RT Journal Article
SR Electronic
T1 Short-term maintenance of phase I and II metabolism in precision-cut liver slices in dynamic organ culture.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 364
OP 366
VO 24
IS 3
A1 S Ekins
YR 1996
UL http://dmd.aspetjournals.org/content/24/3/364.abstract
AB 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.