Squadrito F, Altavilla D, Campo G M, Calapai G, Ioculano M, Zingarelli B, Saitta A, Prosdocimi M, Caputi A P
Institute of Pharmacology, School of Medicine, University of Messina, Italy.
Eur J Pharmacol. 1992 Jan 14;210(2):107-13. doi: 10.1016/0014-2999(92)90660-v.
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.
通过静脉注射肠炎沙门氏菌脂多糖（LPS；20毫克/千克静脉注射）诱导雄性大鼠发生内毒素休克。然后评估存活率、巨噬细胞和血清肿瘤坏死因子（TNF-α）、平均动脉血压（MAP）和白细胞计数。此外，还研究了氯克罗孟对腹膜巨噬细胞吞噬作用以及致敏腹膜巨噬细胞释放TNF-α的体外作用。给予LPS导致动物死亡（内毒素攻击后24小时存活率为0%）、低血压、明显的白细胞减少，并增加血清和巨噬细胞上清液中TNF-α的水平。给予氯克罗孟（内毒素攻击后15分钟静脉注射0.5、1和2毫克/千克）可预防LPS诱导的致死性（内毒素攻击后24小时存活率为100%），逆转LPS诱导的低血压和白细胞减少，并降低血清和巨噬细胞上清液中TNF-α的水平。最后，体外将氯克罗孟添加到从内毒素处理的大鼠收集的腹膜巨噬细胞中，可增加巨噬细胞吞噬作用，并减少活化单核吞噬细胞产生TNF-α。我们的数据表明，氯克罗孟通过抑制TNF-α的产生提高内毒素休克的存活率。
