| 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
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| Corresponding Author | Tang, Ying-Mei(tangyingmei_med@163.com) ; Li, Fei(lifeib@mail.kib.ac.cn) |
| 2019-09-01 | |
| Source Publication | TOXICOLOGICAL SCIENCES
 |
| ISSN | 1096-6080 |
| Volume | 171Issue:1Pages:1-12 |
| Abstract | Triptolide (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. |
| Keyword | liver injury metabolomics PPAR alpha acylcarnitines |
| DOI | 10.1093/toxsci/kfz146 |
| Indexed By | SCI ; SCI |
| Language | 英语 |
| WOS ID | WOS:000493388700001 |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://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 Author | Tang, Ying-Mei; Li, Fei |
| Affiliation | 1.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. |
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