4-nonylphenol attenuates dexamethasone induction of CYP2B and CYP3A in FVB/NJ mice

4-nonylphenol (4-NP) binds and activates both the estrogen receptor (ER) and the Pregnane X receptor (PXR). Recent work in our lab demonstrated that 7-day exposures of mice to 4-NP induced CYP2B10, but had no effect on CYP3A. In contrast, gestational/chronic treatments of young and chronic treatments of 32 weeks in adults reduced CYP3A levels and attenuated induction of CYP2B10. Therefore, we were interested in determining if 4-NP could reduce the ability of FVB/NJ mice to respond to Constitutive androstane receptor (CAR) or PXR ligands. Mice were treated orally for six weeks with honey as the control or 50 mg/kg/day 4-NP in honey. After six weeks, the control and 4-NP treated mice were further split into groups of six, and were injected for three days with corn oil, dexamethasone (DEX) (PXR activator), or 4-bis [2-(3, 5-dichloropyridyloxy)] benzene also known as TCPOBOP (TC), (CAR activator). Mice were euthanized and RNA and microsomes were prepared from liver for immunoblot analysis of CYP3A and CYP2B, which are transcriptionally activated by PXR and CAR respectively. (Abstract shortened by UMI.