Nho C W, Jeffery E
Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Toxicol Appl Pharmacol. 2001 Jul 15;174(2):146-52. doi: 10.1006/taap.2001.9207.
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.
十字花科蔬菜含有被称为硫代葡萄糖苷的次生代谢产物，这些产物分解后形成的物质会上调肝脏解毒酶。我们之前已经表明，来自抱子甘蓝的四种主要硫代葡萄糖苷分解产物的混合物相互作用，可产生对II期解毒酶的协同诱导作用。在此，我们检验了这样一个假设，即这种协同作用发生在转录水平，并且是由于口服双功能诱导剂吲哚 - 3 - 甲醇（I3C）和单功能诱导剂克拉烯（1 - 氰基 - 2 - 羟基 - 3 - 丁烯）之间的相互作用所致。成年雄性大鼠通过灌胃给予玉米油（赋形剂）；克拉烯（50毫克/千克）、I3C（56毫克/千克），或所示剂量的克拉烯与I3C混合物。经口服，单独的I3C以及与克拉烯一起使用时均会显著诱导CYP1A活性和CYP1A1 mRNA水平，而单独的克拉烯对CYP1A活性或mRNA水平无显著影响。克拉烯和I3C分别单独诱导谷胱甘肽S - 转移酶（GST）和醌还原酶（QR）活性。克拉烯与I3C的混合物诱导GST和QR的程度显著大于单独处理诱导作用的总和。总GST活性的上调程度不如QR，可能是因为一些亚基未表现出这种效应。GST Ya2 mRNA显示出克拉烯和I3C的协同上调，而Yc1和Yc2仅表现出相加反应。我们推测这种不同的调节部分是由于与GST Yc1/Yc2亚基调节区域相比，GST Ya2调节区域内抗氧化反应元件和外源性物质反应元件的基因序列存在差异。
