Effect of compounds causing reversible perturbation of the cellular thiol-disulfide status on the aggregation of human blood platelets

Abstract

Diamide, cumene hydroperoxide, t-butyl hydroperoxide and divicine are compounds which cause a reversible oxidation of cellular SH groups. They influence the aggregation of human platelets in a common manner when added to platelet rich plasma, simultaneously with different types of aggregation inducer: (1) The initial phase of aggregation becomes accelerated. This is accompanied by a more sensitive response to the inducer. (2) The aggregation becomes reversible. The accelerated initial phase of aggregation is followed by a switchover to deaggregation. Addition of diamide to platelet suspensions results in an immediate and fast diminution of the platelet GSH level. Extent and duration of the GSH fall depend on the diamide concentration used. The time courses found for the platelet GSH level suggest a causal connection with the altered aggregation response. Therefore, the conclusion is drawn that perturbation of the cellular thiol-disulfide status influences a fundamental and common part of the platelet activation sequence.