期刊
TOXICOLOGY LETTERS
卷 333, 期 -, 页码 290-302出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2020.08.007
关键词
Triptolide; Transcriptomics; Metabolomics; Apoptosis; Acylcarnitine
类别
资金
- National Cancer Institute Intramural Research Program, Hebei Science and Technology Department in China [17392501D]
- National Science Foundation of China [81973469]
- Doctoral Scientific Research Start-up Foundation from Henan University of Chinese Medicine [RSBSJJ2018-13]
Triptolide, a major active component of Triptergium wilfordii Hook. f, is used in the treatment of autoimmune disease. However, triptolide is associated with severe adverse reactions, especially hepatotoxicity, which limits its clinical application. To examine the underlying mechanism of triptolide-induced liver injury, a combination of dose- and time-dependent toxic effects, RNA-seq and metabolomics were employed. Triptolide-induced toxicity occurred in a dose- and time-dependent manners and was characterized by apoptosis and not necroptosis. Transcriptomics profiles of the dose-dependent response to triptolide suggested that PI3K/AKT, MAPK, TNF alpha and p53 signaling pathways were the vital steps in triptolide-induced hepatocyte apoptosis. Metabolomics further revealed that glycerophospholipid, fatty acid, leukotriene, purine and pyrimidine metabolism were the major metabolic alterations after triptolide exposure. Finally, acylcarnitines were identified as potential biomarkers for the early detection of triptolide-induced liver injury.
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