Antiplatelet activity of 3-butyl-6-bromo-1(3H)-isobenzofuranone on rat platelet aggregation

This study aimed to explore the impact of 3-butyl-6-bromo-1(3H)-isobenzofuranone (Br-NBP) on rat platelet aggregation induced by arachidonic acid (AA). Antiplatelet activities in vitro and ex vivo in rat platelets and the possible mechanism were also investigated. The 50% inhibitory concentration (IC50) of Br-NBP was 84 mu M in washed platelet added AA (final concentration, 780 mu M) in vitro, meanwhile intravenous injection of Br-NBP also potently inhibited platelet aggregation ex vivo. Br-NBP significantly restrained thromboxane B-2 formation and Ca2+ mobilization caused by AA, but failed to regulate 6-keto-prostaglandin F-1 alpha production and malonaldehyde content. Treatment of Br-NBP improved cAMP, cGMP levels and NO synthesis but prevented serotonin secretion and PF4 release. Results suggested that Br-NBP inhibited rat platelet aggregation and that the anti-platelet activity was related to both arachidonic acid cascade and cGMP-NO signal path.