Effects of cadmium treatment in vitro on the antioxidant protection mechanism and activation of human blood platelets.

ABSTRACT

Interactions of human platelets with cadmium in vitro were studied with respect to the platelet activation process as indicated by malondialdehyde (MDA) formation and also to the components of the cellular antioxidant defence system such as catalase, glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), glucose-6-phosphate dehydrogenase (G6PDH), and reduced glutathione (GSH). Cadmium treatment stimulated platelet MDA formation after a lag phase of at least 15 min and this effect was completely blocked by either 1 mM aspirin or 1 mM CaCl2. Cadmium pretreated platelets also displayed a much higher (5 fold) MDA formation when stimulated by thrombin. Platelet catalase activity was decreased by almost 50% after incubation with cadmium. There was also a moderate decline in platelet GSH and GR activity along with a stimulation of GST and G6PDH activity. These results suggest (1) the cadmium effect on platelets as observed by enhanced formation of MDA via the cyclooxygenase pathway involves intraplatelet accumulation of cadmium which is inhibited by calcium, (2) a modest decline in GSH, presumably due to the inadequacy of H2O2 detoxification mechanism, does not adversely affect platelet function because of the adaptive response of G6PDH, and (3) intracellular accumulation of cadmium may result in platelet hyperactivity through higher intraplatelet free calcium levels resulting directly through cadmium action or indirectly through higher H2O2 levels due to catalase inhibition.