Metabolic alterations in triptolide-induced acute hepatotoxicity
Jie Zhao1,2, Cen Xie2, Xiyan Mu1
1Hebei Medical University, School of Pharmaceutical Science, Shijiazhuang, Hebei, China.
Biomedical Chromatography : BMC
|May 26, 2018
Summary
Triptolide, used for autoimmune diseases, can cause liver damage. This study used metabolomics to reveal that triptolide disrupts multiple metabolic pathways, offering new insights into its hepatotoxicity mechanism.
Area of Science:
- Pharmacology
- Toxicology
- Metabolomics
Background:
- Triptolide from Tripterygium wilfordii Hook. F treats autoimmune diseases.
- Hepatotoxicity is a severe adverse effect of triptolide, with an unknown mechanism.
Purpose of the Study:
- To investigate the mechanism of triptolide-induced hepatotoxicity.
- To characterize metabolomic changes in serum and liver following triptolide administration.
Main Methods:
- LC/MS-based metabolomic analysis in mice.
- Serum biochemical and liver histological assessments.
- Multivariate data analysis for metabolic alterations.
Main Results:
- 30 significantly altered metabolites identified post-triptolide treatment.
- 29 metabolite abundances correlated with toxicity severity.
- Pathway analysis linked hepatotoxicity to disruptions in glutathione, TCA, purine, glycerophospholipid, taurine, pantothenate/CoA, pyrimidine, and amino acid metabolism.
Conclusions:
- Triptolide-induced hepatotoxicity involves significant alterations in multiple metabolic pathways.
- This study provides novel mechanistic insights into triptolide's liver toxicity.
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