Disposition of naringenin via glucuronidation pathway is affected by compensating efflux transporters of hydrophilic glucuronides.
Disposition of naringenin via glucuronidation pathway is affected by compensating efflux transporters of hydrophilic glucuronides.
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DOI：
10.1021/mp900013d
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发表时间：
2009-11
影响因子：
4.9
通讯作者：
Hu M
中科院分区：
文献类型：
--
作者：
Xu H;Kulkarni KH;Singh R;Yang Z;Wang SW;Tam VH;Hu M
本研究的目的是探讨如何外排转运蛋白和UDP-葡萄糖醛酸转移酶（UGT）影响的处置柚皮素。采用沿着大鼠肠和肝微粒体，采用胆管插管大鼠肠灌注模型。在肠灌流模型中，柚皮素代谢产物的吸收和随后的排泄都是快速的和部位依赖性的（p < 0.05）。柚皮素在结肠吸收最多，其葡萄糖醛酸苷在十二指肠排泄最多。在代谢研究中，柚皮素葡萄糖醛酸化的固有清除率值在空肠微粒体中最高，其次是肝脏、回肠和结肠微粒体。然而，在大鼠灌注模型中，微粒体中的快速代谢并不总是转化为更有效的排泄，因为存在限速外排转运蛋白。当单独使用时，MK-571（多药耐药相关蛋白2或Mrp 2的抑制剂）或潘生丁（乳腺癌耐药蛋白或Bcrp 1的抑制剂）不影响柚皮素葡萄糖醛酸苷的排泄，但当联合使用时，它们显著（p < 0.05）降低了柚皮素葡萄糖醛酸苷的肠道和胆汁排泄。总之，外排转运蛋白Mrp 2和Bcrp 1显示出相互补偿并使类黄酮的肠排泄（即，柚皮素）葡糖苷酸。
The purposes of this study were to investigate how efflux transporters and UDP-glucuronosyltransferases (UGT) affect the disposition of naringenin. A rat intestinal perfusion model with bile duct cannulation was used along with rat intestinal and liver microsomes. In the intestinal perfusion model, both absorption and subsequent excretion of naringenin metabolites were rapid and site-dependent (p < 0.05). Naringenin was absorbed the most in colon and its glucuronides were excreted the most in duodenum. In metabolism studies, the intrinsic clearance value of naringenin glucuronidation was the highest in jejunum microsomes, followed by liver, ileal and colonic microsomes. The rapid metabolism in microsomes did not always translate into more efficient excretion in the rat perfusion model, however, because of presence of rate-limiting efflux transporters. When used separately, MK-571 (an inhibitor of multidrug resistance-related protein 2 or Mrp2) or dipyridamole (an inhibitor of breast cancer resistance protein or Bcrp1) did not affect excretion of naringenin glucuronides, but when used together, they significantly (p < 0.05) decreased intestinal and biliary excretion of naringenin glucuronides. In conclusion, efflux transporters Mrp2 and Bcrp1 are shown to compensate for each other and enable the intestinal excretion of flavonoid (i.e., naringenin) glucuronides.
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影响因子：
3.5
作者：
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通讯作者：
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DOI：
10.1152/ajpgi.1999.277.1.g120
发表时间：
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DOI：
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发表时间：
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影响因子：
3.5
作者：
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影响因子：
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作者：
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通讯作者：
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