Intestinal uptake and biliary excretion of the isoflavone genistein in rats
Intestinal uptake and biliary excretion of the isoflavone genistein in rats
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DOI：
10.1093/jn/127.7.1260
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发表时间：
1997-07-01
影响因子：
4.2
通讯作者：
Barnes, S
中科院分区：
文献类型：
--
作者：
Sfakianos, J;Coward, L;Barnes, S
染料木黄酮是一种有效的特异性蛋白酪氨酸激酶抑制剂，天然存在于上述食物中，研究人员在麻醉的成年雌性大鼠中检测了染料木黄酮的肠道吸收、胆道排泄和代谢。4- c -14-染料木黄酮注入十二指肠后，迅速从肠道吸收，被肝脏吸收，并以7- o - β -葡萄糖醛酸盐缀合物的形式排泄到胆汁中。在4小时内，胆汁中c -14放射性的累积恢复为剂量的70-75%，当染料木素注入门静脉时，它也被肝脏有效吸收，与葡萄糖醛酸结合并转运到胆汁中，但十二指肠输注染料木素后收集的门静脉血中大部分含有染料木素7- o - β -葡萄糖醛酸，表明体内葡萄糖醛酸化发生在肠壁而不是肝脏。使用膨出的肠囊制剂证实了这一点。将染料木黄酮7- o - β -葡萄糖醛酸再输注到十二指肠或中小肠导致其在胆汁中重新出现，尽管比输注染料木黄酮时要慢。在4小时的收集期内，胆汁中c -14放射性的累积回收率分别为十二指肠输注和回肠输注给药剂量的27%和70-75%。这些数据表明染料木素在大鼠体内具有很高的生物利用度，并且由于其肠肝循环可能在胃肠道内积累。
The intestinal absorption, biliary excretion and metabolism of genistein, a potent and specific protein tyrosine kinase inhibitor that occurs naturally in say foods, was examined in anesthetized, adult female rats fitted with indwelling biliary cannulas, 4-C-14-Genistein, when infused into the duodenum, was rapidly absorbed from the intestine, taken up by the liver and excreted into the bile as its 7-O-beta-glucuronide conjugate. Cumulative recovery of C-14-radioactivity in the bile over a 4-h period was 70-75% of the dose, When genistein was infused into the portal vein, it was also taken up efficiently by the liver, conjugated with glucuronic acid and transported into bile, However, portal blood collected after duodenal infusions of genistein contained mostly genistein 7-O-beta-glucuronide, suggesting that in vivo glucuronidation occurred in the intestinal wall rather than the liver, This was confirmed using everted intestinal sac preparations. Reinfusion of genistein 7-O-beta-glucuronide into the duodenum or into the mid small intestine resulted in its reappearance in the bile, albeit more slowly than when genistein was infused. Over a 4-h collection period, the cumulative recovery of C-14-radioactivity in bile was 27 and 70-75% of the administered dose for duodenal and ileal infusions, respectively, These data indicate that genistein is highly bioavailable in rats and because of its enterohepatic circulation may accumulate within the gastrointestinal tract.