Anti-endotoxic shock effects of cyproheptadine in rats.
- Author:
Lizan WANG
1
;
Qingzhu ZHANG
;
Xiuzhou HU
;
Ning LUN
;
Baosheng WANG
;
Fanhe ZHU
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Cyproheptadine; pharmacology; Histamine H1 Antagonists; pharmacology; Malondialdehyde; blood; Rats; Rats, Wistar; Shock, Septic; drug therapy; metabolism; Superoxide Dismutase; blood; Tumor Necrosis Factor-alpha; biosynthesis; genetics
- From: Chinese Medical Journal 2002;115(3):443-445
- CountryChina
- Language:English
-
Abstract:
OBJECTIVETo investigate the antagonistic effect and mechanism of the effect of cyproheptadine (Cyp) on endotoxic shock in rats.
METHODSEndotoxic 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).
RESULTSCyp 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.
CONCLUSIONCyp exerts an anti-endotoxic shock effect by inhibiting TNF(alpha) gene expression, enhancing SOD activity, reducing lipid peroxidation, and preventing [Ca(2+)](i) overload.
