Inflammation et métabolisme des médicaments

Abstract

Decreased drug metabolism, hyperbilirubinemia and intrahepatic cholestasis are frequently observed dur- ing inflammation. Additionally, it has long been appre- ciated that exposure to drug metabolism-inducing xenobiotics can impair immune function. The nuclear receptor CAR (constitutive androstane receptor or NR1I3) and PXR (pregnane X receptor, NR1I2) con- trol phase I (cytochrome P450 2B and 3A), phase II (GSTA, UGT1A1), and transporter (MDR1, SLC21A6, MRP2) genes involved in drugs metabolism, bile acids and bilirubin clearance in response to xenobiotics. It is well known that inflammation, through the activa- tion of NF-kappaB pathway, leads to a decrease of CAR, PXR and RXRα expression and the expression of their target genes. In addition, a new study reveals the mutual repression between PXR and NF-kappaB signal- ing pathways, providing a molecular mechanism linking xenobiotic metabolism and inflammation.