Department of Health Pharmacy, Yokohama University of Pharmacy, Yokohama, Japan.
Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Drug Chem Toxicol. 2022 Jul;45(4):1565-1569. doi: 10.1080/01480545.2020.1847133. Epub 2020 Nov 13.
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 system using microsomal fractions. , , and values in human liver microsomes were 7.54 µM, 17.7 nmol/min/mg protein, and 2.36 mL/min/mg protein, respectively. 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, , , and 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 in monkey, dogs, rats, and mice to that of humans were 7.0-, 12-, 34-, and 29-fold, respectively. Although 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.
双酚 A(BPA)是一种内分泌干扰化学物质,在哺乳动物中主要代谢为葡萄糖醛酸苷。本研究旨在使用微粒体部分在 系统中检查人以及猴、犬、大鼠和小鼠等实验动物的肝和肠内 BPA 的葡萄糖醛酸化。人肝微粒体中的 、 和 值分别为 7.54 μM、17.7 nmol/min/mg 蛋白和 2.36 mL/min/mg 蛋白。猴、犬、大鼠和小鼠肝微粒体中的 值分别为人的 1.5、2.4、1.7 和 8.2 倍。在肠微粒体中,人肝微粒体中的 、 和 值分别为 39.3 μM、0.65 nmol/min/mg 蛋白和 0.02 mL/min/mg 蛋白。猴、犬、大鼠和小鼠相对于人的 值分别为 7.0、12、34 和 29 倍。尽管在所有物种中,肝微粒体中的 值均高于肠微粒体,而且还观察到肝与肠微粒体之间的比值存在明显的物种差异,其顺序如下:人,118;猴,25;犬,23;大鼠,5.9;小鼠,33。这些结果表明,在人类、猴、犬、大鼠和小鼠中,肝脏和肠道中表达的 UDP-葡糖醛酸基转移酶(UGT)酶在 BPA 代谢中的功能作用存在广泛差异。