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PMID: 23223497 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. Here, 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 to virgin mice, alterations in the expression occurred at multiple time-points, with the largest changes observed on GD 14. At this timepoint, 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. |
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Authors:
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Marie C Fortin; Lauren M Aleksunes; Jason R Richardson |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-12-4 |
Journal Detail:
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Title: Drug metabolism and disposition: the biological fate of chemicals Volume: - ISSN: 1521-009X ISO Abbreviation: Drug Metab. Dispos. Publication Date: 2012 Dec |
Date Detail:
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Created Date: 2012-12-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9421550 Medline TA: Drug Metab Dispos Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1 Environmental and Occupational Health Sciences Institute; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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