Puerarin protects mouse liver against nickel-induced oxidative stress and inflammation associated with the TLR4/p38/CREB pathway. (5th January 2016)

• Record Type: Journal Article
• Authors: Liu, Chan-Min; Ma, Jie-Qiong; Liu, Si-Si; Feng, Zhao-Jun; Wang, Ai-Min
• Is Part Of: Chemico-biological interactions. Volume 243(2016)
• Page Start: 29
• Page End: 34
• Publication Date: 2016-01-05
• Subjects: Puerarin -- Nickel -- Liver -- Inflammation -- TLR4 -- CREB; ALT alanine aminotransferase -- AST aspartate aminotransferase -- CREB cAMP-responsive element binding protein -- COX-2 cyclooxygenase-2 -- IL-6 interleukin-6 -- NF-κB nuclear factor-κB -- Ni nickel -- ROS reactive oxygen species -- PGE2 prostaglandin E2 -- TBARS thiobarbituric acid reactive substances -- TLR4 the Toll-like receptor 4 -- TNF-α tumor necrosis factor-alpha; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2015.11.017
• Languages: English
• ISSNs: 0009-2797

Abstract

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. Highlights: Puerarin prevented nickel-induced hepatotoxicity. Puerarin inhibited oxidative stress and inflammation in mouse livers. Puerarin decreased the phosphorylation levels of TLR4, p38, CREB in the livers. Puerarin inhibited the NF-κB activation in the livers of nickel-treated mice.