Cloricromene, a coumarine derivative, protects against lethal endotoxin shock in rats.
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.
Squadrito
F
F
Institute of Pharmacology, School of Medicine, University of Messina, Italy.
Altavilla
D
D
Campo
G M
GM
Calapai
G
G
Ioculano
M
M
Zingarelli
B
B
Saitta
A
A
Prosdocimi
M
M
Caputi
A P
AP
D000818:Animals; D001681:Biological Assay; D001794:Blood Pressure / Q000187:drug effects; D002866:Chromonar / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D066298:In Vitro Techniques; D007958:Leukocyte Count / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010529:Peritoneal Cavity / Q000166:cytology; D051381:Rats; D011919:Rats, Inbred Strains; D012772:Shock, Septic / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control*; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha; C025945:cloricromen; D002866:Chromonar