Up-regulation of cytochrome P450 and phase II enzymes by xenobiotics in precision-cut tissue slices

Abstract

1. Induction of the drug-metabolising enzyme systems is a major cause of clinically relevant drug interactions. The potential of a drug to engage in such interactions may be assessed in in vitro systems such as precision-cut tissue slices.

2. Precision-cut tissue slices have a number of important advantages compared with the use of cells in culture, especially when tissues with a heterogeneous cellular population are concerned.

3. Extensive studies concerned with the induction of cytochrome P450 and Phase II enzymes in precision-cut tissue slices from various animal and human tissues, such as liver, lung and intestine, using established inducing agents have revealed that slices mimic the in vivo situation.

4. Precision-cut tissue slices is a reliable, informative and cost-effective technique for assessing the potential of chemicals to up-regulate drug-metabolising enzyme systems.

Keywords::

• Precision-cut tissue slices
• enzyme induction
• cytochromes P450
• phase II metabolism