Fraunhofer-Gesellschaft

Publica

Hier finden Sie wissenschaftliche Publikationen aus den Fraunhofer-Instituten.

Human hepatocytes as a tool for hepatotoxicity-testing

 
: Doss, S.; Potschka, H.; Doss, F.; Mitzner, S.; Mitzner, S.; Sauer, M.; Sauer, M.

:

Toxicology letters 258 (2016), Supplement, pp.S283
ISSN: 0378-4274
ISSN: 1879-3169
European Societies of Toxicology (EUROTOX Congress) <52, 2016, Seville>
English
Abstract
Fraunhofer IZI ()

Abstract
Background: Drug induced liver injury (DILI) is the most common cause of liver injury and a rare but serious clinical problem. The hepatotoxicity of many drugs – including the antimycotics – is poorly screened in human models. Antimycotics are involved in approximately 3% of DILI cases. Primary human hepatocytes and hepatoma cell lines are estimated in vitro model systems for hepatotoxicity studies.
Methods: We compared the response of primary human hepatocytes (two donors, 50,000 cells/96-well, medium, 24 h) and an established in-vitro cytotoxicity assay with a standardized permanent cell line (HepG2/C3A, 500,000 cells/24-well, medium, 144 h) incubated with different concentrations of antimycotics (anidulafungin, caspofungin and fluconazole). We determinated the cell viability (XTT, MTT) and CYP1A2 activity (EROD-test). The lowest test concentration of antimycotics was the mean plasma levels after induction of an i.v. therapy (Cmax), as well as the 5-times and 10-times concentrations of Cmax were analysed (+ negative control: medium and positive control: acetaminophen).
Results: In both models all antimycotics are associated with slightly hepatotoxicity in the Cmax concentration; Anidulafungin showed a stronger hepatotoxicity in higher concentration in the MTT/XTT-test. The activity of the CYP1A2-enzyme was not affected by anidulafungin; in contrast, fluconazol and caspofungin led to a significantly lower activity in all concentrations in both cell-models.
Conclusion: The standardised cytotoxicity assay with the permanent cell line C3A showed the similar results in hepatotoxicity-testing of antimycotics as primary human hepatocytes and may represents cost effective tool for hepatotoxicity-testing.

: http://publica.fraunhofer.de/documents/N-467429.html