Hirulog(TM) is a thrombin catalytic site inhibitor which exhibits specificity for the anionic binding exosite of alpha thrombin. Here, we have evaluated the effect of Hirulog(TM) (1, 5 and 10 mg/kg, 30 min pretreatment) in a rat model of endotoxemia. Intravenous injection of lipopolysaccharide from E. coli (25 mg/kg) serotype 0127:B8) caused decreases in blood pressure which were significantly reduced (about 60%) in animals pretreated with Hirulog(TM). Rat survival to endotoxin was significantly increased in Hirulog(TM) pretreated group (5 and 10 mg/kg) up to 24 hours. Hirulog(TM) at the dose of 10 mg/kg inhibited both endotoxin-induced leukopenia at 30 and 60 minute points and thrombocytopenia at 30 minute point but not at 90 and 120 minute points. Fibrinogen levels were significantly reduced after 2 hours following endotoxin administration. Pretreatment with Hirulog(TM) (5-10 mg/kg i.v.) 30 min prior to administration of endotoxin prevented changes in fibrinogen plasma levels. These results demonstrate that Hirulog(TM)-induced inhibition of thrombin is effective in reducing toxic and lethal effects of endotoxin.
Hirulog effect in rat endotoxin shock / Cicala, Carla; Bucci, Mariarosaria; Maraganore, J. M.; Cirino, Giuseppe. - In: LIFE SCIENCES. - ISSN 0024-3205. - STAMPA. - 57:20(1995), pp. PL 307-PL 313. [10.1016/0024-3205(95)02170-N]
Hirulog effect in rat endotoxin shock
CICALA, CARLA;BUCCI, MARIAROSARIA;CIRINO, GIUSEPPE
1995
Abstract
Hirulog(TM) is a thrombin catalytic site inhibitor which exhibits specificity for the anionic binding exosite of alpha thrombin. Here, we have evaluated the effect of Hirulog(TM) (1, 5 and 10 mg/kg, 30 min pretreatment) in a rat model of endotoxemia. Intravenous injection of lipopolysaccharide from E. coli (25 mg/kg) serotype 0127:B8) caused decreases in blood pressure which were significantly reduced (about 60%) in animals pretreated with Hirulog(TM). Rat survival to endotoxin was significantly increased in Hirulog(TM) pretreated group (5 and 10 mg/kg) up to 24 hours. Hirulog(TM) at the dose of 10 mg/kg inhibited both endotoxin-induced leukopenia at 30 and 60 minute points and thrombocytopenia at 30 minute point but not at 90 and 120 minute points. Fibrinogen levels were significantly reduced after 2 hours following endotoxin administration. Pretreatment with Hirulog(TM) (5-10 mg/kg i.v.) 30 min prior to administration of endotoxin prevented changes in fibrinogen plasma levels. These results demonstrate that Hirulog(TM)-induced inhibition of thrombin is effective in reducing toxic and lethal effects of endotoxin.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.