title: Activation of Nrf2 protects against triptolide-induced hepatotoxicity.
abstract: Triptolide, the major active component of Tripterygium wilfordii Hook f. (TWHF), has a wide range of pharmacological activities. However, the toxicities of triptolide, particularly the hepatotoxicity, limit its clinical application. The hepatotoxicity of triptolide has not been well characterized yet. The aim of this study was to investigate the role of NF-E2-related factor 2 (Nrf2) in triptolide-induced toxicity and whether activation of Nrf2 could protect against triptolide-induced hepatotoxicity. The results showed that triptolide caused oxidative stress and cell damage in HepG2 cells, and these toxic effects could be aggravated by Nrf2 knockdown or be counteracted by overexpression of Nrf2. Treatment with a typical Nrf2 agonist, sulforaphane (SFN), attenuated triptolide-induced liver dysfunction, structural damage, glutathione depletion and decrease in antioxidant enzymes in BALB/C mice. Moreover, the hepatoprotective effect of SFN on triptolide-induced liver injury was associated with the activation of Nrf2 and its downstream targets. Collectively, these results indicate that Nrf2 activation protects against triptolide-induced hepatotoxicity.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China; Pharmaceutical Department, Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Feihai
authors.initials: F
authors.lastname: Shen
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Cuiwen
authors.initials: C
authors.lastname: Guan
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xiaozhe
authors.initials: X
authors.lastname: Sun
authors.affiliation: Center of Laboratory Animals, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xinlu
authors.initials: X
authors.lastname: Fu
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Jin
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China; Center of Laboratory Animals, Sun Yat-sen University, Guangzhou, China.
authors.forename: Zhiying
authors.initials: Z
authors.lastname: Huang
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects* / Q000494:pharmacology; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D004224:Diterpenes / Q000009:adverse effects* / Q000494:pharmacology; D004852:Epoxy Compounds / Q000009:adverse effects / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D051267:NF-E2-Related Factor 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010616:Phenanthrenes / Q000009:adverse effects* / Q000494:pharmacology; D013454:Sulfoxides
chemical_list: D016588:Anticarcinogenic Agents; D018906:Antineoplastic Agents, Alkylating; D004224:Diterpenes; D004852:Epoxy Compounds; D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C495636:Nfe2l2 protein, mouse; D010616:Phenanthrenes; D013454:Sulfoxides; C001899:triptolide; C016766:sulforaphane