Intestinal responses to xenobiotics

The gastrointestinal tract represents the first barrier met by the exogenou s compounds of food or orally delivered drugs. To be transferred to the who le body, drugs and xenobiotics have first to pass through the intestinal ep ithelium, where detoxification systems have to minimize the potential of da mage from toxic xenobiotics. However, most studies on xenobiotic-metabolizi ng enzymes have focused on liver enzymes. Such a situation may be explained by the fact that this organ is the site of toxification/detoxification for both endogenous and exogenous compounds, and also because adequate in vitr o hepatocytes models have been available for a long time. By contrast, norm al cellular models for the in vitro study of the intestinal processes of bi otransformation still remain difficult to obtain. In the present report we will thus focus on the most commonly used models, which are Caco-2 cells an d their derivative clones, and we will report recent procedures that allow the isolation of normal enterocytes which maintain their functions and inte grity for several hours or even several days. Their respective performance arid advantages for the study of the induction of the drug-metabolizing enz ymes will be discussed. (C) 2001 Elsevier Science Ltd. All rights reserved.