The synergistic upregulation of phase II detoxification enzymes by glucosinolate breakdown products in cruciferous...

Cruciferous vegetables contain secondary metabolites termed glucosinolates that break down to products that upregulate hepatic detoxification enzymes. We have previously shown that a mixture of four major glucosinolate breakdown products from Brussels sprouts interact to produce synergistic induction of phase II detoxification enzymes. Here we tested the hypothesis that this synergism is at the level of transcription and is due to the interaction between the oral bifunctional inducer, indole-3-carbinol (I3C), and monofunctional inducer, crambene (1-cyano 2-hydroxy 3-butene). Adult male rats were treated by gavage with either corn oil (vehicle); crambene (50 mg/kg), I3C (56 mg/kg), or a mix of crambene and I3C at the doses shown. Given orally, I3C alone and crambene with I3C caused significant induction of CYP1A activity and CYP1A1 mRNA levels, whereas crambene alone had no significant effect on CYP1A activity or mRNA levels. Crambene and I3C individually caused induction of glutathione S-transferase (GST) and quinone reductase (QR) activity. The mixture of crambene and I3C caused induction of GST and QR that was significantly greater than the sum of the induction by individual treatments. Upregulation of total GST activity was not as great as that of QR, possibly because some subunits did not show this effect. GST Ya2 mRNA showed a synergistic upregulation by crambene and I3C, while Yc1 and Yc2 showed only an additive response. We speculate that this different regulation is partly due to differences in gene sequences within the antioxidant response element and xenobiotic response element in the regulatory region of GST Ya2 compared to those within the regulatory region of the Yc1/Yc2 subunits.