Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1783716823499276288 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8248983 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT tuyifan hepatoentericrecyclingisanewdispositionmechanismfororallyadministeredphenolicdrugsandphytochemicalsinrats AT wanglu hepatoentericrecyclingisanewdispositionmechanismfororallyadministeredphenolicdrugsandphytochemicalsinrats AT rongyi hepatoentericrecyclingisanewdispositionmechanismfororallyadministeredphenolicdrugsandphytochemicalsinrats AT tamvincent hepatoentericrecyclingisanewdispositionmechanismfororallyadministeredphenolicdrugsandphytochemicalsinrats AT yintaijun hepatoentericrecyclingisanewdispositionmechanismfororallyadministeredphenolicdrugsandphytochemicalsinrats AT gaosong hepatoentericrecyclingisanewdispositionmechanismfororallyadministeredphenolicdrugsandphytochemicalsinrats AT singhrashim hepatoentericrecyclingisanewdispositionmechanismfororallyadministeredphenolicdrugsandphytochemicalsinrats AT huming hepatoentericrecyclingisanewdispositionmechanismfororallyadministeredphenolicdrugsandphytochemicalsinrats |