Induction of hepatic CYP2B in foetal and neonatal rats after maternal administration of phenobarbital.
We examined hepatic cytochrome P450 (CYP) induction in rat foetuses and neonates by phenobarbital administered through placenta or breast feeding. In an intraperitoneal study, phenobarbital was administered intraperitoneally to mother rats once a day for 7 consecutive days before delivery. The livers were removed from foetuses, neonates, and mothers just before and 5 and 10 days after delivery. In oral administration study, water containing phenobarbital was given orally ad libitum from day 13 of pregnancy to 3 weeks after delivery (end of lactation). The livers were removed from neonates and mothers just before and one week after delactation. Phenobarbital administered intraperitoneally increased both the activity and the protein expression of CYP2B in 5-day-old neonates, even though the administration ended before delivery. This increase had disappeared in 10-day-old neonates. In mother rats, phenobarbital increased CYP2B just before and 5 days after delivery, while no increase was detected 10 days after delivery. Phenobarbital administered orally also increased both the activity and the protein expression of CYP2B of neonates and mothers during lactation and this increase also disappeared 1 week after delactation. Neither activity nor protein expression of CYP3A were induced in perinates at any age examined in either administration route. In mother rats, increase in CYP3A was found only just before delivery in the peritoneal administration study. Our results suggest that phenobarbital administered through placenta or breast milk transiently induces hepatic CYP2B in newborn rats but that the influence of phenobarbital does not last long.
Asoh
M
M
Department of Pharmacology, St. Marianna University School of Medicine, Kanagawa, Japan.
Tateishi
T
T
Kumai
T
T
Kobayashi
S
S
D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D001189:Aryl Hydrocarbon Hydroxylases; D019362:Cytochrome P-450 CYP2B1 / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects*; D005260:Female; D007274:Injections, Intraperitoneal; D007774:Lactation; D008099:Liver / Q000201:enzymology*; D008431:Maternal-Fetal Exchange; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013250:Steroid Hydroxylases / Q000378:metabolism