The effect of phenobarbital and dexamethasone on hepatic cytochrome P-450 and alpha 1-acid glycoprotein in maternal and fetal guinea pigs.
The effects of phenobarbital (PB) and dexamethasone (DX) on maternal and fetal hepatic cytochrome P450 content, benzphetamine (BzP) demethylation activity, the plasma concentration of alpha 1-acid glycoprotein (AGP), and the binding of propranolol (PPL) were examined in guinea pigs. In maternal guinea pigs, PB increased AGP-specific PPL binding by 131%, P450 by 94%, and BzP demethylation by 261%. DX only increased maternal AGP-specific PPL binding (122%). In fetal guinea pigs, neither PB nor DX resulted in significant increase for any of these parameters. The combination of PB and DX synergistically increased fetal P450 content (153% increase) and BzP demethylation (84% increase). In contrast, this combination treatment did not increase maternal P450 and BzP demethylation to a greater extent than by PB treatment alone nor did it increase the binding of PPL in PCA-treated fetal plasma. The synergy of P450 induction found in the fetus implicates glucocorticoids as important regulators of fetal hepatic microsomal enzyme maturation.
Hill
M D
MD
Department of Pharmacology, George Washington University Medical Center, Washington, DC 20037.
Abramson
F P
FP
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003640:Dealkylation; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000378:metabolism*; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D007044:Hysterectomy; D008099:Liver / Q000201:enzymology*; D009961:Orosomucoid / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology*; D011247:Pregnancy; D011433:Propranolol / Q000097:blood; D011485:Protein Binding / Q000187:drug effects
D001798:Blood Proteins; D009961:Orosomucoid; D001564:Benzo(a)pyrene; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; D011433:Propranolol; D010634:Phenobarbital