Biomaterial Database

Cytochrome P450 induction and metabolism of alkoxyresorufins, ethylmorphine and testosterone in cultured hepatocytes from goats, sheep and cattle. 1993

G A van 't Klooster, and B J Blaauboer, and J Noordhoek, and A S van Miert

Department of Veterinary Pharmacology and Toxicology, University of Utrecht, The Netherlands.

Very little is known of cytochrome P450 (P450) patterns and enzyme characteristics in food-producing animal species. Oxidative metabolism of alkoxyresorufins, ethylmorphine (EtM) and testosterone (TST) was used to monitor the effects of the P450 inducers phenobarbital (PB), beta-naphthoflavone (BNF), dexamethasone (DEX) and triacetyloleandomycin (TAO) in primary cultured hepatocytes from goats, sheep and cattle. BNF effectively and specifically induced ethoxyresorufin deethylase (> 20-fold), indicating the presence of an inducible P450 1A form, and down-regulated EtM demethylation and most selected TST hydroxylations. In non-induced hepatocyte cultures, TST was metabolized to 6 beta-, 2 beta-, 12 beta-, and 11 alpha-hydroxy-TST (OHT). PB and, to a lesser extent, DEX non-specifically induced all OHT formations, and EtM demethylation. TAO almost completely inhibited OHT formation and EtM demethylation. These results indicate the involvement of principally one P450 form, or a restricted number of related P450 forms, presumably belonging to the P450 3A subfamily. In western blot analysis, cross reactivity was found with rat anti-P450 3A1 and anti-sheep P450 3A. A more specific PB effect was observed for 16 alpha-OHT, which may be formed though a ruminant P450 2B form. None of the inducers influenced pentoxyresorufin depentylase (PROD) or EtM O-deethylation. Metabolite patterns and inducibility of selected activities in ruminant hepatocytes are in accordance with previous findings in goats in vivo. Cytochrome P450 characteristics in ruminants appear to differ from those in rats whereas similarities to the situation in humans appear to exist.

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
D008297	Male		Males
D010078	Oxazines	Six-membered heterocycles containing an oxygen and a nitrogen.
D010088	Oxidoreductases	The class of all enzymes catalyzing oxidoreduction reactions. The substrate that is oxidized is regarded as a hydrogen donor. The systematic name is based on donor:acceptor oxidoreductase. The recommended name will be dehydrogenase, wherever this is possible; as an alternative, reductase can be used. Oxidase is only used in cases where O2 is the acceptor. (Enzyme Nomenclature, 1992, p9)	Dehydrogenases,Oxidases,Oxidoreductase,Reductases,Dehydrogenase,Oxidase,Reductase
D002417	Cattle	Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.	Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
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
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
D005036	Ethylmorphine	A narcotic analgesic and antitussive. It is metabolized in the liver by ETHYLMORPHINE-N-DEMETHYLASE and used as an indicator of liver function.	Ethomorphine,Dionine,Ethylmorphine Hydrochloride, (5alpha,6alpha)-Isomer,Ethylmorphine Hydrochloride, Dihydrate, (5alpha,6alpha)-Isomer,Ethylmorphine Sulfate (2:1), (5alpha,6alpha)-Isomer,Ethylmorphine, (5alpha,6beta)-Isomer,Trachyl
D005260	Female		Females