CLORICROMENE, A COUMARIN DERIVATIVE, PROTECTS AGAINST LETHAL ENDOTOXIN-SHOCK IN RATS

被引:30
|
作者
SQUADRITO, F
ALTAVILLA, D
CAMPO, GM
CALAPAI, G
IOCULANO, M
ZINGARELLI, B
SAITTA, A
PROSDOCIMI, M
CAPUTI, AP
机构
[1] UNIV MESSINA,SCH MED,CHAIR MED THERAPEUT,I-98100 MESSINA,ITALY
[2] FIDIA RES LABS,ABANO TERME,ITALY
关键词
CLORICROMENE; TUMOR NECROSIS FACTOR (TNF-ALPHA); ENDOTOXIN SHOCK;
D O I
10.1016/0014-2999(92)90660-V
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 Iethality (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.
引用
收藏
页码:107 / 113
页数:7
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