Cloricromene, a coumarine derivative, protects against lethal endotoxin shock in rats.

Abstract

Endotoxin shock was induced in male rats by an intravenous (i.v.) injection of Salmonella enteriditis lipopolysaccharide (LPS; 20 mg/kg i.v.). Survival rate, macrophage and serum tumor necrosis factor (TNF-alpha), mean arterial blood pressure (MAP) and white blood cell count were then evaluated. Furthermore the in vitro effect of cloricromene on peritoneal macrophage phagocytosis and TNF-alpha release by primed peritoneal macrophages was investigated. LPS administration caused animal death (0% survival 24 h after endotoxin challenge), hypotension, marked leukopenia and increased the levels of TNF-alpha in both serum and macrophage supernatants. Cloricromene administration (0.5, 1 and 2 mg/kg i.v. 15 min after endotoxin) protected against LPS-induced lethality (100% survival rate 24 h after endotoxin challenge), reverted LPS-induced hypotension and leukopenia, and decreased TNF-alpha in both serum and macrophage supernatants. Finally, cloricromene, added in vitro to peritoneal macrophages collected from endotoxin-treated rats increased macrophage phagocytosis and reduced TNF-alpha formation by activated mononuclear phagocytes. Our data suggest that cloricromene increases survival rate in endotoxin shock through an inhibition of TNF-alpha production.

• Authors: F Squadrito, D Altavilla, G M Campo, G Calapai, M Ioculano, B Zingarelli, A Saitta, M Prosdocimi, A P Caputi
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 210 Issue 2 Pg. 107-13 (Jan 14 1992) ISSN: 0014-2999 [Print] Netherlands
• PMID: 1601052 (Publication Type: Journal Article)

Chemical References

• Tumor Necrosis Factor-alpha
• cloricromen
• Chromonar

Topics

• Animals
• Biological Assay
• Blood Pressure (drug effects)
• Chromonar (analogs & derivatives, pharmacology, therapeutic use)
• In Vitro Techniques
• Leukocyte Count (drug effects)
• Macrophages (drug effects, metabolism)
• Male
• Peritoneal Cavity (cytology)
• Rats
• Rats, Inbred Strains
• Shock, Septic (blood, physiopathology, prevention & control)
• Survival Rate
• Tumor Necrosis Factor-alpha (metabolism)