Evaluation of the metabolism and hepatotoxicity of xenobiotics utilizing precision-cut slices

Abstract

1. Precision-cut liver slices are a valuable in vitro model system to study the metabolism and toxicity of xenobiotics. Liver slices retain tissue architecture so that all cell types are present and intercellular communication between the various cell types is retained.

2. Precision-cut liver slices from humans and other species have been used to study pathways of phase I (e.g. cytochrome P450-dependent biotransformations) and II (e.g. conjugation with D-glucuronic acid, sulphate and glutathione) metabolism of a wide range of xenobiotics.

3. Liver slices can also be employed to investigate the induction and inhibition of xenobiotic metabolizing enzymes and to obtain kinetic data on the rates of metabolism of xenobiotics.

4. Precision-cut liver slices from humans and other species have been used to study the toxicity of a wide variety of xenobiotics. Toxicity can be assessed by various techniques including gene expression, morphological examination and a wide range of biochemical endpoints.

5. Precision-cut liver slices can be utilized to examine species differences in hepatic xenobiotic metabolism and xenobiotic-induced toxicity, thus permitting comparisons between animal species and humans.

Keywords::

• Precision-cut liver slices
• xenobiotic metabolism
• cytochrome P450
• hepatotoxicity
• species differences