Stability of Phase II Conjugation Systems in Cultured Precision-cut Rat Hepatic Slices.
The aim of the present study was to investigate the stability of Phase II conjugation enzymes in precision-cut rat liver slices that have been cultured, using the multiwell plate system, for various periods of time up to 72 hours. The enzyme activities monitored were epoxide hydrolase, glutathione S-transferase and the associated glutathione reductase, sulfotransferase and glucuronyl transferase. The activity of all enzymes studied declined with time when expressed per slice, but the rate of loss differed among the various enzymes. However, in most cases substantial Phase II activity was still present in the liver slices following a 24-hour incubation, and in some cases significant activity was even retained in slices cultured for 72 hours. These studies indicate that precision-cut liver slices maintain Phase II activity for long periods of time, thus allowing metabolic studies involving prolonged incubations to be performed.
Hashemi
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Drug Development, Hoechst Marion Roussel Ltd, Walton Manor, Walton, Milton Keynes, Bucks MK7 7AJ, UK.
Till
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Ioannides
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C