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LC-MS-Based Metabolomic Study of Oleanolic Acid-Induced Hepatotoxicity in Mice
- Source :
- Frontiers in Pharmacology, Vol 11 (2020)
- Publication Year :
- 2020
- Publisher :
- Frontiers Media S.A., 2020.
-
Abstract
- 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.
Details
- Language :
- English
- ISSN :
- 16639812
- Volume :
- 11
- Database :
- Directory of Open Access Journals
- Journal :
- Frontiers in Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.3ff80e86a0f84b34b57c0c26f6c3ac55
- Document Type :
- article
- Full Text :
- https://doi.org/10.3389/fphar.2020.00747