title: Anti-endotoxic shock effects of cyproheptadine in rats.
abstract: OBJECTIVE
  To investigate the antagonistic effect and mechanism of the effect of cyproheptadine (Cyp) on endotoxic shock in rats.
  
  
  METHODS
  Endotoxic shock was produced in rats by i.v. injection of lipopolysaccharides (LPS) (5 mg/kg). Tumor necrosis factor (TNF(alpha)) mRNA expression was assessed by Northern blot. Plasma TNF(alpha) content was measured by radioimmunoassay. Plasma superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were measured. The intracellular free calcium concentration ([Ca(2+)](i)) in single endothelial cells was determined by laser scanning confocal microscopy (LSCM).
  
  
  RESULTS
  Cyp 5 mg/kg injected immediately after i.v. LPS raised the mean arterial blood pressure (MABP) of shocked rats and improved their 24 h survival rate. Meanwhile, Cyp markedly decreased TNF(alpha) mRNA levels in rat liver (18 +/- 10 vs. LPS + saline 38 +/- 10, P < 0.01) as well as plasma TNF(alpha) content [(7.8 +/- 2.4) microg/L vs. LPS + saline (21.5 +/- 3.2) microg/L, P < 0.01)]. It enhanced plasma SOD activity [(1037.2 +/- 112.8) NU/L vs LPS + saline (615.4 +/- 92.6) NU/L, P < 0.01], reduced the MDA content [(5.2 +/- 1.1) micromol/L vs. LPS + saline (9.8 +/- 1.5) micromol/L, P < 0.01], and inhibited TNF(alpha)-induced [Ca(2+)](i) elevation.
  
  
  CONCLUSIONS
  Cyp exerts an anti-endotoxic shock effect by inhibiting TNF(alpha) gene expression, enhancing SOD activity, reducing lipid peroxidation, and preventing [Ca(2+)](i) overload.
authors.affiliation: Department of Pathophysiology, Jining Medical College, Jining 272013, China. wangLZ1@ji-public.sd.cninfo.net
authors.forename: Lizan
authors.initials: L
authors.lastname: Wang
authors.forename: Qingzhu
authors.initials: Q
authors.lastname: Zhang
authors.forename: Xiuzhou
authors.initials: X
authors.lastname: Hu
authors.forename: Ning
authors.initials: N
authors.lastname: Lun
authors.forename: Baosheng
authors.initials: B
authors.lastname: Wang
authors.forename: Fanhe
authors.initials: F
authors.lastname: Zhu
mesh_terms: D000818:Animals; D003533:Cyproheptadine / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D008315:Malondialdehyde / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000188:drug therapy* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
chemical_list: D006634:Histamine H1 Antagonists; D014409:Tumor Necrosis Factor-alpha; D003533:Cyproheptadine; D008315:Malondialdehyde; D013482:Superoxide Dismutase