The Protective Roles of PPAR alpha Activation in Triptolide-Induced Liver Injury
Hu, Dan-Dan1,2,3; Zhao, Qi1; Cheng, Yan1; Xiao, Xue-Rong1; Huang, Jian-Feng1; Qu, Yan1; Li, Xian2,3; Tang, Ying-Mei4; Bao, Wei-Min5; Yang, Jin-Hui4; Jiang, Tao4; Hu, Jia-Peng6; Gonzalez, Frank J.7; Li, Fei1
Corresponding AuthorTang, Ying-Mei(tangyingmei_med@163.com) ; Li, Fei(lifeib@mail.kib.ac.cn)
2019-09-01
Source PublicationTOXICOLOGICAL SCIENCES
ISSN1096-6080
Volume171Issue:1Pages:1-12
AbstractTriptolide (TP), one of the main active ingredients in Tripterygium wilfordii Hook F, is clinically used to treat immune diseases but is known to cause liver injury. The aim of this study was to investigate the biomarkers for TP-induced hepatotoxicity in mice and to determine potential mechanisms of its liver injury. LC/MS-based metabolomics was used to determine the metabolites that were changed in TP-induced liver injury. The accumulation of long-chain acylcarnitines in serum indicated that TP exposure disrupted endogenous peroxisome proliferator-activated receptor alpha (PPAR alpha) signaling. Triptolide-induced liver injury could be alleviated by treatment of mice with the PPAR alpha agonist fenofibrate, whereas the PPAR alpha antagonist GW6471 increased hepatotoxicity. Furthermore, fenofibrate did not protect Ppara-/- mice from TP-induced liver injury, suggesting an essential role for the PPAR alpha in the protective effect of fenofibrate. Elevated long-chain acylcarnitines may protect TP-induced liver injury through activation of the NOTCH-NRF2 pathway as revealed in primary mouse hepatocytes and in vivo. In agreement with these observations in mice, the increase in long-chain acylcarnitines was observed in the serum of patients with cholestatic liver injury compared with healthy volunteers. These data demonstrated the role of PPAR alpha and long-chain acylcarnitines in TP-induced hepatotoxicity, and suggested that modulation of PPAR alpha may protect against drug-induced liver injury.
Keywordliver injury metabolomics PPAR alpha acylcarnitines
DOI10.1093/toxsci/kfz146
Indexed BySCI ; SCI
Language英语
WOS Research AreaToxicology
WOS SubjectToxicology
WOS IDWOS:000493388700001
Citation statistics
Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/70958
Collection植物化学与西部植物资源持续利用国家重点实验室
Corresponding AuthorTang, Ying-Mei; Li, Fei
Affiliation1.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China
2.Kunming Med Univ, Sch Pharmaceut Sci, Kunming 650500, Yunnan, Peoples R China
3.Kunming Med Univ, Yunnan Key Lab Pharmacol Nat Prod, Kunming 650500, Yunnan, Peoples R China
4.Kunming Med Univ, Affiliated Hosp 2, Yunnan Res Ctr Liver Dis, Dept Gastroenterol, Kunming 650033, Yunnan, Peoples R China
5.Yunnan Prov 1st Peoples Hosp, Dept Gen Surg, Kunming 650032, Yunnan, Peoples R China
6.Kunming Med Univ, Affiliated Hosp 2, Clin Lab, Kunming 650033, Yunnan, Peoples R China
7.NCI, Lab Metab, NIH, Ctr Canc Res, Bethesda, MD 20892 USA
Recommended Citation
GB/T 7714
Hu, Dan-Dan,Zhao, Qi,Cheng, Yan,et al. The Protective Roles of PPAR alpha Activation in Triptolide-Induced Liver Injury[J]. TOXICOLOGICAL SCIENCES,2019,171(1):1-12.
APA Hu, Dan-Dan.,Zhao, Qi.,Cheng, Yan.,Xiao, Xue-Rong.,Huang, Jian-Feng.,...&Li, Fei.(2019).The Protective Roles of PPAR alpha Activation in Triptolide-Induced Liver Injury.TOXICOLOGICAL SCIENCES,171(1),1-12.
MLA Hu, Dan-Dan,et al."The Protective Roles of PPAR alpha Activation in Triptolide-Induced Liver Injury".TOXICOLOGICAL SCIENCES 171.1(2019):1-12.
Files in This Item: Download All
File Name/Size DocType Version Access License
Hu-2019-The Protecti(1740KB)期刊论文出版稿开放获取CC BY-NC-SAView Download
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Hu, Dan-Dan]'s Articles
[Zhao, Qi]'s Articles
[Cheng, Yan]'s Articles
Baidu academic
Similar articles in Baidu academic
[Hu, Dan-Dan]'s Articles
[Zhao, Qi]'s Articles
[Cheng, Yan]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Hu, Dan-Dan]'s Articles
[Zhao, Qi]'s Articles
[Cheng, Yan]'s Articles
Terms of Use
No data!
Social Bookmark/Share
File name: Hu-2019-The Protective Roles of PPAR alpha Act.pdf
Format: Adobe PDF
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.