Document Detail


Development and characterisation of a new model of rat trophoblasts.
MedLine Citation:
PMID:  19013229     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The placenta plays a key role during pregnancy. In vitro models have proven to assess the role of placental transporters in the exchange of nutrients, waste products and the distribution of drugs between the maternal and fetal compartments. Therefore, a primoculture of Wistar rat trophoblasts from the labyrinth zone was developed and characterised. Expression of placental transporters including P-glycoprotein (P-gp) and bcrp was evaluated by western blot and their activity using different inhibitors. A time-dependent increase in P-gp expression was noted from primocultures Day 2 to Day 4 followed by a plateau thereafter, whereas bcrp expression was stable throughout the culture period. P-gp and bcrp expression was maintained after seven passages in primocultures and in cryopreserved trophoblasts (up to 3 freezings and 10 passages). Activity of efflux transporters was confirmed in both placental primocultures and cryopreserved trophoblasts by an approximately 60% inhibition with cyclosporin A and valspodar for P-gp and 55% with elacridar for bcrp. In sum, this new in vitro model seems promising for a better understanding of the role of P-gp and bcrp in the toxicity of drugs during pregnancy and could be considered as an additional step towards the minimization of animal testing during drug development.
Authors:
D Beghin; J-L Delongeas; N Claude; F Forestier; R Farinotti; S Gil
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-10-25
Journal Detail:
Title:  Toxicology in vitro : an international journal published in association with BIBRA     Volume:  23     ISSN:  0887-2333     ISO Abbreviation:  Toxicol In Vitro     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-01-12     Completed Date:  2009-03-24     Revised Date:  2009-04-10    
Medline Journal Info:
Nlm Unique ID:  8712158     Medline TA:  Toxicol In Vitro     Country:  England    
Other Details:
Languages:  eng     Pagination:  141-7     Citation Subset:  IM    
Affiliation:
Univ Paris-Sud, EA 2706, IFR141, Faculté de Pharmacie, 92296 Chatenay-Malabry Cedex, France. delphinebeghin@free.fr
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MeSH Terms
Descriptor/Qualifier:
ATP-Binding Cassette Transporters / antagonists & inhibitors,  metabolism
Animal Testing Alternatives*
Animals
Cell Proliferation
Cell Survival / physiology
Cryopreservation
Cyclosporine / pharmacology
Cyclosporins / pharmacology
Drug Evaluation, Preclinical / methods*
Female
Fluoresceins / metabolism
Fluorescent Dyes / metabolism
Neoplasm Proteins / antagonists & inhibitors,  metabolism
Organ Culture Techniques / methods*
P-Glycoprotein / antagonists & inhibitors,  metabolism
Pregnancy
Rats
Rats, Wistar
Rhodamine 123 / metabolism
Trophoblasts / cytology,  drug effects,  metabolism*
Chemical
Reg. No./Substance:
0/ABCG2 protein, human; 0/ATP-Binding Cassette Transporters; 0/Cyclosporins; 0/Fluoresceins; 0/Fluorescent Dyes; 0/Neoplasm Proteins; 0/P-Glycoprotein; 121584-18-7/valspodar; 148504-34-1/calcein AM; 59865-13-3/Cyclosporine; 62669-70-9/Rhodamine 123

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


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