IN-VITRO EFFECT OF REDUCED GLUTATHIONE ON PLATELET-FUNCTION

Background. Generation of reactive oxygen species has been suggested t o represent an important regulatory mechanism of platelet reactivity i n both physiological and pathological conditions, and free-radical sca vengers may inhibit platelet activation. The purpose of the present st udy was to investigate the effect of reduced glutathione (GSH) on diff erent platelet functions stimulated by ADP, collagen or PAF. Methods. Platelet aggregation was investigated by Born's method. TxB(2) and PDG F levels were measured by radioimmunoassay. Results. GSH at the lowest dose (1 mM) did not significantly modify aggregation, TxB(2) producti on or PDGF release induced by ADP or PAF, while at higher concentratio ns (3 mM or 10 mM) it significantly inhibited all parameters. Collagen -induced platelet activation was remarkably less sensitive to GSH, sin ce aggregation was not significantly reduced, while TxB(2) production was reduced by GSH when employed at concentrations of 3 mM or 10 mM, a nd PDGF release was inhibited only by the highest dose (10 mM). IC50 f or inhibition of platelet aggregation, TxB(2) production and PDGF rele ase were between 1.43 and 2.36 mM when platelets were stimulated with ADP, between 2.23 and 8.90 mM when PAF was used and between 8.00 and 1 6.30 mM when collagen was the agonist. Conclusions. Our data suggest t hat GSH may act as a physiological inhibitor of platelet activation an d may therefore contribute to the regulation of platelet reactivity.