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 freshly isolated as well as in cryopreserved PC from human, rat, and mouse liver after 120 min, 7-ethoxyresorufin-O-deethylase activity as well as the profile and formation rates of hydroxylated testosterone metabolites in general remained constant throughout the 2-h incubation period in cryopreserved PC from all three species and was similar to that measured in freshly isolated PC. The activity of glutathione S-transferase (GST) and that of UDP-glucuronosyltransferase (UDP-GT) toward 4-methylumbelliferone significantly decreased, whereas the activities of UDP-GT activity toward 4-hydroxybiphenyl and sulfotransferase in cryopreserved human PC were similar to those measured in freshly isolated PC. The activities of GST, UDP-GT toward 4-methylumbelliferone, and sulfotransferase in cryopreserved rat PC showed a significant decrease when compared with the activities in freshly isolated PC. The phase II enzyme activities in cryopreserved mouse PC proved to be far more stable, being similar to the activities of freshly isolated mouse PC at all four time points measured with the exception of GST, which showed a decay from t = 60 min onward. In conclusion, phase I drug-metabolizing enzyme activities in cryopreserved human, rat, and mouse PC are very similar to those of freshly isolated PC, whereas phase II enzyme activities are affected by cryopreservation.
Steinberg
P
P
Institut für Toxikologie, Universität Mainz, Mainz, Germany. steinber@rz.uni-potsdam.de
Fischer
T
T
Kiulies
S
S
Biefang
K
K
Platt
K L
KL
Oesch
F
F
Böttger
T
T
Bulitta
C
C
Kempf
P
P
Hengstler
J
J
D000818:Animals; D001713:Biphenyl Compounds / Q000378:metabolism; D015925:Cryopreservation; D014453:Glucuronosyltransferase / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D006923:Hymecromone / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley
D001713:Biphenyl Compounds; D006923:Hymecromone; C019046:4-phenylphenol; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase