title: Ferulic acid protects against carbon tetrachloride-induced liver injury in mice.
abstract: Ferulic acid (FA), isolated from the root of Scrophularia buergeriana, is a phenolic compound possessing antioxidant, anticancer, and antiinflammatory activities. Here, we have investigated the hepatoprotective effect of FA against carbon tetrachloride (CCl(4))-induced acute liver injury. Mice were treated intraperitoneally with vehicle or FA (20, 40, and 80mg/kg) 1h before and 2h after CCl(4) (20μl/kg) injection. The serum activities of aminotransferases and the hepatic level of malondialdehyde were significantly higher after CCl(4) treatment, while the concentration of reduced glutathione was lower. These changes were attenuated by FA. The serum level and mRNA expression of tumor necrosis factor-α significantly increased after CCl(4) treatment, and FA attenuated these increases. The levels of inducible nitric oxide synthase and cyclooxygenase-2 protein and mRNA expression after CCl(4) treatment were significantly higher and FA reduced these increases. CCl(4)-treated mice showed increased nuclear translocation of nuclear factor-κB (NF-κB), and decreased levels of inhibitors of NF-κB in cytosol. Also, CCl(4) significantly increased the level of phosphorylated JNK and p38 mitogen-activated protein (MAP) kinase, and nuclear translocation of activated c-Jun. FA significantly attenuated these changes. We also found that acute CCl(4) challenge induced TLR4, TLR2, and TLR9 protein and mRNA expression, and FA significantly inhibited TLR4 expression. These results suggest that FA protects from CCl(4)-induced acute liver injury through reduction of oxidative damage and inflammatory signaling pathways.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Hyo-Yeon
authors.initials: HY
authors.lastname: Kim
authors.forename: Juhyun
authors.initials: J
authors.lastname: Park
authors.forename: Kwan-Hoo
authors.initials: KH
authors.lastname: Lee
authors.forename: Dong-Ung
authors.initials: DU
authors.lastname: Lee
authors.forename: Jong-Hwan
authors.initials: JH
authors.lastname: Kwak
authors.forename: Yeong Shik
authors.initials: YS
authors.lastname: Kim
authors.forename: Sun-Mee
authors.initials: SM
authors.lastname: Lee
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000302:isolation & purification / Q000627:therapeutic use*; D015153:Blotting, Western; D002251:Carbon Tetrachloride / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D003373:Coumaric Acids / Q000008:administration & dosage / Q000302:isolation & purification / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood; D007274:Injections, Intraperitoneal; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018384:Oxidative Stress / Q000187:drug effects; D018517:Plant Roots / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D032266:Scrophularia / Q000737:chemistry; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003373:Coumaric Acids; D016207:Cytokines; D051193:Toll-Like Receptors; C004999:ferulic acid; D002251:Carbon Tetrachloride