Selenium, glutathione peroxidase, peroxides and platelet functions.

In the last five years, there has been a renewal of interest in the protective role of selenium in vascular disorders, inspired by experimental evidence that this trace element could modulate leukotriene and prostaglandin synthesis in both endothelial cells and platelets. In people living in low-selenium areas, a relationship has been established between a decrease in plasma selenium and an increase in the risk of coronary disease, atherosclerosis, platelet hyperaggregability and synthesis of proaggregant and proinflammatory compounds like thromboxane A(2) and leukotrienes. Selenium, as an essential part of glutathione peroxidase, takes parr in the I eduction of hydrogen peroxides and lipid peroxides. The concentration of these peroxides, in turn, regulates the activities of cyclooxygenase and lipoxygenase pathways, ultimately influencing the production of eicosanoids and modulating the balance between a proaggregatory and antiaggregatory state. Recent evidence shows that selenium, via its action on glutathione peroxidase activity, may be primarily responsible for the regulation of the endogenous hydroperoxide level. In human platelets, the activity of glutathione peroxidase is particularly high and is very sensitive to the requirement of selenium. This sensitivity could explain why platelets of selenium-deficient subjects show increased aggregation, thromboxane B-2 production and synthesis of the lipoxygenase-derived compounds. In these deficient subjects, selenium administration increases platelet glutathione peroxidase activity and inhibits platelet hyperaggregation and leukotriene synthesis. These results support the hypothesis that selenium supplementation has a positive effect on platelet aggregation in selenium-deficient subjects, In France, more than 10% of the population is selenium-deficient and long-term supplementation with low doses of selenium could have a beneficial effect on the prevention of both thrombosis and coronary heart disease in these subjects.