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Research ArticleArticle

Drug Metabolizing Capacity of Cryopreserved Human, Rat, and Mouse Liver Parenchymal Cells in Suspension

Pablo Steinberg, Thomas Fischer, Sandra Kiulies, Katja Biefang, Karl-Ludwig Platt, Franz Oesch, Thomas Böttger, Clemens Bulitta, Peter Kempf and Jan Hengstler
Drug Metabolism and Disposition December 1999, 27 (12) 1415-1422;
Pablo Steinberg
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Thomas Fischer
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Sandra Kiulies
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Katja Biefang
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Karl-Ludwig Platt
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Franz Oesch
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Thomas Böttger
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Clemens Bulitta
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Peter Kempf
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Abstract

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°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 glutathioneS-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.

Footnotes

  • Send reprint requests to: Dr. Pablo Steinberg, Institut für Ernährungswissenschaft, Universität Potsdam, Arthur Scheunert-Allee 114–116, 14558 Bergholz-Rehbruecke. Germany. E-mail: steinber{at}rz.uni-potsdam.de

  • ↵1 Current address: Institut für Toxikologie, Universität Mainz, Obere Zahlbacher Str. 67, 55131 Mainz.

  • ↵2 Current address: Lehrstuhl für Ernährungstoxikologie, Institut für Ernährungswissenschaft, Universität Potsdam, Arthur Scheunert-Alle 114–116, 14558 Bergholz-Rehbrücke.

  • ↵3 Current address: Klinik und Poliklinik für Allgemein- und Abdominalchirurgie, Universität Mainz, Langenbeckstr. 1, 55131 Mainz.

  • ↵4 Current address: Chirurgische Abteilung, Stadtkrankenhaus Rüsselsheim, August Bebel Str. 59, 65428 Rüsselsheim, Germany.

  • This study was supported by the Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie, Germany (Grant 0311258).

  • Abbreviations used are::
    PC
    parenchymal cells
    ECOD
    7-ethoxycoumarin-O-deethylase
    EROD
    7-ethoxyresorufin-O-deethylase
    GST
    glutathioneS-transferase
    UDP-GT
    UDP-glucuronosyltransferase
    MUF
    4-methylumbelliferone
    HOBI
    4-hydroxybiphenyl
    ST
    sulfotransferase
    LDH
    lactate dehydrogenase
    HBSS
    Hank's balanced salt solution
    DMSO
    dimethyl sulfoxide
    OHT
    hydroxytestosterone
    • Received May 10, 1999.
    • Accepted September 1, 1999.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 27 (12)
Drug Metabolism and Disposition
Vol. 27, Issue 12
1 Dec 1999
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Research ArticleArticle

Drug Metabolizing Capacity of Cryopreserved Human, Rat, and Mouse Liver Parenchymal Cells in Suspension

Pablo Steinberg, Thomas Fischer, Sandra Kiulies, Katja Biefang, Karl-Ludwig Platt, Franz Oesch, Thomas Böttger, Clemens Bulitta, Peter Kempf and Jan Hengstler
Drug Metabolism and Disposition December 1, 1999, 27 (12) 1415-1422;

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Research ArticleArticle

Drug Metabolizing Capacity of Cryopreserved Human, Rat, and Mouse Liver Parenchymal Cells in Suspension

Pablo Steinberg, Thomas Fischer, Sandra Kiulies, Katja Biefang, Karl-Ludwig Platt, Franz Oesch, Thomas Böttger, Clemens Bulitta, Peter Kempf and Jan Hengstler
Drug Metabolism and Disposition December 1, 1999, 27 (12) 1415-1422;
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