A rapid and simple method for cryopreservation of human liver slices

被引:38
作者
de Kanter, R
Olinga, P
Hof, I
de Jager, M
Verwillegen, WA
Slooff, MJH
Koster, HJ
Meijer, DKF
Groothuis, GMM
机构
[1] Groningen Utrecht Inst Drug Explorat, Dept Pharmacokinet & Drug Delivery, NL-9713 AV Groningen, Netherlands
[2] Solvay Duphar BV, Drug Safety Dept, NL-1380 DA Weesp, Netherlands
[3] Univ Groningen Hosp, Dept Surg, GUIDE, Div Hepatobiliary Surg & Liver Transplantat, NL-9713 GZ Groningen, Netherlands
关键词
D O I
10.1080/004982598239533
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1. Precision-cut liver slices represent a suitable and convenient in vitro preparation for studying metabolism and toxicity mechanisms of drugs and toxic chemicals. Particularly in the case of human liver slices, cryopreservation would enable more efficient utilization of this scarce and irregularly available tissue. 2. Liver slices from consecutive human livers were cryopreserved using a method previously developed for rat and monkey liver slices. This procedure involves incubation in 12% dimethyl sulphoxide for 30 mir. on ice and direct immersion into liquid nitrogen. 3. Functional integrity of cryopreserved human liver slices, as compared with that of fresh liver slices, was maintained at 66+/-8% (alanine aminotransferase activity retained in the slices), 78+/-7% (urea synthesis), 88+/-14% (testosterone hydroxylation), 84+/-7% (N-deethylation of lidocaine) and 88+/-10% (total O-deethylation of 7-ethoxycoumarin). The ratios of testosterone metabolites did not change on cryopreservation. 4. These results show that the cryopreserved human liver slices retained the measured drug metabolism activities. Therefore, this cryopreservation method is suitable for storing liver slices to be used for comparing drug metabolism patterns, at least qualitatively, between species.
引用
收藏
页码:225 / 234
页数:10
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