CISPLATIN-INDUCED CHANGES IN BIOLOGICAL-ACTIVITY OF BLOOD-PLATELETS -THIOL-RELATED MECHANISMS

The effects of cisplatin (cis-diamminedichloroplatinum(II), CDDP) and transplatin (trans-diamminedichloroplatinum(II), TDDP), and their comp lexes with glutathione (GS-Pt) in vitro on oxygen free radical generat ion (O-2(-.)), lipid peroxidation and ADP-induced aggregation in pig b lood platelets were studied, Incubation of pig blood platelets with ci splatin or transplatin caused a loss of both protein -SH and the thiol groups of GSH. In pig blood platelets exposed to cisplatin or transpl atin (20 mu M) the GS-Pt complex was formed as a major metabolite, The formation of GS-Pt complexes in platelet cytosol was time dependent a nd the intracellular content of this complex reached a maximal level a fter 24 h, GS-Pt complexes were found to induce platelet lipid peroxid ation, measured as thiobarbituric acid reactive substance level, and 0 (2)(-.) generation, and it was more active than cisplatin or transplat in alone. Cisplatin and its GS-Pt complex had an inhibitory effect on ADP-induced platelet aggregation. These results showed that GS-Pt comp lexes affect platelet metabolism and function. It seems that glutathio ne-associated metabolism of platinum compounds plays an important role in the cytotoxicity and biological activity of these drugs.