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Gallic acid, a natural polyphenol, protects against tert-butyl hydroperoxide- induced hepatotoxicity by activating ERK-Nrf2-Keap1-mediated antioxidative response
Feng R.-B.2; Wang Y.2; He C.2; Yang Y.1; Wan J.-B.2
2018-09-01
Source PublicationFood and Chemical Toxicology
ISSN18736351 02786915
Volume119Pages:479-488
Abstract

Gallic acid (GA), a natural polyphenol, has been shown to exert a variety of heath promoting effects. We herein investigated the critical role of nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant response in the protection of GA against tert-butyl hydroperoxide (t-BHP)-induced hepatotoxicity in L02 cells. Pretreatment of GA prevented the hepatocytotoxicity induced by t-BHP, as evidenced by the facts that GA suppressed t-BHP-induced cytotoxicity and reactive oxygen species (ROS) generation. GA induced nuclear translocation of Nrf2 along with expression of target proteins, including heme oxygenase-1 (HO-1) and glutamate cysteine ligase catalytic modify subunit (GCLC), and increased intracellular glutathione (GSH) content. Additionally, GA induced phosphorylated activation of extracellular regulated kinase (ERK), and ERK inhibitor PD98059 partially decreased GA-induced hepatoprotection, and downregulated the increased protein expressions of Nrf2, GCLC and HO-1 induced by GA. Interestingly, we found that GA could enhance the thermal stability of Keap1, which indicated the potential interaction between GA and Keap1. Furthermore, molecular docking indicated that GA possibly competed with Nrf2 for binding to Keap1. Collectively, GA effectively protects against t-BHP-induced hepatotoxicity via inducing ERK/Nrf2-mediated antioxidative signaling pathway. Meanwhile, GA disturbs protein-protein interaction between Keap1 and Nrf2 which might also contribute to nuclear translocation of Nrf2.

KeywordGallic Acid Nuclear Factor Erythroid 2-related Factor 2 Oxidative Stress Tert-butyl Hydroperoxide
DOI10.1016/j.fct.2017.10.033
URLView the original
Indexed BySCI
WOS Research AreaFood Science & Technology ; Toxicology
WOS SubjectFood Science & Technology ; Toxicology
WOS IDWOS:000443664200057
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Cited Times [WOS]:13   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Sun Yat-Sen University
2.Universidade de Macau
Recommended Citation
GB/T 7714
Feng R.-B.,Wang Y.,He C.,et al. Gallic acid, a natural polyphenol, protects against tert-butyl hydroperoxide- induced hepatotoxicity by activating ERK-Nrf2-Keap1-mediated antioxidative response[J]. Food and Chemical Toxicology,2018,119:479-488.
APA Feng R.-B.,Wang Y.,He C.,Yang Y.,&Wan J.-B..(2018).Gallic acid, a natural polyphenol, protects against tert-butyl hydroperoxide- induced hepatotoxicity by activating ERK-Nrf2-Keap1-mediated antioxidative response.Food and Chemical Toxicology,119,479-488.
MLA Feng R.-B.,et al."Gallic acid, a natural polyphenol, protects against tert-butyl hydroperoxide- induced hepatotoxicity by activating ERK-Nrf2-Keap1-mediated antioxidative response".Food and Chemical Toxicology 119(2018):479-488.
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