title: Puerarin protects mouse liver against nickel-induced oxidative stress and inflammation associated with the TLR4/p38/CREB pathway.
abstract: Nickel (Ni), one of hazardous environmental chemicals, is known to cause liver injury. Accumulating evidence showed that puerarin (PU) possessed comprehensive biological effects. The purpose of the current study was to test the hypothesis that the puerarin protects against enhanced liver injury caused by Ni in mice. ICR mice received intraperitoneally nickel sulfate (20 mg/kg/body weight, daily) for 20 days, and puerarin (200 and 400 mg/kg/body weight) was applied before Ni exposure. The results indicated that puerarin markedly inhibited Ni-induced liver injury, which was characterized by decreased aminotransferase activities and inflammation. Puerarin also inhibited the oxidative stress and decreased the metallothionein (MT) levels. Puerarin decreased the level of pro-inflammatory cytokines TNF-α and IL-6 in livers. Puerarin significantly inhibited the TLR4 activation and p38 MAPK phosphorylation, which in turn inhibited NF-κB activity. Likewise, Ni-induced inflammatory responses were diminished by puerarin as observed by a remarkable reduction in the levels of phosphorylated CREB. Furthermore, puerarin also reduced inflammatory mediators such as cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) levels in livers. Data from this study suggested that the inhibition of Ni-induced oxidative stress and inflammatory responses by puerarin is due to its ability to modulate the TLR4/p38/CREB signaling pathway.
authors.affiliation: School of Life Science, Jiangsu Normal University, No. 101, Shanghai Road, Tangshan New Area, 221116, Xuzhou City, Jiangsu Province, PR 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, PR China.
authors.forename: Jie-Qiong
authors.initials: JQ
authors.lastname: Ma
authors.affiliation: School of Life Science, Jiangsu Normal University, No. 101, Shanghai Road, Tangshan New Area, 221116, Xuzhou City, Jiangsu Province, PR 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, PR 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, PR China.
authors.forename: Ai-Min
authors.initials: AM
authors.lastname: Wang
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D017362:Cyclic AMP Response Element-Binding Protein / Q000276:immunology; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D007529:Isoflavones / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009532:Nickel / Q000008:administration & dosage / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D007529:Isoflavones; D020011:Protective Agents; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C029938:nickel sulfate; D009532:Nickel; D048051:p38 Mitogen-Activated Protein Kinases; C033607:puerarin
keywords: CREB; Inflammation; Liver; Nickel; Puerarin; TLR4