INHIBITORY EFFECTS OF CISPLATIN AND ITS CONJUGATE WITH GLUTATHIONE ONBLOOD-PLATELET ACTIVITY

Cisplatin (cis-diamminedichloroplatinum II, CDDP) is a widely used che motherapeutic agent; however, its haematological toxicity may become a n important dose-limiting factor, The aim of the present study was to evaluate the effects of cisplatin and its metabolite with glutathione (GS-Pt conjugate) on thrombin - induced platelet aggregation, the secr etory process and the arachidonate pathway in vitro, Pre-treatment of platelets with GS-Pt conjugate (60 min, 20 mu M) but not with cisplati n alone, caused inhibition of thrombin-induced platelet aggregation, G S-Pt conjugate had also a strong inhibitory effect on the release of p roteins and adenine nucleotides from platelet granules, After pre-incu bation of platelets with cisplatin and its conjugate, we observed in t hrombin-activated platelets, a decreased amount of malonyldialdehyde ( a marker of thromboxane A(2) synthesis), We suggest that arachidonate metabolism plays an important role in determining the cytotoxicity of cisplatin.