Self-protection against triptolide-induced toxicity in human hepatic cells via Nrf2-ARE-NQO1 pathway

Zhou, Ling-ling, Zhou, Cong, Liang, Xiao-wen, Feng, Zhe, Liu, Zhang-pu, Wang, Hao-lu and Zhou, Xue-ping (2017) Self-protection against triptolide-induced toxicity in human hepatic cells via Nrf2-ARE-NQO1 pathway. Chinese Journal of Integrative Medicine, 23 12: 929-936. doi:10.1007/s11655-017-2546-6

Author Zhou, Ling-ling
Zhou, Cong
Liang, Xiao-wen
Feng, Zhe
Liu, Zhang-pu
Wang, Hao-lu
Zhou, Xue-ping
Title Self-protection against triptolide-induced toxicity in human hepatic cells via Nrf2-ARE-NQO1 pathway
Journal name Chinese Journal of Integrative Medicine   Check publisher's open access policy
ISSN 1993-0402
Publication date 2017-05-18
Year available 2017
Sub-type Article (original research)
DOI 10.1007/s11655-017-2546-6
Open Access Status Not yet assessed
Volume 23
Issue 12
Start page 929
End page 936
Total pages 8
Place of publication Beijing, China
Publisher Chinese Journal of Integrated Traditional and Western Medicine Press
Language eng
Subject 2707 Complementary and alternative medicine
2736 Pharmacology (medical)
Abstract Objective: To find the signaling pathway of triptolide (TP)-induced liver injury and to reveal whether NF-E2-related factor 2 (Nrf2) plays an important role in cellular self-protection. Methods: The L-02 and HepG2 cells were cultured and treated with various concentrations of TP. The cell viability was observed, and the cell medium was collected for detecting the aspartate aminotransferase (ALT), alanine aminotransferase (AST), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and L-glutathione production (GSH) levels. Nrf2 and its downstream target NAD(P)H: quinine oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1) expression, the nuclear translocation of Nrf2, and the binding ability of Nrf2 and antioxidant response element (ARE) were also identifified. Meanwhile, shRNA was used to silence Nrf2 in L-02 cells to fifind out whether Nrf2 plays a protective role. Results: The viability of the L-02 and HepG2 cells treated with TP decreased in a doseand time-dependent manner, and TP (20–80 μg/mL) markedly induced the release of ALT, AST and LDH (P<0.05, P<0.01), reduced the levels of SOD and GSH (P<0.01), and increased the intracellular reactive oxygen species. Meanwhile, TP augmented the Nrf2 expression in L-02 and HepG2 cells (P<0.05, P<0.01), induced Nrf2 nuclear translocation, increased the Nrf2 ARE binding activity, and increased HO-1 and NQO1 expressions. Nrf2 knockdown revealed a more severe toxic effect of TP (P<0.05, P<0.01). Conclusions: Human hepatic cells treated with TP induced oxidative stress, and led to cytotoxicity. Self-protection against TP-induced toxicity in human hepatic cells might be via Nrf2-ARE-NQO1 transcriptional pathway.
Keyword human hepatic cells
liver injury
NF-E2-related factor 2
oxidative stress
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 81072749
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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Created: Fri, 01 Dec 2017, 00:11:38 EST