Species difference of metabolic clearance of bisphenol A using cryopreserved hepatocytes from rats, monkeys and humans

被引：34
|
作者：
Kurebayashi, Hideo [1 ]
Okudaira, Kazuho [2 ]
Ohno, Yasuo [1 ]
机构：
[1] Natl Inst Hlth Sci, Div Pharmacol, Setagaya Ku, Tokyo 1588501, Japan
[2] Toho Univ, Fac Pharmaceut Sci, Funabashi, Chiba 2748510, Japan
来源：
TOXICOLOGY LETTERS | 2010年 / 198卷 / 02期
关键词：
Bisphenol A; Hepatic clearance; Cryopreserved hepatocytes; Rat; Monkey; Human; IN-VITRO; XENOBIOTIC METABOLISM; PREDICTION; LIVER; TOXICOKINETICS; DISPOSITION; GLUCURONIDE; MICROSOMES; CHIMPANZEES; BINDING;
D O I：
10.1016/j.toxlet.2010.06.017
中图分类号：
R99 [毒物学（毒理学）];
学科分类号：
100405 ;
摘要：
In vitro metabolism of bisphenol A (BPA), an weak estrogen, was studied with cryopreserved hepatocytes from rat, monkey and human, and was compared with in vivo metabolism reported. The metabolites identified include a major metabolite. BPA glucuronide (BPAG) and BPA sulfate (BPAS). The metabolic rates of bisphenol A at 20 mu M by the hepatocytes (BPAG plus BPAS, nmol/10(6) cells/h) followed the order of rats (48 + 12) > monkeys (18 + 4) > humans (8.6 + 0.8), respectively. The rate of BPAG formation was much higher than that of BPAS formation in all these species. For the BPAG formation, we have determined the apparent K-m (mu M) of rats (3), monkeys (7), and humans (5). V-max (nmol/10(6) cells/h) in hepatocytes followed the order of rats (55) > monkeys (22) > humans (11). The total CLH for the hepatic formation of BPAG plus BPAS (L/h/kg BW) estimated by well-stirred model with low f(B) value followed the order of rats (3.0) > monkeys (0.68) > humans (0.27), correlating well with in vivo studies of BPA subcutaneously injected rats and monkeys. This study showed that the cryopreserved hepatocytes could be a useful tool for assessing BPA metabolism and predicting systemic exposure of BPA. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码：210 / 215
页数：6
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