Liver slices in in vitro pharmacotoxicology with special reference to the use of human liver tissue.
In the early years of research in in vitro pharmacotoxicology liver slices have been used. After a decline in the application of slices in favour of the use of isolated hepatocytes and the isolated perfused liver preparation, the development of the Krumdieck slicer in the 1980s led to a ;comeback' of the technique. This review will focus on the use of human liver, with special reference to the comparison of slices with isolated hepatocytes in in vitro pharmacotoxicology. In addition, an overview on the predictive value of these in vitro systems for drug disposition and toxicity in vivo will be given. Preservation techniques for liver slices and hepatocytes will also be discussed. These techniques ensure an efficient utilization of the scarce human material. For long-term storage of liver slices and hepatocytes, cryopreservation seems most promising. However, cryopreservation is still in its infancy, and reports mainly deal with drug metabolism studies after cryopreservation. Drug toxicity, metabolism and transport data determined in slices and isolated hepatocytes, from both human and animal liver showed good correlation with the corresponding parameters measured in vivo. Therefore, the results obtained in such studies may give rise to more in-depth research on the mechanisms of pharmactoxicology in the human liver.
Olinga
P
P
Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University Hospital, Hanzeplein 1, 9713 EZ Groningen, The Netherlands.
Meijer
D K
DK
Slooff
M J
MJ
Groothuis
G M
GM