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UPLC-Q-TOF/MS Based Metabolomics Approach to Study the Hepatotoxicity of Cantharidin on Mice
- Source :
- Chemical Research in Toxicology. 32:2204-2213
- Publication Year :
- 2019
- Publisher :
- American Chemical Society (ACS), 2019.
-
Abstract
- Cantharidin is the major bioactive compound extracted from the blister beetle, a traditional Chinese medicine, and has been proved to be a natural component with widely antitumor activity. However, clinical application of cantharidin is relatively restricted due to its potential toxic effects, especially hepatotoxicity. Although cantharidin-induced liver injury has been reported, the underlying molecular mechanisms remain unclear. In the present study, an UPLC-Q-TOF/MS based metabolomics approach combined with blood biochemical analysis, histopathological examination, and cell apoptosis assay were used to investigate the mechanisms of cantharidin-induced hepatotoxicity. A total of 54 significantly changed metabolites and 14 disturbed metabolic pathways were identified in the cantharidin exposed groups. Among them, four metabolites (oxidized glutathione, glutathione, 3-sulfinoalanine, and deoxycholic acid 3-glucuronide) were selected based on their high impact value and potential biological function in the process of liver injury post cantharidin treatment. Our study provides a deeper understanding of the mechanisms of cantharidin-induced hepatotoxicity and may contribute to reduce the liver injury and gain more effective and safe clinical use of cantharidin. In addition, our results also demonstrated that cantharidin could impair multiple biological processes in liver, and future studies will be necessary to reveal the detailed molecular mechanisms of cantharidin-induced hepatotoxicity.
- Subjects :
- Male
Blister beetle
Antineoplastic Agents
Apoptosis
Traditional Chinese medicine
010501 environmental sciences
Pharmacology
Toxicology
01 natural sciences
Mass Spectrometry
Cell Line
Mice
03 medical and health sciences
chemistry.chemical_compound
Metabolomics
medicine
Animals
Humans
Chromatography, High Pressure Liquid
030304 developmental biology
0105 earth and related environmental sciences
Liver injury
0303 health sciences
Cantharidin
biology
Deoxycholic acid
General Medicine
Glutathione
medicine.disease
biology.organism_classification
Bioactive compound
Liver
chemistry
Chemical and Drug Induced Liver Injury
Subjects
Details
- ISSN :
- 15205010 and 0893228X
- Volume :
- 32
- Database :
- OpenAIRE
- Journal :
- Chemical Research in Toxicology
- Accession number :
- edsair.doi.dedup.....72c0d1be7961a096602b79dfe2242654