Intestinal responses to xenobiotics.
The gastrointestinal tract represents the first barrier met by the exogenous compounds of food or orally delivered drugs. To be transferred to the whole body, drugs and xenobiotics have first to pass through the intestinal epithelium, where detoxification systems have to minimize the potential of damage from toxic xenobiotics. However, most studies on xenobiotic-metabolizing 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 vitro hepatocytes models have been available for a long time. By contrast, normal cellular models for the in vitro study of the intestinal processes of biotransformation still remain difficult to obtain. In the present report we will thus focus on the most commonly used models, which are Caco-2 cells and their derivative clones, and we will report recent procedures that allow the isolation of normal enterocytes which maintain their functions and integrity for several hours or even several days. Their respective performance and advantages for the study of the induction of the drug-metabolizing enzymes will be discussed.
Carrière
V
V
Université Pierre et Marie Curie, INSERM U505, 15 rue de l'Ecole de Médecine, 75006 Paris, France.
Chambaz
J
J
Rousset
M
M
D000818:Animals; D018938:Caco-2 Cells; D003035:Cobalt / Q000494:pharmacology; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D020895:Enterocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008658:Inactivation, Metabolic; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D012333:RNA, Messenger / Q000378:metabolism; D015262:Xenobiotics / Q000378:metabolism / Q000633:toxicity*; D019324:beta-Naphthoflavone / Q000494:pharmacology
D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D015262:Xenobiotics; D003035:Cobalt; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D019363:Cytochrome P-450 CYP1A1; D051544:Cytochrome P-450 CYP3A; C018021:cobaltous chloride