Comparative effects of flavonoids and model inducers on drug-metabolizing enzymes in rat liver
Comparative effects of flavonoids and model inducers on drug-metabolizing enzymes in rat liver
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DOI：
10.1016/s0300-483x(96)03412-9
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发表时间：
1996-11-15
期刊：
影响因子：
4.5
通讯作者：
Suschetet, M
中科院分区：
文献类型：
--
作者：
CanivencLavier, MC;Vernevaut, MF;Suschetet, M
研究了一些黄酮类化合物（黄酮、二氢黄酮、橘皮素和槲皮素）和模型物质对大鼠的诱导作用，并比较了大鼠体内药物代谢酶的活性和表达。在饮食中添加类黄酮 (0.3% w/w) 2 周不会改变肝脏细胞色素 P450 含量，也不会改变 NADPH-细胞色素 P450 和 NADH-细胞色素 b(5) 还原酶的活性，但会影响 I 相和 II 相酶的活性。黄酮和橘皮素在较小程度上增加了 P450 1A1,2 (EROD) 和 2B1,2 (PROD) 介导的活性以及对硝基苯酚 UDP-葡萄糖醛酸转移酶 (UGT) 和谷胱甘肽转移酶 (GST) 的活性。黄烷酮主要增强 PROD、UGT 和 GST，而槲皮素没有改变任何酶活性。所测试的类黄酮均不会调节 P450 2E1、3A 和 4A 催化的活性。免疫印迹研究表明黄酮和橘子素增加细胞色素 P450 1A 和 2B 形式的表达，而黄酮仅诱导细胞色素 P450 2B。黄酮和较小程度的黄烷酮显着提高了苯酚-UGT 蛋白水平。黄酮和黄烷酮也会增加雄酮和睾酮 UGT，而橘皮素和槲皮素不会增加任何 UGT 亚型。我们得出的结论是，测试的黄酮类化合物特异性影响大鼠肝脏中药物代谢同工酶的表达，其诱导特性取决于其化学结构。
The inducing effects of some flavonoids (flavone, flavanone, tangeretin and quercetin) and model substances have been studied in rats, and the activity and the expression of drug-metabolizing enzymes have been compared in rats. The addition of flavonoids to the diet (0.3% w/w) for 2 weeks did not change the liver cytochrome P450 content nor the activities of the NADPH-cytochrome P450 and NADH-cytochrome b(5) reductases, but it affected the activities of phase I and phase II enzymes. Flavone, and to a lesser extent tangeretin, increased the activities mediated by the P450 1A1,2 (EROD) and 2B1,2 (PROD) as well as the activities of p-nitrophenol UDP-glucuronyl transferase (UGT) and glutathione transferase (GST). Flavanone mainly enhanced PROD, UGT and GST, whereas quercetin did not modify any enzyme activities. None of the tested flavonoids modulated the activities catalyzed by P450 2E1, 3A and 4A. Immunoblotting studies showed that flavone and tangeretin increased the expression of cytochrome P450 1A and 2B forms, whereas flavanone only induced cytochrome P450 2B. Flavone and to a lesser extent flavanone, markedly increased the phenol-UGT protein level. Both flavone and flavanone also increased the androsterone- and testosterone-UGTs, whereas tangeretin and quercetin did not increase any UGT isoform. We concluded that the flavonoids tested specifically affected the expression of the drug-metabolizing isozymes in rat liver, their inducing properties were dependent on their chemical structures.