Short-term maintenance of phase I and II metabolism in precision-cut liver slices in dynamic organ culture.
Testosterone and 7-ethoxycoumarin were used as substrates to quantify the maintenance of phase I and II enzymes in precision-cut rat liver slices in dynamic organ culture. Testosterone hydroxylations, 7-ethoxycoumarin O-deethylation, 7-hydroxycoumarin sulfate, and 7-hydroxycoumarin glucuronide formation were all maintained at initial levels in the slice incubation media after incubation for up to 4 hr. The activities of various cytochrome P450 isozymes, measured using the stereospecific and regiospecific hydroxylation of testosterone and the maintenance of phase I and II metabolism using 7-ethoxycoumarin, are therefore suggested to be stable over short-term incubations in a physiological buffer. The testosterone hydroxylation assay is also suggested as a versatile slice metabolic viability marker for various P450 activities over longer periods.
Ekins
S
S
Department of Medicine, University of Aberdeen, Indianapolis, IN 46285, USA.
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000378:metabolism*; D003374:Coumarins / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000378:metabolism*
D018931:Antineoplastic Agents, Hormonal; D003374:Coumarins; D007527:Isoenzymes; C017299:7-ethoxycoumarin; D013739:Testosterone; D003577:Cytochrome P-450 Enzyme System