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肝肠循环是口服给予的酚类药物和植物化学物质在大鼠体内的一种新的处置机制。

Hepatoenteric recycling is a new disposition mechanism for orally administered phenolic drugs and phytochemicals in rats.

机构信息

Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, United States.

Department of Pharmaceutical Sciences, College of Pharmacy, Texas Southern University, Houston, United States.

出版信息

Elife. 2021 Jul 1;10:e58820. doi: 10.7554/eLife.58820.

DOI:10.7554/eLife.58820
PMID:34196607
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8248983/
Abstract

Many orally administered phenolic drugs undergo enterohepatic recycling (EHR), presumably mediated by the hepatic phase II enzymes. However, the disposition of extrahepatically generated phase II metabolites is unclear. This paper aims to determine the new roles of liver and intestine in the disposition of oral phenolics. Sixteen representative phenolics were tested using direct portal vein infusion and/or intestinal perfusion. The results showed that certain glucuronides were efficiently recycled by liver. OATP1B1/1B3/2B1 were the responsible uptake transporters. Hepatic uptake is the rate-limiting step in hepatic recycling. Our findings showed that the disposition of many oral phenolics is mediated by intestinal glucuronidation and hepatic recycling. A new disposition mechanism 'Hepatoenteric Recycling (HER)", where intestine is the metabolic organ and liver is the recycling organ, was revealed. Further investigations focusing on HER should help interpret how intestinal aliments or co-administered drugs that alter gut enzymes (e.g. UGTs) expression/activities will impact the disposition of phenolics.

摘要

许多口服的酚类药物经历肠肝循环（EHR），推测是由肝的 II 相酶介导的。然而，肝外生成的 II 相代谢物的处置尚不清楚。本文旨在确定肝和肠在口服酚类药物处置中的新作用。使用直接门静脉输注和/或肠灌注测试了 16 种代表性酚类药物。结果表明，某些葡萄糖醛酸苷可被肝脏有效回收。OATP1B1/1B3/2B1 是负责摄取的转运体。肝摄取是肝内循环的限速步骤。我们的研究结果表明，许多口服酚类药物的处置是由肠道葡萄糖醛酸化和肝内循环介导的。揭示了一种新的处置机制“肝肠循环（HER）”，其中肠道是代谢器官，肝脏是回收器官。进一步的研究集中在 HER 上，应该有助于解释肠道营养品或共同给予的改变肠道酶（如 UGTs）表达/活性的药物将如何影响酚类药物的处置。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb2/8248983/4fdddd80544e/elife-58820-fig6.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb2/8248983/782b8a16891d/elife-58820-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb2/8248983/a0442e82d5a4/elife-58820-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb2/8248983/5b8a368e267a/elife-58820-fig4-figsupp1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb2/8248983/21d37353b96b/elife-58820-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb2/8248983/4fdddd80544e/elife-58820-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb2/8248983/ff9c6c19b011/elife-58820-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb2/8248983/a9911c6d8691/elife-58820-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb2/8248983/49e29bf83064/elife-58820-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb2/8248983/a5a3f919eab8/elife-58820-fig2-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb2/8248983/1f18c1e37580/elife-58820-fig2-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb2/8248983/782b8a16891d/elife-58820-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb2/8248983/a0442e82d5a4/elife-58820-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb2/8248983/5b8a368e267a/elife-58820-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb2/8248983/88dc50b222aa/elife-58820-fig4-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb2/8248983/a7e95bbccce9/elife-58820-fig4-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb2/8248983/21d37353b96b/elife-58820-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb2/8248983/4fdddd80544e/elife-58820-fig6.jpg

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