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LC-MS-Based Metabolomic Study of Oleanolic Acid-Induced Hepatotoxicity in Mice

Oleanolic acid (OA), a natural triterpenoid, which has the development prospects in anti-tumor therapy is a widely used hepatoprotective drug in China. It has been reported that OA can cause liver toxicity after higher doses or longer-term use. Therefore, the study aims to explore the possible hepat...

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Autores principales: Feng, Hong, Wu, Ying-Qiu, Xu, Ya-Sha, Wang, Ke-Xin, Qin, Xue-Mei, Lu, Yuan-Fu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326119/
https://www.ncbi.nlm.nih.gov/pubmed/32670053
http://dx.doi.org/10.3389/fphar.2020.00747
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author Feng, Hong
Wu, Ying-Qiu
Xu, Ya-Sha
Wang, Ke-Xin
Qin, Xue-Mei
Lu, Yuan-Fu
author_facet Feng, Hong
Wu, Ying-Qiu
Xu, Ya-Sha
Wang, Ke-Xin
Qin, Xue-Mei
Lu, Yuan-Fu
author_sort Feng, Hong
collection PubMed
description Oleanolic acid (OA), a natural triterpenoid, which has the development prospects in anti-tumor therapy is a widely used hepatoprotective drug in China. It has been reported that OA can cause liver toxicity after higher doses or longer-term use. Therefore, the study aims to explore the possible hepatotoxicity mechanism based on liver metabolic profiles. Liver metabolic profiles were obtained from untargeted ultrahigh performance liquid chromatography (UHPLC)-Q Exactive Orbitrap mass spectrometry (MS) technique. It was found that altered bile acid, amino acid, and energy metabolism might be at least partly responsible for OA-induced hepatotoxicity. Bile acid metabolism, as the most important pathway, was verified by using UHPLC-TSQ-MS, indicating that conjugated bile acids were the main contributors to OA-induced liver toxicity. Our findings confirmed that increased bile acids were the key element of OA hepatotoxicity, which may open new insights for OA hepatotoxicity in-depth investigations, as well as provide a reference basis for more hepatotoxic drug mechanism research.
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spelling pubmed-73261192020-07-14 LC-MS-Based Metabolomic Study of Oleanolic Acid-Induced Hepatotoxicity in Mice Feng, Hong Wu, Ying-Qiu Xu, Ya-Sha Wang, Ke-Xin Qin, Xue-Mei Lu, Yuan-Fu Front Pharmacol Pharmacology Oleanolic acid (OA), a natural triterpenoid, which has the development prospects in anti-tumor therapy is a widely used hepatoprotective drug in China. It has been reported that OA can cause liver toxicity after higher doses or longer-term use. Therefore, the study aims to explore the possible hepatotoxicity mechanism based on liver metabolic profiles. Liver metabolic profiles were obtained from untargeted ultrahigh performance liquid chromatography (UHPLC)-Q Exactive Orbitrap mass spectrometry (MS) technique. It was found that altered bile acid, amino acid, and energy metabolism might be at least partly responsible for OA-induced hepatotoxicity. Bile acid metabolism, as the most important pathway, was verified by using UHPLC-TSQ-MS, indicating that conjugated bile acids were the main contributors to OA-induced liver toxicity. Our findings confirmed that increased bile acids were the key element of OA hepatotoxicity, which may open new insights for OA hepatotoxicity in-depth investigations, as well as provide a reference basis for more hepatotoxic drug mechanism research. Frontiers Media S.A. 2020-05-26 /pmc/articles/PMC7326119/ /pubmed/32670053 http://dx.doi.org/10.3389/fphar.2020.00747 Text en Copyright © 2020 Feng, Wu, Xu, Wang, Qin and Lu http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Feng, Hong
Wu, Ying-Qiu
Xu, Ya-Sha
Wang, Ke-Xin
Qin, Xue-Mei
Lu, Yuan-Fu
LC-MS-Based Metabolomic Study of Oleanolic Acid-Induced Hepatotoxicity in Mice
title LC-MS-Based Metabolomic Study of Oleanolic Acid-Induced Hepatotoxicity in Mice
title_full LC-MS-Based Metabolomic Study of Oleanolic Acid-Induced Hepatotoxicity in Mice
title_fullStr LC-MS-Based Metabolomic Study of Oleanolic Acid-Induced Hepatotoxicity in Mice
title_full_unstemmed LC-MS-Based Metabolomic Study of Oleanolic Acid-Induced Hepatotoxicity in Mice
title_short LC-MS-Based Metabolomic Study of Oleanolic Acid-Induced Hepatotoxicity in Mice
title_sort lc-ms-based metabolomic study of oleanolic acid-induced hepatotoxicity in mice
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326119/
https://www.ncbi.nlm.nih.gov/pubmed/32670053
http://dx.doi.org/10.3389/fphar.2020.00747
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