| Altered cytochrome P450 expression in mice during pregnancy. | |
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MedLine Citation:
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PMID: 20971892 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Human pregnancy is known to influence hepatic drug metabolism in a cytochrome (P450)-specific manner. However, the underlying mechanisms remain unknown, in part due to a lack of experimental models to study altered drug metabolism during pregnancy. In this study, we examined how pregnancy influences expression of major P450 isoforms in mice. Liver tissues were isolated from female FVB/N-mice at different gestational time points: prepregnancy, 7, 14, and 21 days of pregnancy, and 7 days postpartum. mRNA expression levels of major P450 isoforms (Cyp1a2, Cyp2a5, Cyp2b10, Cyp2c37, Cyp2d22, Cyp2e1, Cyp3a11, and Cyp3a41) in the liver tissues were determined by quantitative real-time polymerase chain reaction. Whereas Cyp2a5 expression was unchanged, Cyp3a41 expression was significantly increased during pregnancy. In contrast, expression of Cyp1a2, Cyp2c37, Cyp2d22, Cyp2e1, and Cyp3a11 was decreased. Expression of Cyp2d22 and Cyp2e1 isoforms correlated with that of peroxisome proliferator-activated receptor (PPAR)α in the mouse livers, suggesting potential involvement of PPARα in down-regulation of the P450 expression during pregnancy. Effects of pregnancy on expression of other P450 mouse isoforms as well as on in vivo drug disposition remain to be characterized. These results provide a guide for future studies on P450 regulation during pregnancy. |
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Authors:
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Kwi Hye Koh; Hui Xie; Ai-Ming Yu; Hyunyoung Jeong |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-10-22 |
Journal Detail:
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Title: Drug metabolism and disposition: the biological fate of chemicals Volume: 39 ISSN: 1521-009X ISO Abbreviation: Drug Metab. Dispos. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-19 Completed Date: 2011-04-28 Revised Date: 2012-02-01 |
Medline Journal Info:
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Nlm Unique ID: 9421550 Medline TA: Drug Metab Dispos Country: United States |
Other Details:
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Languages: eng Pagination: 165-9 Citation Subset: IM |
Affiliation:
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Department of Biopharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, USA. yjeong@uic.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cytochrome P-450 Enzyme System / genetics* Cytokines / genetics Female Gene Expression Regulation, Enzymologic* Gestational Age Isoenzymes Liver / enzymology*, immunology Mice Mice, Inbred Strains Pregnancy / immunology, metabolism* RNA, Messenger / genetics Reverse Transcriptase Polymerase Chain Reaction Transcription Factors / genetics Up-Regulation |
| Grant Support | |
ID/Acronym/Agency:
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HD055313/HD/NICHD NIH HHS; K12 HD055892-04/HD/NICHD NIH HHS; K12-HD055892/HD/NICHD NIH HHS; UL1-RR029879/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/Isoenzymes; 0/RNA, Messenger; 0/Transcription Factors; 9035-51-2/Cytochrome P-450 Enzyme System |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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