MODULATION OF CISPLATIN TOXICITY IN BLOOD-PLATELETS BY GLUTATHIONE DEPLETION

The effect of a specific inhibitor of gamma-glutamylcysteine synthetas e, L-buthionine sulfoximine (BSO), on the action of cisplatin in pig b lood platelets was investigated. We show that the effect of BSO, block ing glutathione (GSH) synthesis, on depletion of GSH level in platelet s was time and dose dependent (p<0.05). Exposure of blood platelets to BSO reduced not only the cellular GSH content, but diminished also cy totoxicity effects of cisplatin on platelets. Cytotoxic effects of cis platin were determined by the extent of oxidative stress in these cell s, i.e. lipid peroxidation expressed as thiobarbituric acid reactive s ubstances and oxygen free radicals (superoxide anion). The obtained re sults confirm that the intracellular level of GSH plays an important r ole in the action of cisplatin on blood platelets. [(C) 1998 Lippincot t-Raven Publishers.].