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Updated: Dec 14, 2025
Mouse Model of Oleic Acid-Induced Acute Respiratory Distress Syndrome
Published on: June 2, 2022
LC-MS-Based Metabolomic Study of Oleanolic Acid-Induced Hepatotoxicity in Mice
Hong Feng1, Ying-Qiu Wu1, Ya-Sha Xu1
1Key Laboratory of Basic Pharmacology of the Ministry of Education and Joint International Research Laboratory of Ethnomedicine of the Ministry of Education, Zunyi Medical University, Zunyi, China.
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.
Insights
Oleanolic acid (OA), a hepatoprotective drug, can cause liver toxicity. This study reveals that increased bile acids are the primary driver of OA-induced liver damage, offering new insights into its mechanism.
Area of Science:
- Pharmacology
- Toxicology
- Metabolomics
Background:
- Oleanolic acid (OA) is a widely used hepatoprotective agent in China with potential anti-tumor applications.
- However, OA can induce liver toxicity at higher doses or with prolonged use.
- Understanding the mechanism of OA-induced hepatotoxicity is crucial for its safe application.
Purpose of the Study:
- To investigate the underlying mechanism of oleanolic acid-induced hepatotoxicity.
- To analyze liver metabolic profiles to identify key pathways involved in OA toxicity.
- To provide a basis for further research on hepatotoxic drug mechanisms.
Main Methods:
- Untargeted ultrahigh performance liquid chromatography (UHPLC)-Q Exactive Orbitrap mass spectrometry (MS) was employed to obtain liver metabolic profiles.
- Targeted UHPLC-TSQ-MS was used to specifically verify alterations in bile acid metabolism.
- Comparative analysis of metabolic profiles from OA-treated and control groups.
Main Results:
- Altered bile acid, amino acid, and energy metabolism were identified as potential contributors to OA-induced hepatotoxicity.
- Bile acid metabolism was confirmed as a significantly affected pathway.
- Increased levels of conjugated bile acids were identified as the primary contributors to OA-induced liver toxicity.
Conclusions:
- Increased bile acids are a key factor in oleanolic acid-induced hepatotoxicity.
- This finding sheds light on the mechanism of OA liver toxicity and offers a reference for studying other hepatotoxic drugs.
- Further investigation into bile acid metabolism is warranted for a deeper understanding of OA's toxicological profile.
