Antioxidatives Ebselen inhibiert die thrombozytäre CD62P-Expression und wirkt anti-thrombogen in vivo

Abstract

Ebselen, a seleno-organic compound showing glutathione peroxidase-like activity, has potent anti-inflammatory and anti-oxidant effects. Since selenium deficiency is thought to be associated with an increased incidence of vascular thrombosis, we studied the effect of ebselen on blood cell aggregate formation and vessel occlusion in vivo. In individual microvessels of rat cremaster muscle preparations photochemically induced thrombus formation was analyzed in detail using intravital fluorescence microscopy. In ebselen-pretreated animals (30 mg/kg ip), venular thrombus formation was significantly delayed (50% vessel occlusion: 535 ± 34s; initial stasis: 872 ± 82s; complete occlusion: 908 ± 87s) as compared to vehicle-treated controls (416 ± 42s; 612 ± 49s; 647 ± 51s). Moreover, ebselen significantly prolonged the kinetics of arteriolar thrombus formation and even completely prevented blood cell aggregate and thrombus formation in 88.9% of all arterioles studied (p < 0.05 vs controls: 37.5%). As assessed by flow cytometry, oxidant stress-induced upregulation of CD62P on isolated platelets was found dose-dependently inhibited by increasing concentrations of ebselen (10 – 100 μM), suggesting that the antithrombotic effect of ebselen is achieved by attenuation of CD62P-dependent platelet/leukocyte aggregation. Thus, ebselen represents preventive and therapeutic value for disorders with increased risk for oxidant stress-associated thrombotic events.