Involvement of UDP-glucuronosyltranferases and sulfotransferases in the liver and intestinal first-pass metabolism of seven flavones in C57 mice and humans in vitro
Involvement of UDP-glucuronosyltranferases and sulfotransferases in the liver and intestinal first-pass metabolism of seven flavones in C57 mice and humans in vitro
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UDP-葡萄糖醛酸基转移酶和磺基转移酶参与 C57 小鼠和人体外七种黄酮的肝脏和肠道首过代谢
DOI：
10.1016/j.fct.2012.01.018
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发表时间：
2012-05-01
影响因子：
4.3
通讯作者：
Liu, Zhongqiu
中科院分区：
文献类型：
--
作者：
Tang, Lan;Feng, Qian;Liu, Zhongqiu
本研究调查了参与UDP-葡萄糖醛酸转移酶和磺基转移酶在广泛的肝脏和肠道首过葡萄糖醛酸化和硫酸化的黄酮在小鼠和人类。七个结构相似的单和二羟基黄酮被选为模型化合物。采用人肝、C57小鼠肝和肠59组分以及C57肠灌注模型。在人类和C57小鼠中，发现所有选定的黄酮被葡萄糖醛酸化，其中7-OH基团的速率最高。相反，具有3-OH基团的黄酮根本不被硫酸化。在体外和原位，葡萄糖醛酸化和硫酸化在人和小鼠中均优先选择4 '-和7-OH。在人和小鼠中观察到所有黄酮的葡萄糖醛酸化和硫酸化存在差异，这是基于羟基的取代位置。S9组分可准确模拟葡萄糖醛酸化（对于具有4 '-或7-OH的黄酮，相关曲线斜率为0.7988）和硫酸化（相关曲线斜率为0.9834）。总之，硫酸化和葡萄糖醛酸化的黄酮是区域特异性和物种依赖性。小鼠离体小肠的硫酸化和葡萄糖醛酸化与在体小肠的硫酸化和葡萄糖醛酸化具有良好的相关性。(C)2012爱思唯尔有限公司保留所有权利。
The present study investigated the involvement of UDP-glucuronosyltransferase and sulfotransferase in the extensive liver and intestinal first-pass glucuronidation and sulfation of flavones in both mice and humans. Seven structurally similar mono- and di-hydroxyflavones were chosen as model compounds. Human liver, C57 mouse liver and intestinal 59 fraction, as well as C57 intestinal perfusion model were used. In human and C57 mouse, all selected flavones were found to be glucuronidated with the highest rates at the 7-OH group. In contrast, flavones with 3-OH group were not sulfated at all. Both glucuronidation and sulfation preferred 4'- and 7-OH in human and mouse in vitro and in situ. There were differences in glucuronidation and sulfation in human and mouse observed for all flavones and it is based on substitutional positions of the hydroxyl groups. The S9 fractions could accurately model glucuronidation (as the slope of correlation curve was 0.7988 for those flavones with 4'- or 7-OH) and sulfation (as the slope of correlation curve was 0.9834) in situ. Conclusively, the sulfation and glucuronidation of the flavones was regiospecific- and speciesdependent. Sulfation and glucuronidation in the mouse intestine in vitro were correlated well with those in situ. (C) 2012 Elsevier Ltd. All rights reserved.