• DOI:10.1124/DMD.31.6.773
• Corpus ID: 9558704

Induction of hepatic phase II drug-metabolizing enzymes by 1,7-phenanthroline in rats is accompanied by induction of MRP3.

@article{Wang2003InductionOH,
  title={Induction of hepatic phase II drug-metabolizing enzymes by 1,7-phenanthroline in rats is accompanied by induction of MRP3.},
  author={Sui-Chi Wang and Dylan P. Hartley and Suzanne L Ciccotto and Stella H. Vincent and Ronald B. Franklin and Mi-Sook Kim},
  journal={Drug metabolism and disposition: the biological fate of chemicals},
  year={2003},
  volume={31 6},
  pages={
          773-5
        }
}

• Sui-Chi Wang, D. Hartley, +3 authors Mi-Sook Kim
• Published 1 June 2003
• Biology, Chemistry
• Drug metabolism and disposition: the biological fate of chemicals

The purpose of the present study was to evaluate the effect of 1,7-phenanthroline (PH), which has been proposed to be a selective phase II enzyme inducer, on the gene expression of xenobiotic transporters, as well as hepatic and renal drug-metabolizing enzymes. After oral administration of PH for 3 days to male Sprague-Dawley rats, mRNA levels in liver (75 and 150 mg/kg doses) and kidney (75 mg/kg dose only) were determined using real-time quantitative polymerase chain reaction. At 150 mg/kg/day, PH treatment resulted in significant increases in hepatic mRNA levels of Mrp3 (36-fold), UGT1A6 (20-fold), UGT2B1 (4-fold), and quinone reductase (QR, 5-fold), compared with the vehicle-treated group. Similar increases in Mrp3 (99-fold), UGT1A6 (17-fold), UGT2B1 (3-fold), and QR (11-fold) mRNA levels were observed in the liver after PH treatment of rats at 75 mg/kg/day. In contrast, the expression levels of CYP2C11 and Oatp2 were decreased by approximately 80 and 50%, respectively. In addition, PH (75 mg/kg/day) elicited statistically significant changes in renal gene expression of CYP3A1, UGT1A6, QR, and Mrp3, but the magnitude of renal Mrp3 induction was less than 2-fold over control. Although PH is known to modulate hepatic glucuronidation in vivo, these data indicated that PH induced mRNA levels of the efflux transporter, Mrp3, which may also affect the disposition of xenobiotics.