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A Major Intestinal Catabolite of Quercetin Glycosides, 3-Hydroxyphenylacetic Acid, Protects the Hepatocytes from the Acetaldehyde-Induced Cytotoxicity through the Enhancement of the Total Aldehyde Dehydrogenase Activity

Aldehyde dehydrogenases (ALDHs) are the major enzyme superfamily for the aldehyde metabolism. Since the ALDH polymorphism leads to the accumulation of acetaldehyde, we considered that the enhancement of the liver ALDH activity by certain food ingredients could help prevent alcohol-induced chronic di...

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Autores principales: Liu, Yujia, Myojin, Takumi, Li, Kexin, Kurita, Ayuki, Seto, Masayuki, Motoyama, Ayano, Liu, Xiaoyang, Satoh, Ayano, Munemasa, Shintaro, Murata, Yoshiyuki, Nakamura, Toshiyuki, Nakamura, Yoshimasa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8836260/
https://www.ncbi.nlm.nih.gov/pubmed/35163684
http://dx.doi.org/10.3390/ijms23031762
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author Liu, Yujia
Myojin, Takumi
Li, Kexin
Kurita, Ayuki
Seto, Masayuki
Motoyama, Ayano
Liu, Xiaoyang
Satoh, Ayano
Munemasa, Shintaro
Murata, Yoshiyuki
Nakamura, Toshiyuki
Nakamura, Yoshimasa
author_facet Liu, Yujia
Myojin, Takumi
Li, Kexin
Kurita, Ayuki
Seto, Masayuki
Motoyama, Ayano
Liu, Xiaoyang
Satoh, Ayano
Munemasa, Shintaro
Murata, Yoshiyuki
Nakamura, Toshiyuki
Nakamura, Yoshimasa
author_sort Liu, Yujia
collection PubMed
description Aldehyde dehydrogenases (ALDHs) are the major enzyme superfamily for the aldehyde metabolism. Since the ALDH polymorphism leads to the accumulation of acetaldehyde, we considered that the enhancement of the liver ALDH activity by certain food ingredients could help prevent alcohol-induced chronic diseases. Here, we evaluated the modulating effects of 3-hydroxyphenylacetic acid (OPAC), the major metabolite of quercetin glycosides, on the ALDH activity and acetaldehyde-induced cytotoxicity in the cultured cell models. OPAC significantly enhanced the total ALDH activity not only in mouse hepatoma Hepa1c1c7 cells, but also in human hepatoma HepG2 cells. OPAC significantly increased not only the nuclear level of aryl hydrocarbon receptor (AhR), but also the AhR-dependent reporter gene expression, though not the nuclear factor erythroid-2-related factor 2 (Nrf2)-dependent one. The pretreatment of OPAC at the concentration required for the ALDH upregulation completely inhibited the acetaldehyde-induced cytotoxicity. Silencing AhR impaired the resistant effect of OPAC against acetaldehyde. These results strongly suggested that OPAC protects the cells from the acetaldehyde-induced cytotoxicity, mainly through the AhR-dependent and Nrf2-independent enhancement of the total ALDH activity. Our findings suggest that OPAC has a protective potential in hepatocyte models and could offer a new preventive possibility of quercetin glycosides for targeting alcohol-induced chronic diseases.
