Anti-endotoxic shock effects of cyproheptadine in rats.
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.
Wang
Lizan
L
Department of Pathophysiology, Jining Medical College, Jining 272013, China. wangLZ1@ji-public.sd.cninfo.net
Zhang
Qingzhu
Q
Hu
Xiuzhou
X
Lun
Ning
N
Wang
Baosheng
B
Zhu
Fanhe
F
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
D006634:Histamine H1 Antagonists; D014409:Tumor Necrosis Factor-alpha; D003533:Cyproheptadine; D008315:Malondialdehyde; D013482:Superoxide Dismutase