title: Tetrandrine increased the survival rate of mice with lipopolysaccharide-induced endotoxemia.
abstract: BACKGROUND
  Endotoxemia usually causes significant morbidity and mortality, and treatment of endotoxemia is often ineffective. The effects of tetrandrine (a bisbenzylisoquinoline alkaloid) on lipopolysaccharide (LPS)-induced endotoxemia were investigated in mice.
  
  
  METHODS
  The peritoneal macrophages were stimulated with LPS and treated with or without tetrandrine. The amounts of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and IL-10 secreted by peritoneal macrophages were measured by enzyme-linked immunosorbent assay. Mice were intraperitoneally injected with LPS to induce endotoxemia and were treated or not treated with oral gavage with 150 mg/kg tetrandrine 1 hour before or after LPS injection. The survival rate of the mice was determined after they were treated with various regiments. The amounts of TNF-alpha, IL-1beta, IL-6, and IL-10 in the serum of the mice were measured by enzyme-linked immunosorbent assay, and the high mobility group box 1 (HMGB1) concentration was studied by Western blot analysis.
  
  
  RESULTS
  Tetrandrine suppressed the LPS-induced increase of TNF-alpha, IL-1beta, and HMGB1 secretion by peritoneal macrophages but did not affect the IL-6 and IL-10 concentrations. The animals treated with tetrandrine either 1 hour before or after LPS injection had a 100% survival rate, which was significantly higher than that of the control group (40%) (p = 0.005). The LPS-induced increase in serum TNF-alpha, IL-1beta, and HMGB1 concentrations was reduced by tetrandrine treatment administered either 1 hour before or after LPS injection (p < 0.0001). In contrast, tetrandrine prolonged the LPS-induced elevation in serum IL-10 concentrations only mildly changed the serum IL-6 concentrations.
  
  
  CONCLUSIONS
  Tetrandrine treatment either 1 hour before or 1 hour after LPS injection reduced the mortality rate of the mice with LPS-induced endotoxemia. The effects of tetrandrine on LPS-induced endotoxemia might be related to the suppression of TNF-alpha, IL-1beta, and HMGB1 concentrations.
authors.affiliation: Department of Anesthesiology, Far-Eastern Memorial Hospital, Taipei, Taiwan.
authors.forename: Tzu-Yu
authors.initials: TY
authors.lastname: Lin
authors.forename: Sheng-Hong
authors.initials: SH
authors.lastname: Tseng
authors.forename: Shao-Jung
authors.initials: SJ
authors.lastname: Li
authors.forename: Jin-Cherng
authors.initials: JC
authors.lastname: Chen
authors.forename: Jiann-Shing
authors.initials: JS
authors.lastname: Shieh
authors.forename: Yun
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D044182:Benzylisoquinolines / Q000494:pharmacology*; D015153:Blotting, Western; D019446:Endotoxemia / Q000188:drug therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D016753:Interleukin-10 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D008070:Lipopolysaccharides; D017737:Macrophages, Peritoneal / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D044182:Benzylisoquinolines; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C009438:tetrandrine