Comparison of the effects of phenobarbital and its hydroxylated metabolites on drug-metabolizing enzymes during ontogenesis.
Twenty-two-day-old fetal and five-day-old newborn rats were pretreated with phenobarbital and its hydroxylated metabolites. Drug-metabolizing enzymes (cytochrome P450, epoxide hydrolase, UDP-glucuronosyltransferase, and glutathione-S-transferase) and microsomal ribonuclease were not modified in fetuses treated with 80 or 400 mg . kg-1 of p-hydroxyphenobarbital, in spite of its accumulation in fetal liver. At fetal age, phenobarbital was a poor inducer of drug-metabolizing enzymes. In five-day-old newborns, p-hydroxyphenobarbital provoked a proliferation of endoplasmic reticulum without enzyme induction, whereas phenobarbital induced some drug-metabolizing enzymes. Thus, the effects of p-hydroxyphenobarbital and phenobarbital are retained in five-day-old rats, but undetectable in the fetuses.
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001463:Barbiturates / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004851:Epoxide Hydrolases / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D008099:Liver / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains
D001463:Barbiturates; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases; D010634:Phenobarbital