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: Jia Li, Feihai Shen, Cuiwen Guan, Wenwen Wang, Xiaozhe Sun, Xinlu Fu, Min Huang, Jing Jin, Zhiying Huang
• Journal: PloS one (PLoS One) Vol. 9 Issue 7 Pg. e100685 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24988078 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticarcinogenic Agents
• Antineoplastic Agents, Alkylating
• Diterpenes
• Epoxy Compounds
• Isothiocyanates
• NF-E2-Related Factor 2
• NFE2L2 protein, human
• Nfe2l2 protein, mouse
• Phenanthrenes
• Sulfoxides
• triptolide
• sulforaphane

Topics

• Animals
• Anticarcinogenic Agents (pharmacology)
• Antineoplastic Agents, Alkylating (adverse effects, pharmacology)
• Chemical and Drug Induced Liver Injury (metabolism, pathology, prevention & control)
• Diterpenes (adverse effects, pharmacology)
• Epoxy Compounds (adverse effects, pharmacology)
• Hep G2 Cells
• Humans
• Isothiocyanates (pharmacology)
• Mice
• Mice, Inbred BALB C
• NF-E2-Related Factor 2 (antagonists & inhibitors, metabolism)
• Oxidative Stress (drug effects)
• Phenanthrenes (adverse effects, pharmacology)
• Sulfoxides