Abstract

Bisphenol A (BPA) is an endocrine-disrupting chemical, and is predominantly metabolized into glucuronide in mammals. The present study was conducted in order to examine the hepatic and intestinal glucuronidation of BPA in humans and laboratory animals such as monkeys, dogs, rats, and mice in an in vitro system using microsomal fractions. K_m, V_max, and CL_int values in human liver microsomes were 7.54 µM, 17.7 nmol/min/mg protein, and 2.36 mL/min/mg protein, respectively. CL_int values in liver microsomes of monkey, dogs, rats, and mice were 1.5-, 2.4-, 1.7- and 8.2-fold that of humans, respectively. In intestinal microsomes, K_m, V_max, and CL_int values in humans were 39.3 µM, 0.65 nmol/min/mg protein, and 0.02 mL/min/mg protein, respectively. The relative levels of CL_int in monkey, dogs, rats, and mice to that of humans were 7.0-, 12-, 34-, and 29-fold, respectively. Although CL_int values were higher in liver microsomes than in intestinal microsomes in all species, and marked species difference in the ratio of liver to intestinal microsomes was observed as follows: humans, 118; monkeys, 25; dogs, 23; rats, 5.9; mice, 33. These results suggest that the functional roles of UDP-glucuronosyltransferase (UGT) enzymes expressed in the liver and intestines in the metabolism of BPA extensively differ among humans, monkeys, dogs, rats, and mice.

摘要

双酚 A (BPA) 是一种内分泌干扰化学物质，主要在哺乳动物体内代谢为葡萄糖苷酸。本研究旨在使用微粒体组分在体外系统中检查人类和实验动物（例如猴子、狗、大鼠和小鼠）中 BPA 的肝脏和肠道葡萄糖醛酸化。人肝微粒体中的K _m、V _max和CL _int值分别为 7.54 µM、17.7 nmol/min/mg 蛋白和 2.36 mL/min/mg 蛋白。猴、狗、大鼠和小鼠肝微粒体中的CL _{int值分别是人类的 1.5 倍、2.4 倍、1.7 倍和 8.2 倍。}在肠道微粒体中，K _m、V _max和CL _int在人体中的值分别为 39.3 µM、0.65 nmol/min/mg 蛋白质和 0.02 mL/min/mg 蛋白质。猴、狗、大鼠和小鼠中CL _int的相对水平是人类的 7.0 倍、12 倍、34 倍和 29 倍。虽然CL _int在所有物种中，肝微粒体中的值均高于肠道微粒体，并且观察到肝脏与肠道微粒体比率的显着物种差异如下：人类，118；猴子，25；狗，23；大鼠，5.9；小鼠，33。这些结果表明，在肝脏和肠道中表达的 UDP-葡萄糖醛酸基转移酶 (UGT) 酶在 BPA 代谢中的功能作用在人类、猴子、狗、大鼠和小鼠之间存在很大差异。