دورية أكاديمية
Cryopreservation of rat precision-cut liver slices by ultrarapid freezing: influence on phase I and II metabolism and on cell viability upon incubation for 24 hours
| العنوان: | Cryopreservation of rat precision-cut liver slices by ultrarapid freezing: influence on phase I and II metabolism and on cell viability upon incubation for 24 hours |
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| المؤلفون: | Vanhulle, V. P., Martiat, G. A., Verbeeck, Roger-K, Horsmans, Yves, Buc Calderon, Pedro, Eeckhoudt, S L, Taper, Henryk S, Delzenne, Nathalie M. |
| المساهمون: | UCL - MD/FARM - Ecole de pharmacie, UCL - MD/MINT - Département de médecine interne, UCL - (SLuc) Service de gastro-entérologie, UCL - (SLuc) Service de biologie hématologique, UCL - (SLuc) Centre de theÌrapie tissulaire et cellulaire |
| المصدر: | Life Sciences, Vol. 68, no. 21, p. 2391-2403 (2001) |
| بيانات النشر: | Elsevier Inc. |
| سنة النشر: | 2001 |
| المجموعة: | DIAL@UCL (Université catholique de Louvain) |
| مصطلحات موضوعية: | Acetaminophen, Adenosine Triphosphate, Animals, Biotransformation, Blotting, Western, Cell Survival, Cryopreservation, Cytochrome P-450 Enzyme System, Freezing, Glycogen, Hepatocytes, Isoenzymes, L-Lactate Dehydrogenase, Liver, Male, Midazolam, Organ Culture Techniques, Organ Preservation, Rats, Wistar, Rat, Liver slices |
| الوصف: | Several cryopreservation methods for precision-cut rat liver slices (PCLS) have been proposed, allowing a short-term (a few hours) maintainance of viability and functionality upon thawing. The aim of the present study was to test the metabolic capacity of PCLS cryopreserved by an ultrarapid method. The biotransformation of paracetamol to its glucuronide and sulfate conjugates and of midazolam to its hydroxylated metabolites was studied in thawed PCLS incubated for 24 hours at 37 degrees C in Williams' medium E. In addition, protein levels of the key enzymes involved in these metabolic reactions, i.e. UGT1A1, ST1A1, CYP2E1 and CYP3A2 were determinated. In addition, biological markers of cell function (ATP and glycogen levels) and toxicity (LDH leakage in the medium) were also measured. Compared to controls (non cryopreserved PCLS), CYP3A2 activity and content and CYP2E1 content were maintained at the same level all along the incubation, whereas paracetamol glucuronidation and sulfation dropped to 24 and 21% of the control value, respectively, immediately after thawing. Freezing-thawing conditions also modified cell functionality, leading to a lower intracellular ATP and glycogen content, and an increase in cell lysis, as shown by LDH released in the medium. The results of this study suggest that cryopreserved PCLS are able to maintain some phase I activities for 24 hours after thawing whereas some phase II metabolic capacities are not maintained. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0024-3205 1879-0631 |
| العلاقة: | boreal:8835; http://hdl.handle.net/2078.1/8835Test; info:pmid/11350010; urn:ISSN:0024-3205; urn:EISSN:1879-0631 |
| DOI: | 10.1016/S0024-3205(01)01031-1 |
| الإتاحة: | https://doi.org/10.1016/S0024-3205Test(01)01031-1 http://hdl.handle.net/2078.1/8835Test |
| حقوق: | info:eu-repo/semantics/restrictedAccess |
| رقم الانضمام: | edsbas.98EA814 |
| قاعدة البيانات: | BASE |
| تدمد: | 00243205 18790631 |
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| DOI: | 10.1016/S0024-3205(01)01031-1 |