title: A novel fibrinogenase from Agkistrodon acutus venom protects against LPS-induced endotoxemia via regulating NF-κB pathway.
abstract: BACKGROUND
  Endotoxins including lipopolysaccharide (LPS) could cause endotoxemia which often results in excessive inflammation, organ dysfunction, sepsis, disseminated intravascular coagulation (DIC) or even death. Previously, a novel fibrinogenase (FII) showed protective effects on LPS-induced DIC via activating protein C and suppressing inflammatory cytokines.
  
  
  OBJECTIVE
  To evaluate whether FII has protective effect on LPS-induced endotoxemia in mice and learn about the role of NF-κB pathway in TNF-α producing process.
  
  
  METHODS
  BALB/C mice were intraperitoneally injected (i.p.) with (a) 30 mg/kg LPS, (b) LPS + 0.3 mg/kg FII, (c) LPS + 1.0 mg/kg FII, (d) LPS + 3.0 mg/kg FII or (e) saline. Both survival rate and organ function were tested, including alanine aminotransferase (ALT), blood urine nitrogen (BUN) and tissue section, and TNF-α was examined by ELISA. RAW 264.7 macrophage was administered with (a) LPS, (b) LPS + FII, (c) FII alone or (d) saline, and TNF-α and phosphorylation (P)-NF-κB (P65) were determined by Western blot.
  
  
  RESULTS
  The administration of LPS led to 65% mortality rate, a rise of serum TNF-α, BUN and ALT levels, and both liver and renal tissue damage were observed. While FII treatment significantly increased the survival rate of LPS-induced endotoxemia mice model, histopathology and protein analysis results also revealed that FII remarkably protected liver and renal from LPS damage as well as decreasing TNF-α level. In vitro, FII significantly decreased LPS-induced TNF-α production and the expression of P-NF-κB (P65).
  
  
  CONCLUSIONS
  Our findings suggested that FII had protective effect on LPS-induced endotoxemia and organ injuries by suppressing the activation of NF-κB which decreased TNF-α level.
authors.affiliation: a Key Laboratory for Regenerative Medicine, Ministry of Education .|b Department of Developmental and Regenerative Biology , and.
authors.forename: Yingwei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: a Key Laboratory for Regenerative Medicine, Ministry of Education .|b Department of Developmental and Regenerative Biology , and.
authors.forename: Zixi
authors.initials: Z
authors.lastname: Qin
authors.affiliation: c Department of Pharmacology , Medical College , and.
authors.forename: Shuhao
authors.initials: S
authors.lastname: Shen
authors.affiliation: c Department of Pharmacology , Medical College , and.
authors.forename: Nanlin
authors.initials: N
authors.lastname: Xiang
authors.affiliation: c Department of Pharmacology , Medical College , and.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: c Department of Pharmacology , Medical College , and.
authors.forename: Xi
authors.initials: X
authors.lastname: Lin
authors.affiliation: d Department of Physiology , Medical College, Jinan University , Guangzhou , China.
authors.forename: Zhiquan
authors.initials: Z
authors.lastname: Bai
authors.affiliation: a Key Laboratory for Regenerative Medicine, Ministry of Education .|b Department of Developmental and Regenerative Biology , and.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wu
mesh_terms: D000818:Animals; D003435:Crotalid Venoms / Q000737:chemistry*; D019446:Endotoxemia / Q000139:chemically induced* / Q000276:immunology / Q000517:prevention & control*; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D012697:Serine Endopeptidases / Q000494:pharmacology*; D017819:Viperidae
chemical_list: D003435:Crotalid Venoms; D008070:Lipopolysaccharides; D012697:Serine Endopeptidases; C412879:venombin B
keywords: Anti-endotoxemia; FII; NF-κB phosphorylation; anti-inflammatory activity; lipopolysaccharide