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Updated: Jun 10, 2026

Mass Spectrometry and Luminogenic-based Approaches to Characterize Phase I Metabolic Competency of In Vitro Cell Cultures
Published on: March 28, 2017
Studies on the mechanism of coumarin-induced toxicity in rat hepatocytes
C den Besten1, S A Körösi, J A Beamand
1Department of Toxicology, Wageningen Agricultural University, 6700 EV Wageningen, The Netherlands.
Abstract:
Rat hepatocyte suspensions have been used as a model system for some studies on the mechanism of coumarin-induced hepatotoxicity. Hepatocytes were isolated from male Sprague-Dawley rats and subjected to Percoll centrifugation to obtain preparations with >/=92% viability. Coumarin produced time- and concentration-dependent cytotoxic effects in rat hepatocytes as indicated by loss of cell viability and glutathione depletion. [3-(14)C]Coumarin was metabolized by rat hepatocytes to polar metabolites including o-hydroxyphenylacetic acid and to metabolites that became covalently bound to hepatocyte proteins. The addition of 10 mum-ellipticine significantly reduced coumarin cytotoxicity, coumarin metabolism and covalent binding in rat hepatocytes. These results demonstrate that coumarin-induced liver injury in the rat can be modelled in hepatocyte suspensions and that toxicity appears to be due to one or more cytochrome P-450 generated metabolites.
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