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Effects of valproate on xenobiotic biotransformation in rat liver. In vivo and in vitro experiments.

Rogiers, V; Callaerts, A; Vercruysse, A; Akrawi, M; Shephard, E; Phillips, I; (1992) Effects of valproate on xenobiotic biotransformation in rat liver. In vivo and in vitro experiments. Pharm Weekbl Sci , 14 (3A) pp. 127-131.

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Abstract

Male Wistar rats were in vivo exposed for 2 weeks to 100 micrograms/ml sodium valproate by subcutaneous implantation of osmotic pumps and hepatocytes were isolated. As an in vitro model co-cultures of rat hepatocytes with epithelial cells were daily treated with valproate (25, 50, 100, 200 micrograms/ml) for 2 weeks. In both models the cytochrome P-450 content and the enzymatic activities of 7-ethoxycoumarin O-deethylase, aldrin epoxidase and glutathione S-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-ethoxycoumarin O-deethylase activity increased significantly after valproate treatment. On the other hand, the activities of aldrin epoxidase and glutathione S-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 pronounced in vitro than in vivo.

Type: Article
Title: Effects of valproate on xenobiotic biotransformation in rat liver. In vivo and in vitro experiments.
Location: Netherlands
Keywords: 7-Alkoxycoumarin O-Dealkylase, Animals, Biotransformation, Cells, Cultured, Cytochrome P-450 Enzyme System, Glutathione Transferase, Liver, Male, Mixed Function Oxygenases, RNA, Messenger, Rats, Rats, Inbred Strains, Valproic Acid, Xenobiotics
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: http://discovery.ucl.ac.uk/id/eprint/1414300
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