Measurement of Cytochrome P450 Enzyme Induction an

Authors: Robim M Rodrigues Joery De Kock Tatyana Y Doktorova Vera Rogiers Tamara Vanhaecke

Publish Date: 2015

Volume: , Issue: , Pages: 279-285

PDF Link

Abstract

Cytochrome P450 enzymes are a diverse group of catalytic enzymes in the liver that are mainly responsible for the biotransformation of organic substances Cytochrome P450 activity as well as both its induction and inhibition are key factors in drug biotransformation and can be involved in deactivation activation detoxification and toxification processes Thus the modulation of cytochrome P450 activity is an important parameter when evaluating the potential toxicity of chemical compounds using an in vitro system The cytochrome P450 3A subfamily proteins are among the most important drugmetabolizing enzymes in human liver and are responsible for about half of all cytochrome P450dependent drug oxidations In vitro these enzymes are active not only in primary human hepatocyte cultures but also in differentiated human hepatoma HepaRG cells The present protocol describes the culture of cryopreserved differentiated HepaRG cells and the evaluation of its cytochrome P450 activity upon exposure to a chemical compound using a commercially available luminogenic cytochrome P450 assay This in vitro model can be used to monitor the induction and inhibition of cytochrome P450 3A following exposure to a particular test compoundThis work has received funding from grants of the Fund for Scientific Research in Flanders FWOVlaanderen GO16312N the European Community’s Seventh Framework Programme FP7/2007–2013 under grant agreement no 266838 DETECTIVE and no 266777 HEMIBIO and from the Brussels research fund INNOVIRIS Brustem

Keywords: