Inoue H, Yokota H, Makino T, Yuasa A, Kato S
Department of Veterinary Physiology, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido, 069-8501 Japan.
Drug Metab Dispos. 2001 Aug;29(8):1084-7.
The environmental estrogen bisphenol A, orally introduced into the body, passes through the liver and modulates the endocrine system to elicit irreversible changes in the functioning of reproduction. To elucidate the actual and dynamic metabolism of bisphenol A in the liver before its arrival at target organs, this study evaluated the metabolism and disposition of the compound within the passage through the liver in Sprague-Dawley rats. On perfusion of 7.5 micromol of bisphenol A into the liver via the portal vein, approximately 91% of the infused bisphenol A was absorbed by the liver tissue, and about 65% of the absorbed bisphenol A was glucuronidated within 60 min. Roughly 65% of the bisphenol A glucuronide that formed in the liver was excreted into the bile and about 35% into the hepatic vein. On perfusion of 0.01, 0.05, and 0.1 mM bisphenol A solution into the liver, free bisphenol A was excreted only into the vein at 5.6, 9.3, and 14.6%, respectively, of the total bisphenol A. These results suggest that most bisphenol A absorbed by the intestine is probably glucuronidated exclusively in the liver and the conjugate is excreted mainly into the bile.
环境雌激素双酚A经口服进入人体后,会通过肝脏并调节内分泌系统,从而引发生殖功能的不可逆变化。为了阐明双酚A在到达靶器官之前在肝脏中的实际动态代谢情况,本研究评估了该化合物在Sprague-Dawley大鼠肝脏中的代谢及处置过程。通过门静脉向肝脏灌注7.5微摩尔双酚A后,约91%注入的双酚A被肝脏组织吸收,且约65%被吸收的双酚A在60分钟内发生葡萄糖醛酸化。肝脏中形成的双酚A葡萄糖醛酸酯约65%排入胆汁,约35%进入肝静脉。向肝脏灌注0.01、0.05和0.1 mM双酚A溶液时,游离双酚A仅分别以总双酚A的5.6%、9.3%和14.6%排泄到静脉中。这些结果表明,肠道吸收的大部分双酚A可能仅在肝脏中发生葡萄糖醛酸化,且结合物主要排入胆汁。