[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. CONCLUSION: Agmatine can reduce LPS-induced acute hepatic injury in mice via suppressing NF-κB translocation and reduction of the synthesis and release of cytokines.