Drug metabolizing capacity of cryopreserved human, rat, and mouse liver parenchymal cells in suspension

The phase I and phase II drug-metabolizing capacity of freshly isolated and cryopreserved parenchymal cells (PC) from human, rat, and mouse liver held in suspension at 37 degrees C for up to 120 min after thawing was compared . Although 7-ethoxycoumarin-O-deethylase activity was strongly reduced in f reshly isolated as well as in cryopreserved PC from human, rat, and mouse l iver after 120 min, 7-ethoxyresorufin-O-deethylase activity as well as the profile and formation rates of hydroxylated testosterone metabolites in gen eral remained constant throughout the 2-h incubation period in cryopreserve d PC from all three species and was similar to that measured in freshly iso lated PC. The activity of glutathione S-transferase (GST) and that of UDP-g lucuronosyltransferase (UDP-GT) toward 4-methylumbelliferone significantly decreased, whereas the activities of UDP-GT activity toward 4-hydroxybiphen yl and sulfotransferase in cryopreserved human PC were similar to those mea sured in freshly isolated PC. The activities of GST, UDP-GT toward 4-methyl umbelliferone, and sulfotransferase in cryopreserved rat PC showed a signif icant decrease when compared with the activities in freshly isolated PC. Th e phase II enzyme activities in cryopreserved mouse PC proved to be far mor e stable, being similar to the activities of freshly isolated mouse PC at a ll four time points measured with the exception of GST, which showed a deca y from t = 60 min onward. In conclusion, phase I drug-metabolizing enzyme a ctivities in cryopreserved human, rat, and mouse PC are very similar to tho se of freshly isolated PC, whereas phase II enzyme activities are affected by cryopreservation.