Cw. Nho et E. Jeffery, The synergistic upregulation of phase II detoxification enzymes by glucosinolate breakdown products in cruciferous vegetables, TOX APPL PH, 174(2), 2001, pp. 146-152
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 breakd
own products from Brussels sprouts interact to produce synergistic inductio
n of phase II detoxification enzymes. Here we tested the hypothesis that th
is synergism is at the level of transcription and is due to the interaction
between the oral bifunctional inducer, indole-3-carbinol (I3C), and monofu
nctional inducer, crambene (1-cyano 2-hydroxy 3-butene). Adult male rats we
re treated by gavage with either corn oil (vehicle); crambene (50 mg/kg), I
3C (56 mg/kg), or a mix of crambene and I3C at the doses shown. Given orall
y, I3C alone and crambene with I3C caused significant induction of CYP1A ac
tivity and CYP1A1 mRNA levels, whereas crambene alone had no significant ef
fect on CYP1A activity or mRNA levels. Crambene and I3C individually caused
induction of glutathione S-transferase (GST) and quinone reductase (QR) ac
tivity. The mixture of crambene and IX caused induction of GST and QR that
was significantly greater than the sum of the induction by individual treat
ments. Upregulation of total GST activity was not as great as that of QR, p
ossibly because some subunits did not show this effect. GST Ya2 mRNA showed
a synergistic upregulation by crambene and I3C, while Yc1 and Yc2 showed o
nly an additive response. We speculate that this different regulation is pa
rtly due to differences in gene sequences within the antioxidant response e
lement and xenobiotic response element in the regulatory region of GST Ya2
compared to those within the regulatory region of the Yc1/Yc2 subunits. (C)
2001 Academic Press.