Comparative effects of drugs on P-glycoprotein expression and activity using rat and human trophoblast models.
The drug efflux transporter P-glycoprotein (P-gp) is an active component of the placental barrier which protects the fetus against maternal xenobiotics. The goal of the study was to compare species difference between human and rat in terms of susceptibility to drugs at the level of the placental barrier using in vitro models in order to improve translation from rat to human. Effects of selected drugs (Aspirin, Methadone, a Cardiovascular Proprietary Compound, Thalidomide) on cytotoxicity and P-gp expression and activity were compared using human and rat trophoblast cultures. No direct cytotoxicity of drugs on trophoblasts was noted in both invitro models, but for Thalidomide a proliferative effect on human trophoblast primocultures was observed. All tested drugs induced changes towards P-gp; for each drug the same profile was noted in both human and rat trophoblast models except for Thalidomide. Observation of this similar response between these two in vitro trophoblast models is promising for assessment between P-gp expression and activity of drugs towards placental function.
Beghin
D
D
Univ Paris-Sud, EA 2706, Faculté de Pharmacie, Châtenay-Malabry, France. delphinebeghin@free.fr
Delongeas
J-L
JL
Claude
N
N
Farinotti
R
R
Forestier
F
F
Gil
S
S
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000633:toxicity*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008691:Methadone / Q000008:administration & dosage / Q000633:toxicity*; D010920:Placenta / Q000166:cytology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013792:Thalidomide / Q000008:administration & dosage / Q000633:toxicity*; D013997:Time Factors; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D013792:Thalidomide; D001241:Aspirin; D008691:Methadone