title: Quercetin protects mouse liver against nickel-induced DNA methylation and inflammation associated with the Nrf2/HO-1 and p38/STAT1/NF-κB pathway.
abstract: Quercetin (QE), a natural flavonoid, has been reported to have many benefits and medicinal properties. However, its protective effects against nickel (Ni) induced injury in liver have not been clarified. The aim of the present study was to investigate the effects of quercetin on hepatic DNA methylation and inflammation in mice exposed to nickel. ICR mice were exposed to nickel sulfate with or without quercetin co-administration for 20 days. Our results showed that quercetin administration significantly inhibited nickel-induced liver injury, which was indicated by diagnostic indicators. In exploring the underlying mechanisms of quercetin action, we found that quercetin decreased total DNA methyltransferases (DNMTs) activity and DNA methylation level of the NF-E2 related factor 2 (Nrf2) DNA in livers of nickel-treated mice. Quercetin also induced Nrf2 nuclear translocation and heme oxygenase-1 (HO-1) activity. Moreover, quercetin decreased production of pro-inflammatory markers including TNF-α, IL-1β and iNOS. Quercetin significantly inhibited the p38 and signal transducer and activator of transcription 1 (STAT1) activation, which in turn inactivated NF-κB and the inflammatory cytokines in livers of the nickel-treated mice. In conclusion, these results suggested that the inhibition of nickel-induced inflammation by quercetin is associated with its ability to modulate Nrf2/HO-1 and p38/STAT1/NF-κB signaling pathway.
authors.affiliation: School of Life Science, Jiangsu Normal University, No. 101, Shanghai Road, Tangshan New Area, 221116, Xuzhou City, Jiangsu Province, China. Electronic address: lcm9009@126.com.
authors.forename: Chan-Min
authors.initials: CM
authors.lastname: Liu
authors.affiliation: School of Chemistry and Pharmaceutical Engneering, Sichuan University of Science and Engineering, No. 180, Huixing Road, 643000, Zigong City, Sichuan Province, China.
authors.forename: Jie-Qiong
authors.initials: JQ
authors.lastname: Ma
authors.affiliation: School of Chemistry and Pharmaceutical Engneering, Sichuan University of Science and Engineering, No. 180, Huixing Road, 643000, Zigong City, Sichuan Province, China.
authors.forename: Wan-Ru
authors.initials: WR
authors.lastname: Xie
authors.affiliation: School of Life Science, Jiangsu Normal University, No. 101, Shanghai Road, Tangshan New Area, 221116, Xuzhou City, Jiangsu Province, China.
authors.forename: Si-Si
authors.initials: SS
authors.lastname: Liu
authors.affiliation: School of Life Science, Jiangsu Normal University, No. 101, Shanghai Road, Tangshan New Area, 221116, Xuzhou City, Jiangsu Province, China.
authors.forename: Zhao-Jun
authors.initials: ZJ
authors.lastname: Feng
authors.affiliation: School of Life Science, Jiangsu Normal University, No. 101, Shanghai Road, Tangshan New Area, 221116, Xuzhou City, Jiangsu Province, China.
authors.forename: Gui-Hong
authors.initials: GH
authors.lastname: Zheng
authors.affiliation: School of Life Science, Jiangsu Normal University, No. 101, Shanghai Road, Tangshan New Area, 221116, Xuzhou City, Jiangsu Province, China.
authors.forename: Ai-Min
authors.initials: AM
authors.lastname: Wang
mesh_terms: D000818:Animals; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism* / Q000517:prevention & control*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008813:Mice, Inbred ICR; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009532:Nickel / Q000633:toxicity; D020011:Protective Agents / Q000494:pharmacology*; D011794:Quercetin / Q000494:pharmacology*; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D020011:Protective Agents; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D009532:Nickel; D011794:Quercetin; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Inflammation; Liver; Nickel; Nrf2; Quercetin; STAT1