PMID: 9443845Mar 14, 1998Paper

Effect of human liver source on the functionality of isolated hepatocytes and liver slices

Drug Metabolism and Disposition : the Biological Fate of Chemicals
P OlingaG M Groothuis

Abstract

In vitro experiments using human liver tissue to study drug metabolism and transport are usually performed and interpreted without real consideration of the differences in procurement of the tissue, if it is obtained from different sources. Therefore, in this study the functionality of isolated hepatocytes and liver slices prepared either from healthy human liver tissue obtained from patients undergoing partial hepatectomy [livers from partial hepatectomy (PH-livers)] or from donor tissue remaining after reduced-size or split-liver transplantation [livers from transplantation (Tx-livers)] was compared. From each liver sample, both liver slices and hepatocytes were prepared and compared with respect to viability and drug disposition. The viability of hepatocytes was assessed by trypan blue exclusion, ATP content, and energy charge and that of liver slices by potassium retention. In both preparations phase I metabolism was studied using lidocaine and testosterone as substrates, whereas phase I and II metabolism was assessed with 7-ethoxycoumarin. The membrane transport capability of the hepatocytes was investigated by measuring the uptake of taurocholic acid. The hepatocytes from PH-livers and Tx-livers showed similar viabilities...Continue Reading

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