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

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 disposi...

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Autores principales: Tu, Yifan, Wang, Lu, Rong, Yi, Tam, Vincent, Yin, Taijun, Gao, Song, Singh, Rashim, Hu, Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248983/
https://www.ncbi.nlm.nih.gov/pubmed/34196607
http://dx.doi.org/10.7554/eLife.58820
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author Tu, Yifan
Wang, Lu
Rong, Yi
Tam, Vincent
Yin, Taijun
Gao, Song
Singh, Rashim
Hu, Ming
author_facet Tu, Yifan
Wang, Lu
Rong, Yi
Tam, Vincent
Yin, Taijun
Gao, Song
Singh, Rashim
Hu, Ming
author_sort Tu, Yifan
collection PubMed
description 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.
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spelling pubmed-82489832021-07-02 Hepatoenteric recycling is a new disposition mechanism for orally administered phenolic drugs and phytochemicals in rats Tu, Yifan Wang, Lu Rong, Yi Tam, Vincent Yin, Taijun Gao, Song Singh, Rashim Hu, Ming eLife Medicine 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. eLife Sciences Publications, Ltd 2021-07-01 /pmc/articles/PMC8248983/ /pubmed/34196607 http://dx.doi.org/10.7554/eLife.58820 Text en © 2021, Tu et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Medicine
Tu, Yifan
Wang, Lu
Rong, Yi
Tam, Vincent
Yin, Taijun
Gao, Song
Singh, Rashim
Hu, Ming
Hepatoenteric recycling is a new disposition mechanism for orally administered phenolic drugs and phytochemicals in rats
title Hepatoenteric recycling is a new disposition mechanism for orally administered phenolic drugs and phytochemicals in rats
title_full Hepatoenteric recycling is a new disposition mechanism for orally administered phenolic drugs and phytochemicals in rats
title_fullStr Hepatoenteric recycling is a new disposition mechanism for orally administered phenolic drugs and phytochemicals in rats
title_full_unstemmed Hepatoenteric recycling is a new disposition mechanism for orally administered phenolic drugs and phytochemicals in rats
title_short Hepatoenteric recycling is a new disposition mechanism for orally administered phenolic drugs and phytochemicals in rats
title_sort hepatoenteric recycling is a new disposition mechanism for orally administered phenolic drugs and phytochemicals in rats
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248983/
https://www.ncbi.nlm.nih.gov/pubmed/34196607
http://dx.doi.org/10.7554/eLife.58820
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