title: [Protective effects of agmatine on lipopolysaccharide -induced acute hepatic injury in mice].
abstract: OBJECTIVE
  To observe the effect of agmatine ( AGM) on lipopolysaccharide ( LPS )-induced acute hepatic injury in mice, and to explore its related mechanism.
  
  
  METHODS
  Sixty C57BU6 mice were randomly divided into control group ( n = 20, with intra-peritoneal injection of phosphate buffer saline 10 mg/kg), model group ( n = 20, with intra-peritoneal injection of LPS 10 mg/kg), and AGM group (n=20, with intra-peritoneal injection of LPS 10 mg/kg and AGM 200 mg/kg). Ten mice in each group were sacrificed at 6 hours and 24 hours, respectively, after modeling, blood samples were collected for the determination of tumor necrosis factor-a ( TNF -a) and interleukin ( IL-113 and IL-6) by enzyme linked immunosorbent assay (ELISA) at 6 hours after modeling , and for determination of alanine aminotransferase (ALT), aspartate transaminase (AST) and total bilirubin (TBil) by automatic biochemistry analyzer at 24 hours after modeling. Hepatic homogenate was also collected for determining the endo nuclear nuclear factor-KB ( NF -KB) p65 by Western blotting at 6 hours after modeling, and for observation of pathological changes at 24 hours after modeling.
  
  
  RESULTS
  At 6 hours after modeling, .the mice in model group became lethargic and quiet, and their food and water assumption was reduced, but AGM was found to be able to greatly improve the general status of animals in AGM group. AGM was found to lower the contents of serum TNF-a ( IJ.g/L: 296.3 ± 42.5 vs. 627.2 ± 81.3, t=7.327, P=0.002), IL-113 ( f.Lg/L: 109.1 ± 12.3 vs. 264.2 ± 18.8, t= 11.958, P=0.001), IL-6 ( mg/L: 11.4 ± 1.9 vs. 23.6 ± 2.5, t=6.729, P=0.003), ALT (U!L: 107.9 ± 8.5 vs. 189.9 ± 13.6, t=8.856, P=0.001 ), AST (UIL: 347.4 ± 24.9 vs. 716.8 ± 60.4, t=9.793, P=0.001) and TBil ( f.Lmol!L: 8.3 ± 0.9 vs. 10.6 ± 0.5, t=3.869, P=0.018) in mice with acute hepatic injury induced by LPS. AGM also depressed TNF -a ( ng/g: 287.4 ± 32.5 vs. 461.5 ± 31.4, t=6.673, P= 0.003), IL-113 (pg/g: 146.7 ± 13.5 vs. 351.6 ± 28.7, t=11.190, P=0.001) and intranuclear NF-KB p65 level (NF-KBp65/TBP: 0.515 ± 0.060 vs. 0.853 ± 0.080, t=5.849, P=0.004) in liver tissue. Histological examination demonstrated that AGM significantly reduced liver injury caused by LPS, as manifested in amelioration of hepatocytes swelling, necrosis and neutrophil infiltration.
  
  
  CONCLUSIONS
  Agmatine can reduce LPS-induced acute hepatic injury in mice via suppressing NF-κB translocation and reduction of the synthesis and release of cytokines.
authors.forename: Xuan -fei
authors.initials: X-
authors.lastname: Li
authors.forename: Xia
authors.initials: X
authors.lastname: Fan
authors.forename: Zhi-hua
authors.initials: ZH
authors.lastname: Zheng
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Jian-ping
authors.initials: JP
authors.lastname: Gong
authors.forename: Hua-ping
authors.initials: HP
authors.lastname: Liang
mesh_terms: D000376:Agmatine / Q000494:pharmacology*; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000097:blood; D008070:Lipopolysaccharides / Q000009:adverse effects; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; C498145:Rela protein, rat; D051996:Transcription Factor RelA; D000376:Agmatine