in mice: 10 mg/kg/day in corn oil for 25 days potently prevents TCDD-caused cytochrome P450 induction, liver toxicity, and wasting syndrome in mice.

It was tested the ability of CH-223191 to block TCDD-mediated cytochrome P450 expression by using Western blot assay and RT-PCR in HepG2 cells. Treatment with TCDD caused an increase in the level of cytochrome P450 1A1 protein and mRNA compared with the DMSO control. Such cytochrome P450 1A1 induction was inhibited by CH-223191 in dose-dependent manner. After pretreatment with 0.1, 1, or 10 μM CH-223191 for 1 h, HepG2 cells were treated with 3 nM TCDD for 24 h. Cytochrome P450 activity was determined in intact cells by ethoxyresorufin-O-deethylase (EROD) assay. CH-223191 alone had no inductive effects at any concentration, whereas 10 μM flavone slightly increased cytochrome P450 1A1 expression and cytochrome P450 activity. Therefore, these results support the conclusion that CH-223191 has only AhR antagonist effects without agonist-like activity and unlike that observed for flavone.