RT Journal Article SR Electronic T1 ABSORPTION/METABOLISM OF SULFORAPHANE AND QUERCETIN, AND REGULATION OF PHASE II ENZYMES, IN HUMAN JEJUNUM IN VIVO JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 805 OP 813 DO 10.1124/dmd.31.6.805 VO 31 IS 6 A1 Niclas Petri A1 Christer Tannergren A1 Birgit Holst A1 Fred A. Mellon A1 Yongping Bao A1 Geoff W. Plumb A1 Jim Bacon A1 Karen A. O'Leary A1 Paul A. Kroon A1 Lars Knutson A1 Patrik Forsell A1 Thomas Eriksson A1 Hans Lennernas A1 Gary Williamson YR 2003 UL http://dmd.aspetjournals.org/content/31/6/805.abstract AB For the first time the human intestinal effective permeability, estimated from the luminal disappearance and intestinal metabolism of phytochemicals, sulforaphane and quercetin-3,4′-glucoside, as well as the simultaneous changes in gene expression in vivo in enterocytes, has been studied in the human jejunum in vivo (Loc-I-Gut). Both compounds as components of an onion and broccoli extract could readily permeate the enterocytes in the perfused jejunal segment. At the physiologically relevant, dietary concentration tested, the average effective jejunal permeability (Peff) and percentage absorbed (± S.D.) were 18.7 ± 12.6 × 10-4 cm/s and 74 ± 29% for sulforaphane and 8.9 ± 7.1 × 10-4 cm/s and 60 ± 31% for quercetin-3,4′-diglucoside, respectively. Furthermore, a proportion of each compound was conjugated and excreted back into the lumen as sulforaphane-glutathione and quercetin-3′-glucuronide. The capacity of the isolated segment to deconjugate quercetin from quercetin-3,4′-diglucoside during the perfusion was much higher than the β-glucosidase activity of the preperfusion jejunal contents, indicating that the majority (79–100%) of the β-glucosidase capacity derives from the enterocytes in situ. Simultaneously, we determined short-term changes in gene expression in exfoliated enterocytes, which showed 2.0 ± 0.4-fold induction of glutathione transferase A1 (GSTA1) mRNA (p < 0.002) and 2.4 ± 1.2-fold induction of UDP-glucuronosyl transferase 1A1 (UGT1A1) mRNA (p < 0.02). The changes in gene expression were also seen in differentiated Caco-2 cells, where sulforaphane was responsible for induction of GSTA1 and quercetin for induction of UGT1A1. These results show that food components have the potential to modify drug metabolism in the human enterocyte in vivo very rapidly. The American Society for Pharmacology and Experimental Therapeutics