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spelling pubmed-88362602022-02-12 A Major Intestinal Catabolite of Quercetin Glycosides, 3-Hydroxyphenylacetic Acid, Protects the Hepatocytes from the Acetaldehyde-Induced Cytotoxicity through the Enhancement of the Total Aldehyde Dehydrogenase Activity Liu, Yujia Myojin, Takumi Li, Kexin Kurita, Ayuki Seto, Masayuki Motoyama, Ayano Liu, Xiaoyang Satoh, Ayano Munemasa, Shintaro Murata, Yoshiyuki Nakamura, Toshiyuki Nakamura, Yoshimasa Int J Mol Sci Article Aldehyde dehydrogenases (ALDHs) are the major enzyme superfamily for the aldehyde metabolism. Since the ALDH polymorphism leads to the accumulation of acetaldehyde, we considered that the enhancement of the liver ALDH activity by certain food ingredients could help prevent alcohol-induced chronic diseases. Here, we evaluated the modulating effects of 3-hydroxyphenylacetic acid (OPAC), the major metabolite of quercetin glycosides, on the ALDH activity and acetaldehyde-induced cytotoxicity in the cultured cell models. OPAC significantly enhanced the total ALDH activity not only in mouse hepatoma Hepa1c1c7 cells, but also in human hepatoma HepG2 cells. OPAC significantly increased not only the nuclear level of aryl hydrocarbon receptor (AhR), but also the AhR-dependent reporter gene expression, though not the nuclear factor erythroid-2-related factor 2 (Nrf2)-dependent one. The pretreatment of OPAC at the concentration required for the ALDH upregulation completely inhibited the acetaldehyde-induced cytotoxicity. Silencing AhR impaired the resistant effect of OPAC against acetaldehyde. These results strongly suggested that OPAC protects the cells from the acetaldehyde-induced cytotoxicity, mainly through the AhR-dependent and Nrf2-independent enhancement of the total ALDH activity. Our findings suggest that OPAC has a protective potential in hepatocyte models and could offer a new preventive possibility of quercetin glycosides for targeting alcohol-induced chronic diseases. MDPI 2022-02-03 /pmc/articles/PMC8836260/ /pubmed/35163684 http://dx.doi.org/10.3390/ijms23031762 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Liu, Yujia
Myojin, Takumi
Li, Kexin
Kurita, Ayuki
Seto, Masayuki
Motoyama, Ayano
Liu, Xiaoyang
Satoh, Ayano
Munemasa, Shintaro
Murata, Yoshiyuki
Nakamura, Toshiyuki
Nakamura, Yoshimasa
A Major Intestinal Catabolite of Quercetin Glycosides, 3-Hydroxyphenylacetic Acid, Protects the Hepatocytes from the Acetaldehyde-Induced Cytotoxicity through the Enhancement of the Total Aldehyde Dehydrogenase Activity
title A Major Intestinal Catabolite of Quercetin Glycosides, 3-Hydroxyphenylacetic Acid, Protects the Hepatocytes from the Acetaldehyde-Induced Cytotoxicity through the Enhancement of the Total Aldehyde Dehydrogenase Activity
title_full A Major Intestinal Catabolite of Quercetin Glycosides, 3-Hydroxyphenylacetic Acid, Protects the Hepatocytes from the Acetaldehyde-Induced Cytotoxicity through the Enhancement of the Total Aldehyde Dehydrogenase Activity
title_fullStr A Major Intestinal Catabolite of Quercetin Glycosides, 3-Hydroxyphenylacetic Acid, Protects the Hepatocytes from the Acetaldehyde-Induced Cytotoxicity through the Enhancement of the Total Aldehyde Dehydrogenase Activity
title_full_unstemmed A Major Intestinal Catabolite of Quercetin Glycosides, 3-Hydroxyphenylacetic Acid, Protects the Hepatocytes from the Acetaldehyde-Induced Cytotoxicity through the Enhancement of the Total Aldehyde Dehydrogenase Activity
title_short A Major Intestinal Catabolite of Quercetin Glycosides, 3-Hydroxyphenylacetic Acid, Protects the Hepatocytes from the Acetaldehyde-Induced Cytotoxicity through the Enhancement of the Total Aldehyde Dehydrogenase Activity
title_sort major intestinal catabolite of quercetin glycosides, 3-hydroxyphenylacetic acid, protects the hepatocytes from the acetaldehyde-induced cytotoxicity through the enhancement of the total aldehyde dehydrogenase activity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8836260/
https://www.ncbi.nlm.nih.gov/pubmed/35163684
http://dx.doi.org/10.3390/ijms23031762
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