Immobilized Hepatocytes in Xenobiotic Biotransformation Studies

In Chapter 21 , we described a method for hepatocyte immobilization in agarose threads that enables perfusion of the cells and facilitates varied biomedical studies on the biochemical properties of hepatocytes. Since the liver is the most important and unique organ in metabolic processing of both endogenous and exogenous compounds; this chapter provides details of an application of immobilized and perfused hepatocytes for xenobiotic biotransformation as an indication of many other potential applications. The liver cells possess high nonspecific enzymatic activity toward individual substrates that, however, may be considered specific toward certain chemical groups. These metabolic enzymes, which are genetically determined in the organism, are affected by many exogenous and endogenous factors. The chemical structure of the foreign compound is an important factor for determining its own metabolic fate. It is well known that xenobiotic biotransformation, which takes place predominantly in liver cells, occurs in two phases (1 –3 ). In phase I, the major reaction involved is oxidation catalyzed by enzymes, known as mono-oxygenases or cytochrome P450 species, in addition to other reduction and hydrolytic reactions.