Modification of glutathione content in platelet concentrates by the use of acivicin

Intracellular glutathione declines progressively in platelet concentrates stored for transfusion, but little is known about the nature of this process.

Acivicin, an irreversible inhibitor of gamma-glutamyl transpeptidase, was used to determine the fate of glutathione lost from platelets during storage. Glutathione, cysteinylglycine, cysteine, and their disulfides were measured by high-performance liquid chromatography.

In control and acivicin-treated platelet concentrates, intracellular glutathione declined progressively during 7 days' storage, with half-disappearance times of 2.12 +/- 0.22 and 2.13 +/- 0.23 days, respectively. No glutathione accumulated accumulated in the medium of control concentrates. In concentrates treated with acivicin, glutathione accumulated in plasma to a level equal to 150 percent of that present in platelets and plasma on Day 1 of storage, which suggested a net synthesis of glutathione during storage. The sum of glutathione, cysteinylglycine, and cysteine in plasma was not different in control and acivicin-treated concentrates; however, plasma from control concentrates contained significantly higher amounts of cysteinylglycine and cysteine. Treatment of concentrates with acivicin had a small favorable effect on plasma lactate dehydrogenase, beta-thromboglobulin, and beta-N-acetylglucosaminidase during storage.

The loss of glutathione from platelets during their storage as concentrates for transfusion is due to its egress into the suspending medium and catabolism by gamma-glutamyl transpeptidase.