caa a22 4500 469026308 CHVBK 20180323132730.0 cr unu---uuuuu 170328e19920601xx s 000 0 eng 10.1007/BF01962703 doi (NATIONALLICENCE)springer-10.1007/BF01962703 Effects of valproate on xenobiotic biotransformation in rat liver [Elektronische Daten] In vivo and in vitro experiments [V. Rogiers, A. Callaerts, A. Vercruysse, M. Akrawi, E. Shephard, I. Phillips] Male Wistar rats werein vivo exposed for 2 weeks to 100 μg/ml sodium valproate by subcutaneous implantation of osmotic pumps and hepatocytes were isolated. As anin vitro model co-cultures of rat hepatocytes with epithelial cells were daily treated with valproate (25, 50, 100, 200μg/ml) for 2 weeks. In both models the cytochrome P-450 content and the enzymatic activities of 7-ethoxycoumarinO-deethylase, aldrin epoxidase and glutathioneS-transferase were determined in valproate-treated hepatocytes, in controls and in phenobarbital-induced cells. It appeared that in both systems the cytochrome P-450 content and the 7-ethoxycoumarinO-deethylase activity increased significantly after valproate treatment. On the other hand, the activities of aldrin epoxidase and glutathioneS-transferase decreased. A cDNA probe, encoding rat P450IIB2 was used to determine whether mRNAs encoding the P450IIB subfamily were induced by valproate. It became clear that the inducing effect of valproate was even more pronouncedin vitro thanin vivo. Royal Dutch Association for Advancement of Pharmacy, 1992 Aldrin epoxidase nationallicence 7-Alkoxycoumarin O -dealkylase nationallicence Biotransformation nationallicence Cytochrome P-450 nationallicence Enzyme induction nationallicence Glutathione transferases nationallicence Hepatocytes nationallicence Valproic acid nationallicence Rogiers V. Department of Toxicology, Free University Brussels, Laarbeeklaan 103, 1090, Brussels, Belgium aut Callaerts A. Department of Toxicology, Free University Brussels, Laarbeeklaan 103, 1090, Brussels, Belgium aut Vercruysse A. Department of Toxicology, Free University Brussels, Laarbeeklaan 103, 1090, Brussels, Belgium aut Akrawi M. Department of Biochemistry and Molecular Biology, University College London, Gower Street, WC1E 6BT, London, UK aut Shephard E. Department of Biochemistry and Molecular Biology, University College London, Gower Street, WC1E 6BT, London, UK aut Phillips I. Department of Biochemistry, Queen Mary and Westfield College, University of London, Mile End Road, E1 4NS, London, UK aut Pharmaceutisch Weekblad Kluwer Academic Publishers 14/3(1992-06-01), 127-131 0031-6911 14:3<127 1992 14 11096 https://doi.org/10.1007/BF01962703 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF01962703 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Rogiers V. Department of Toxicology, Free University Brussels, Laarbeeklaan 103, 1090, Brussels, Belgium aut NATIONALLICENCE 700 1- Callaerts A. Department of Toxicology, Free University Brussels, Laarbeeklaan 103, 1090, Brussels, Belgium aut NATIONALLICENCE 700 1- Vercruysse A. Department of Toxicology, Free University Brussels, Laarbeeklaan 103, 1090, Brussels, Belgium aut NATIONALLICENCE 700 1- Akrawi M. Department of Biochemistry and Molecular Biology, University College London, Gower Street, WC1E 6BT, London, UK aut NATIONALLICENCE 700 1- Shephard E. Department of Biochemistry and Molecular Biology, University College London, Gower Street, WC1E 6BT, London, UK aut NATIONALLICENCE 700 1- Phillips I. Department of Biochemistry, Queen Mary and Westfield College, University of London, Mile End Road, E1 4NS, London, UK aut NATIONALLICENCE 773 0- Pharmaceutisch Weekblad Kluwer Academic Publishers 14/3(1992-06-01), 127-131 0031-6911 14:3<127 1992 14 11096 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer