Back to Search
Start Over
The utility of cold-preserved human hepatocytes in studies on cytochrome P450 induction and hepatic drug transport.
- Source :
-
Xenobiotica; the fate of foreign compounds in biological systems [Xenobiotica] 2013 Sep; Vol. 43 (9), pp. 785-91. Date of Electronic Publication: 2013 Apr 09. - Publication Year :
- 2013
-
Abstract
- Human hepatocytes that had been cold-preserved in SureTran(TM) matrix (Abcellute Ltd, Cardiff, UK) were used for studies on cell viability, cytochrome P450 (CYP) 3A4, 2B6 and 1A2 induction and hepatic drug transporters. It has recently been shown that basal CYP activities are maintained in cold-preserved hepatocytes (Palmgren et al., 2012). After 5 d of cold preservation, the viability was still more than 70%, and after 8 d it was around 60%. In hepatocytes that had been cold-preserved for 3 d, the activity of CYP3A4 was induced around 15-fold upon treatment with 8 µM rifampicin for 72 h. For CYP2B6, the activity was induced 4- to 16-fold in hepatocytes that had been cold-preserved for 3 d and thereafter treated with 1 mM phenobarbital for 72 h. The activity of CYP1A2 was low and close to the limit of detection in non-treated cells that had been cold-preserved for up to 3 d, while the activity increased in cells treated with 0.3-25 µM β-naphthoflavone for 72 h. CYP3A4, 2B6 and 1A2 mRNA levels were only determined with hepatocytes from one donor and increased upon treatment with the inducers. Hepatic uptakes of estrone-3-sulfate, taurocholate, ipratropium and rosuvastatin were stable in human hepatocytes that had been cold-preserved for up to 2 d. In summary, cold-preserved human hepatocytes demonstrate retained viability and can advantageously be used for in vitro induction studies and for studies of hepatic uptake transporters.
- Subjects :
- Cell Culture Techniques
Cell Survival
Cells, Cultured
Estrone analogs & derivatives
Estrone pharmacokinetics
Fluorobenzenes pharmacokinetics
Hepatocytes drug effects
Humans
Ipratropium pharmacokinetics
Organic Anion Transporters metabolism
Organic Anion Transporters physiology
Phenobarbital pharmacology
Pyrimidines pharmacokinetics
RNA, Messenger metabolism
Rifampin pharmacokinetics
Rifampin pharmacology
Rosuvastatin Calcium
Sulfonamides pharmacokinetics
Taurocholic Acid pharmacokinetics
Cytochrome P-450 CYP3A metabolism
Hepatocytes metabolism
Liver metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1366-5928
- Volume :
- 43
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Xenobiotica; the fate of foreign compounds in biological systems
- Publication Type :
- Academic Journal
- Accession number :
- 23570537
- Full Text :
- https://doi.org/10.3109/00498254.2013.767952