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

Ling-ling Zhou; Cong Zhou; Xiao-wen Liang; Zhe Feng; Zhang-pu Liu; Hao-lu Wang; Xue-ping Zhou

doi:10.1007/s11655-017-2546-6

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

Updated：2021-08-27

- Self-protection against triptolide-induced toxicity in human hepatic cells via Nrf2-ARE-NQO1 pathway
- Chinese Journal of Integrative Medicine Vol. 23, Issue 12, Pages: 929-936(2017)
- Affiliations：
  
  1. School of Pharmacy, The First Clinical Medical College, Nanjing University of Chinese Medicine,Nanjing,China
  2. Department of Pharmacy, Wuxi No.9 People’s Hospital, Soochow University, Wuxi Hand Surgery Hospital,Jiangsu Province,Wuxi,China
  3. Therapeutics Research Centre, School of Medicine, The University of Queensland, Princess Alexandra Hospital, Woolloongabba,Australia
- Author bio：
- Funds：
  
  Supported by National Natural Science Foundation of China (No. 81072749, 81573869), National Natural Science Foundation for the Youth of Jiangsu Province (No. BK20140960) and National Natural Science Pre-research of Nanjing University of Chinese Medicine (No. 14XYY01, 14XYY10)
- DOI：10.1007/s11655-017-2546-6
  CLC：
- Published：2017，
  
  Published Online：18 May 2017，
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Zhou, Ll., Zhou, C., Liang, Xw. et al. Self-protection against triptolide-induced toxicity in human hepatic cells via Nrf2-ARE-NQO1 pathway., Chin. J. Integr. Med. 23, 929–936 (2017). https://doi.org/10.1007/s11655-017-2546-6

Ling-ling Zhou, Cong Zhou, Xiao-wen Liang, et al. Self-protection against triptolide-induced toxicity in human hepatic cells via Nrf2-ARE-NQO1 pathway. [J]. Chinese Journal of Integrative Medicine 23(12):929-936(2017)
Zhou, Ll., Zhou, C., Liang, Xw. et al. Self-protection against triptolide-induced toxicity in human hepatic cells via Nrf2-ARE-NQO1 pathway., Chin. J. Integr. Med. 23, 929–936 (2017). https://doi.org/10.1007/s11655-017-2546-6 DOI：

Ling-ling Zhou, Cong Zhou, Xiao-wen Liang, et al. Self-protection against triptolide-induced toxicity in human hepatic cells via Nrf2-ARE-NQO1 pathway. [J]. Chinese Journal of Integrative Medicine 23(12):929-936(2017) DOI： 10.1007/s11655-017-2546-6.

摘要

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. 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 identified. Meanwhile

shRNA was used to silence Nrf2 in L-02 cells to find out whether Nrf2 plays a protective role. 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 or 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 or 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 or P<0.01). 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.

Abstract

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 identified. Meanwhile

shRNA was used to silence Nrf2 in L-02 cells to find out whether Nrf2 plays a protective role. 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 or 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 or 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 or P<0.01). 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.

关键词

triptolide human hepatic cellsNF-E2-related factor 2oxidative stressliver injury

Keywords

triptolide human hepatic cellsNF-E2-related factor 2oxidative stressliver injury

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