Applicability of cultured hepatocytes derived from goat, sheep and cattle in comparative drug metabolism studies. 1994

G A van 't Klooster, and F M Woutersen-van Nijnanten, and B J Blaauboer, and J Noordhoek, and A S van Miert
Department of Veterinary Basic Sciences, University of Utrecht, The Netherlands.

1. Using trimethoprim (TMP), scoparone (SCOP), ethylmorphine (EtM), 1-naphthol (1-N) and phenol red (PhR) as test substrates, biotransformation activities were investigated in cultured hepatocytes from male and female rat, male and female goat, and female sheep and cattle. 2. As compared with rat hepatocytes, the total culture cytochrome P450 content was relatively well maintained in ruminant hepatocytes. In 72 h, it decreased to approximately half the initial content, whereas in rat hepatocytes only 30% was maintained. In ruminant hepatocytes, sulphation of 1-N remained fairly stable, glucuronidation of PhR decreased gradually, and glucuronidation of 1-N increased during the 72-h culture period. 3. Oxidative metabolism of TMP was rapid in goat and sheep hepatocytes, as compared with rat hepatocytes, reflecting species differences in TMP pharmacokinetics in vivo. In contrast with rat hepatocytes, 6-O-demethylation was by far the major pathway of scoparone metabolism in ruminant hepatocytes. The glucuronidation and sulphation activities were similar among the species. 4. In goat liver cells, sex differences in some oxidative biotransformations were observed, females being more active than males. In rat hepatocytes, a reverse sex difference was observed. 5. In conclusion, cultured hepatocytes from agricultural target species appear a useful in vitro model to study comparative metabolism of veterinary drugs and other xenobiotics. Comparing rat and ruminant, sex and species differences and similarities in drug metabolism can be observed that reflect the in vivo situation.

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
D009284 Naphthols Naphthalene derivatives carrying one or more hydroxyl (-OH) groups at any ring position. They are often used in dyes and pigments, as antioxidants for rubber, fats, and oils, as insecticides, in pharmaceuticals, and in numerous other applications. Hydroxynaphthalene,Hydroxynaphthalenes,Naphthol
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
D010637 Phenolsulfonphthalein Red dye, pH indicator, and diagnostic aid for determination of renal function. It is used also for studies of the gastrointestinal and other systems. Phenol Red,Sulfonphthal,Sulphental,Sulphonthal
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
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
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
D003374 Coumarins Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid. 1,2-Benzopyrone Derivatives,1,2-Benzopyrones,Coumarin Derivative,Coumarine,1,2-Benzo-Pyrones,Benzopyran-2-ones,Coumarin Derivatives,Coumarines,1,2 Benzo Pyrones,1,2 Benzopyrone Derivatives,1,2 Benzopyrones,Benzopyran 2 ones,Derivative, Coumarin,Derivatives, 1,2-Benzopyrone,Derivatives, Coumarin
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

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