1. The influence of short-term cold storage in University of Wisconsin organ preservation solution (UW) on the ability to metabolize lidocaine, testosterone and 7-ethoxycoumarin in isolated human and cynomolgus monkey (Macaca fascicularis) hepatocytes and liver slices has been investigated. 2. The human liver tissue was obtained from two different sources, i.e. healthy liver tissue from patients undergoing partial hepatectomy because of metastases of colorectal carcinoma (PH livers) and donor tissue remaining as surgical waste after reduced size or split liver transplantation (Tx livers). Tx livers were perfused in situ with ice-cold UW avoiding warm ischaemia. This in contrast with PH livers, where the operation caused warm ischaemia for 5-90 min. 3. Liver slices and hepatocytes from cynomolgus monkey liver showed comparable metabolic rates for the substrates tested, indicating that all hepatocytes in the slice are participating in the biotransformation of the substrates. These monkey liver preparations can be stored up to 18 h with only a slight loss of their metabolic capacity. 4. Liver slices and isolated hepatocytes from the Tx livers as well as isolated cells from the PH livers could also be stored up to 18 h without losing metabolic capacity. However, for liver slices prepared from PH livers cold storage is not recommended, because metabolic function was reduced by approximately 40% after 18 h.
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 min 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.
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