Comprehensive analysis of transcriptomics and metabolomics to understand triptolide-induced liver injury in mice.
Toxicol Lett
; 333: 290-302, 2020 Oct 15.
Article
en En
| MEDLINE
| ID: mdl-32835833
ABSTRACT
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, TNFα 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fenantrenos
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Apoptosis
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Diterpenos
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Metaboloma
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Enfermedad Hepática Inducida por Sustancias y Drogas
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Transcriptoma
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Necroptosis
Tipo de estudio:
Screening_studies
Límite:
Animals
Idioma:
En
Revista:
Toxicol Lett
Año:
2020
Tipo del documento:
Article