Thiosulfinates inhibit platelet aggregation and microparticle shedding at a calpain-dependent step

Thiosulfinates (TSs) are sulfur compounds generated through the processing of different Allium species with antiplatelet property. To further define t his platelet inhibitory effect we studied diallyl-TS (Al,TS), dipropyl-TS ( Pr2TS), and dimethyl-TS (Me2TS) on platelet responses. The three TSs inhibi ted dose-dependent platelet aggregation, with IC50 values of 15 +/- 2, 19 /- 2, and 9 +/- 1 muM for Al2TS, Pr2TS and Me2TS, respectively. TSs had no effect on the expression of a platelet procoagulant surface, measured by fl ow cytometry as the binding of annexin V-FITC. They inhibited the micropart icle shedding and clot retraction. Since the microparticle shedding is a ca lpain-activation dependent step, we assessed calpain activation by analysis of autoproteolysis in shorter active forms and by talin proteolysis in the presence of TSs. Calpain activation was inhibited by TSs independently of fibrinogen binding. Thus, TSs represent a new category of platelet inhibito rs, acting on calpain-induced events.