Biomaterial Database

The effect of phenobarbital and dexamethasone on hepatic cytochrome P-450 and alpha 1-acid glycoprotein in maternal and fetal guinea pigs. 1990

M D Hill, and F P Abramson

Department of Pharmacology, George Washington University Medical Center, Washington, DC 20037.

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.

UI	MeSH Term	Description	Entries
D007044	Hysterectomy	Excision of the uterus.	Hysterectomies
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D009961	Orosomucoid		Acid Seromucoid,Seromucoid,Serum Sialomucin,alpha 1-Acid Glycoprotein,alpha 1-Acid Seromucoid,A(1)-Acid Seromucoid,Acid alpha 1-Glycoprotein,Alpha(1)-Acid Glycoprotein,alpha 1-Acid Glycoprotein (Acute Phase),alpha 1-Glycoprotein Acid,Acid alpha 1 Glycoprotein,Glycoprotein, alpha 1-Acid,Seromucoid, Acid,Seromucoid, alpha 1-Acid,Sialomucin, Serum,alpha 1 Acid Glycoprotein,alpha 1 Acid Seromucoid,alpha 1 Glycoprotein Acid
D010634	Phenobarbital	A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations.	Phenemal,Phenobarbitone,Phenylbarbital,Gardenal,Hysteps,Luminal,Phenobarbital Sodium,Phenobarbital, Monosodium Salt,Phenylethylbarbituric Acid,Acid, Phenylethylbarbituric,Monosodium Salt Phenobarbital,Sodium, Phenobarbital
D011247	Pregnancy	The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.	Gestation,Pregnancies
D011433	Propranolol	A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs.	Dexpropranolol,AY-20694,Anaprilin,Anapriline,Avlocardyl,Betadren,Dociton,Inderal,Obsidan,Obzidan,Propanolol,Propranolol Hydrochloride,Rexigen,AY 20694,AY20694,Hydrochloride, Propranolol
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D001798	Blood Proteins	Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.	Blood Protein,Plasma Protein,Plasma Proteins,Serum Protein,Serum Proteins,Protein, Blood,Protein, Plasma,Protein, Serum,Proteins, Blood,Proteins, Plasma,Proteins, Serum
D003577	Cytochrome P-450 Enzyme System	A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.	Cytochrome P-450,Cytochrome P-450 Enzyme,Cytochrome P-450-Dependent Monooxygenase,P-450 Enzyme,P450 Enzyme,CYP450 Family,CYP450 Superfamily,Cytochrome P-450 Enzymes,Cytochrome P-450 Families,Cytochrome P-450 Monooxygenase,Cytochrome P-450 Oxygenase,Cytochrome P-450 Superfamily,Cytochrome P450,Cytochrome P450 Superfamily,Cytochrome p450 Families,P-450 Enzymes,P450 Enzymes,Cytochrome P 450,Cytochrome P 450 Dependent Monooxygenase,Cytochrome P 450 Enzyme,Cytochrome P 450 Enzyme System,Cytochrome P 450 Enzymes,Cytochrome P 450 Families,Cytochrome P 450 Monooxygenase,Cytochrome P 450 Oxygenase,Cytochrome P 450 Superfamily,Enzyme, Cytochrome P-450,Enzyme, P-450,Enzyme, P450,Enzymes, Cytochrome P-450,Enzymes, P-450,Enzymes, P450,Monooxygenase, Cytochrome P-450,Monooxygenase, Cytochrome P-450-Dependent,P 450 Enzyme,P 450 Enzymes,P-450 Enzyme, Cytochrome,P-450 Enzymes, Cytochrome,Superfamily, CYP450,Superfamily, Cytochrome P-450,Superfamily, Cytochrome P450
D003640	Dealkylation	The removing of alkyl groups from a compound. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)	Dealkylations