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Comprehensive analysis of transcriptomics and metabolomics to understand triptolide-induced liver injury in mice

文献类型：期刊论文

作者Zhao, Jie1,2,3,4; Xie, Cen4,6; Wang, Kanglong6; Takahashi, Shogo4; Krausz, Kristopher W.4; Lu, Dasheng4; Wang, Qiong4; Luo, Yuhong4; Gong, Xianqiong4; Mu, Xiyan3
刊名TOXICOLOGY LETTERS
出版日期2020-10-15
卷号333页码:290-302
关键词Triptolide Transcriptomics Metabolomics Apoptosis Acylcarnitine
ISSN号0378-4274
DOI10.1016/j.toxlet.2020.08.007
通讯作者Wang, Qiao(qiaowang88@hotmail.com) ; Su, Suwen(suswmk@hebmu.edu.cn)
英文摘要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.
WOS关键词INDUCED HEPATOTOXICITY ; ACETAMINOPHEN TOXICITY ; PATHWAY ; ACYLCARNITINES ; INHIBITION ; MECHANISMS ; APOPTOSIS ; PI3K/AKT ; RATS
资助项目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]
WOS研究方向Toxicology
语种英语
WOS记录号WOS:000579907000031
出版者ELSEVIER IRELAND LTD
源URL[http://119.78.100.183/handle/2S10ELR8/291376]  
专题新药研究国家重点实验室
通讯作者Wang, Qiao; Su, Suwen
作者单位1.Henan Univ Chinese Med, Henan Key Lab Chinese Med Resp Dis, Collaborat Innovat Ctr Resp Dis Diag & Treatment, Zhengzhou, Henan, Peoples R China
2.Henan Univ Chinese Med, Acad Chinses Med Sci, Chinese Med Dev Henan Prov, Zhengsshou, Henan, Peoples R China
3.Hebei Med Univ, Sch Pharmaceut Sci, Shijiazhuang, Hebei, Peoples R China
4.NCI, Lab Metab, Bethesda, MD USA
5.Hebei Med Univ, Dept Pharmacol, Shijiazhuang, Hebei, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Zhao, Jie,Xie, Cen,Wang, Kanglong,et al. Comprehensive analysis of transcriptomics and metabolomics to understand triptolide-induced liver injury in mice[J]. TOXICOLOGY LETTERS,2020,333:290-302.
APA Zhao, Jie.,Xie, Cen.,Wang, Kanglong.,Takahashi, Shogo.,Krausz, Kristopher W..,...&Gonzalez, Frank J..(2020).Comprehensive analysis of transcriptomics and metabolomics to understand triptolide-induced liver injury in mice.TOXICOLOGY LETTERS,333,290-302.
MLA Zhao, Jie,et al."Comprehensive analysis of transcriptomics and metabolomics to understand triptolide-induced liver injury in mice".TOXICOLOGY LETTERS 333(2020):290-302.

入库方式： OAI收割

来源：上海药物研究所

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