Sonia Varghese

Grape seed and skin extracts inhibit platelet function and release of reactive oxygen intermediates.

Red wine and purple grape juice contain polymeric flavonoids with antioxidant properties believed to be protective against cardiovascular events but the alcohol and sugar content of these beverages has curtailed their medicinal use. Acute cardiac events are also associated with enhanced inflammation and thrombosis. In this study, the extracts from grape skins or seeds were examined for their anti-inflammatory properties and effect on platelet release of reactive oxygen intermediates. Incubation of platelets with seed or skin extract led to a decrease in platelet aggregation from 68.8 ± 19.8% to 45 ± 3.6% for seeds and to 27 ± 7.2% for skin, respectively (P < 0.05). Platelet incubation with grape skin or seed extracts led to a marked decrease in superoxide release from 73 ± 6.2 to 2 ± 3.4 for grape seeds and to 0.33 ± 0.57 for grape skin (chemilum. units; P < 0.05) as well as a significant increase in radical-scavenging activity, decrease in reactive oxygen species release by confocal microscopy, and enhanced platelet NO was measured using an NO-sensitive microelectrode. These effects were dose dependent for both grape extracts. Coincubation with seeds and skins led to additive inhibition of platelet aggregation, enhanced NO release, and prevented superoxide production. Incubation with seed or skin extracts led to an immediate attenuation of release of the inflammatory mediator, soluble CD40 ligand. Thus, the extracts from purple grape skins and seeds inhibit platelet function and platelet-dependent inflammatory responses at pharmacologically relevant concentrations. These findings suggest potentially beneficial platelet-dependent antithrombotic and anti-inflammatory properties of purple grape-derived flavonoids.

CD40 Ligand Influences Platelet Release of Reactive Oxygen Intermediates

Objective—Soluble CD40 ligand (sCD40L) has been recently implicated in the pathogenesis of atherosclerosis. Elevated levels of sCD40L in acute coronary syndrome patients suggests enhanced platelet function; however, the exact mechanism by which this occurs is unknown. In this study, we examined the effect of sCD40L on platelet function and reactive oxygen and nitrogen species (RONS) generation. Methods and Results—Platelet stimulation in the presence of recombinant sCD40L (rsCD40L) led to enhanced generation of RONS as measured by DCFHDA oxidation and confocal microscopy. Incubation with rsCD40L led to enhanced platelet P-selectin expression, aggregation, and platelet-leukocyte conjugation. Platelets isolated from CD40L-deficient mice had decreased agonist-induced NO release as compared with wild-type mice. Incubation of platelets with rsCD40L enhanced stimulation-induced p38 MAP kinase and Akt phosphorylation. Conclusion—Soluble CD40L enhances platelet activation, aggregation, and platelet-leukocyte conjugation, as well as increases stimulation-induced platelet release of RONS through activation of Akt and p38 MAP kinase signaling pathways. These data suggest that sCD40L regulates platelet-dependent inflammatory and thrombotic responses that contribute to the pathogenesis of atherothrombosis.

Beyond hemostasis: The antiflammatory and antioxidant effects of dipyridamole

Platelet stimulation leads to release of reactive oxygen species (ROS) that are known to influence platelet function and thrombosis. Dipyridamole is a vasodilator and platelet inhibitor that decreases adenosine uptake and may be a highly efficient chain breaking antioxidant. The antioxidant effects of dipyridamole on platelet‐derived ROS and the potential (anti)inflammatory effects are not known.

The differential effects of orbofiban and abciximab on platelet release of nitric oxide and superoxide

Clinical Pharmacology & Therapeutics (2003) 73, P63–P63; doi: