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Anti-endotoxic shock effects of cyproheptadine in rats / 中华医学杂志(英文版)
Chinese Medical Journal ; (24): 443-445, 2002.
Article in English | WPRIM | ID: wpr-302305
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the antagonistic effect and mechanism of the effect of cyproheptadine (Cyp) on endotoxic shock in rats.</p><p><b>METHODS</b>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).</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>
Subject(s)
Full text: Available Index: WPRIM (Western Pacific) Main subject: Pharmacology / Shock, Septic / Superoxide Dismutase / Blood / Tumor Necrosis Factor-alpha / Rats, Wistar / Cyproheptadine / Drug Therapy / Genetics / Histamine H1 Antagonists Limits: Animals Language: English Journal: Chinese Medical Journal Year: 2002 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Pharmacology / Shock, Septic / Superoxide Dismutase / Blood / Tumor Necrosis Factor-alpha / Rats, Wistar / Cyproheptadine / Drug Therapy / Genetics / Histamine H1 Antagonists Limits: Animals Language: English Journal: Chinese Medical Journal Year: 2002 Type: Article