Biomaterial Database

Induction of liver cytochrome P4502E1 by pyrazole and 4-methylpyrazole in neonatal rats. 1993

D Wu, and A I Cederbaum

Department of Biochemistry, Mount Sinai School of Medicine, New York, New York.

Cytochrome P4502E1 (P4502E1) is not present in fetal rat liver; activation of the gene occurs within hours after birth. In adult rats, chemical inducers increase P4502E1 levels largely by a post-transcriptional type of mechanism. Experiments were carried out to evaluate how soon after birth chemicals such as pyrazole or 4-methylpyrazole (MP) can induce P4502E1 and whether the mechanism for induction at these early developmental stages, during active transcription, is different from that found in adults. No P4502E1 was found in fetal liver; in liver microsomes from saline control rats, there was a progressive increase in P4502E1 levels and oxidation of dimethylnitrosamine every 2 days after birth, with maximal levels 8 to 14 days after birth. Injecting pyrazole and MP on day 0 and day 1 after birth, resulted in 2- to 4-fold increases (compared to saline control values) in P4502E1 content and oxidation of dimethylnitrosamine in liver microsomes isolated from 2-day-old pups. This extent of increase by treatment with pyrazole or MP over saline control values was similar to that found when pups were treated for 2 days with the inducers on days 2, 4, 6, 8, 12 and 19 after birth. Northern blot analysis indicated a progressive increase in P4502E1 mRNA levels, reaching a maximum at about 8 days after birth for saline-treated pups. Pyrazole or MP did not increase P4502E1 mRNA levels over values for the saline controls.(ABSTRACT TRUNCATED AT 250 WORDS)

UI	MeSH Term	Description	Entries
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
D010084	Oxidation-Reduction	A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).	Redox,Oxidation Reduction
D010089	Oxidoreductases, N-Demethylating		N-Demethylase,N-Demethylases,Oxidoreductases, N Demethylating,Demethylating Oxidoreductases, N,N Demethylase,N Demethylases,N Demethylating Oxidoreductases,N-Demethylating Oxidoreductases
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
D011720	Pyrazoles	Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.
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
D004128	Dimethylnitrosamine	A nitrosamine derivative with alkylating, carcinogenic, and mutagenic properties. It causes serious liver damage and is a hepatocarcinogen in rodents.	Nitrosodimethylamine,N-Nitrosodimethylamine,NDMA Nitrosodimethylamine,N Nitrosodimethylamine,Nitrosodimethylamine, NDMA
D004790	Enzyme Induction	An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.	Induction, Enzyme
D005260	Female		Females
D000077604	Fomepizole	A pyrazole and competitive inhibitor of ALCOHOL DEHYDROGENASE that is used for the treatment of poisoning by ETHYLENE GLYCOL or METHANOL.	4-Methylpyrazole,4-Methylpyrazole Monohydrochloride,Antizol,4 Methylpyrazole,4 Methylpyrazole Monohydrochloride