ABSTRACT
The effects of hexahydrocurcumin on adenosine diphosphate (ADP)-induced human platelet aggregation were studied. Treatment of human platelet-rich plasma with hexahydrocurcumin resulted in an inhibitory effect on platelet aggregation, suggesting the potential of this compound as an anti-atherosclerogenic agent in humans.
Subject(s)
Curcumin/analogs & derivatives , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation/drug effects , Curcumin/chemistry , Curcumin/pharmacology , Humans , Molecular Structure , Platelet Aggregation Inhibitors/chemistryABSTRACT
Endotoxemia causes several hematological dysfunctions, including platelet degranulation or disseminated intravascular coagulation, which lead to thrombotic and hemorrhagic events. Here, we tested the hypothesis that bacterial lipopolysaccharide (LPS)-stimulated leukocytes contribute to platelet aggregative dysfunction, and this function is attenuated by antioxidants. Platelet-rich plasma (PRP) was prepared from whole blood of normal and endotoxemic rats. The ability of platelet aggregation was measured by an aggregometer. LPS (50-100 µg/mL) was incubated with PRP, whole blood and PRP with polymorphonuclear leukocytes (PMNs) for 30 minutes, 60 minutes and 90 minutes, and platelet aggregation was detected. LPS-induced platelet aggregative dysfunction was undetectable in intact PRP which was isolated from normal whole blood, whereas it was detected in PRP isolated from endotoxemic rats and LPS-treated whole blood. Moreover, the effect of LPS-induced platelet aggregative dysfunction on intact PRP was observed when the PMNs were added. LPS-induced platelet aggregative dysfunction was significantly attenuated by catalase alone and in combination with N(G)-nitro-L-arginine methyl ester, but not by N(G)-nitro-L-arginine methyl ester alone. These results indicate that LPS-stimulated PMNs modulate platelet aggregation during LPS treatment and the effects are reversed by antioxidants. PMNs serve as an approach to understand LPS-induced platelet aggregative dysfunction during endotoxemia. During this process, the generation of reactive oxygen species, hydrogen peroxide especially, from LPS-stimulated PMNs could be an important potential factor in LPS-induced platelet aggregative dysfunction. Catalase contributes to the prevention of platelet dysfunction during LPS-induced sepsis.