In vitro effect of reduced glutathione on platelet function.
BACKGROUND
Generation of reactive oxygen species has been suggested to represent an important regulatory mechanism of platelet reactivity in both physiological and pathological conditions, and free-radical scavengers may inhibit platelet activation. The purpose of the present study was to investigate the effect of reduced glutathione (GSH) on different platelet functions stimulated by ADP, collagen or PAF.


METHODS
Platelet aggregation was investigated by Born's method. TxB2 and PDGF levels were measured by radioimmunoassay.


RESULTS
GSH at the lowest dose (1 mM) did not significantly modify aggregation, TxB2 production or PDGF release induced by ADP or PAF, while at higher concentrations (3 mM or 10 mM) it significantly inhibited all parameters. Collagen-induced platelet activation was remarkably less sensitive to GSH, since aggregation was not significantly reduced, while TxB2 production was reduced by GSH when employed at concentrations of 3 mM or 10 mM, and PDGF release was inhibited only by the highest dose (10 mM). IC50 for inhibition of platelet aggregation, TxB2 production and PDGF release 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 16.30 mM when collagen was the agonist.


CONCLUSIONS
Our data suggest that GSH may act as a physiological inhibitor of platelet activation and may therefore contribute to the regulation of platelet reactivity.
Pacchiarini
L
L
Department of Internal Medicine, University of Pavia, IRCCS Policlinico San Matteo, Italy.
Tua
A
A
Grignani
G
G
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D003094:Collagen / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D010084:Oxidation-Reduction; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000032:analysis; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013929:Thromboxane B2 / Q000097:blood
D010975:Platelet Aggregation Inhibitors; D010982:Platelet-Derived Growth Factor; D017382:Reactive Oxygen Species; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; D003094:Collagen; D005978:Glutathione