Modulation of cisplatin toxicity in blood platelets by glutathione depletion.
The effect of a specific inhibitor of gamma-glutamylcysteine synthetase, L-buthionine sulfoximine (BSO), on the action of cisplatin in pig blood platelets was investigated. We show that the effect of BSO, blocking glutathione (GSH) synthesis, on depletion of GSH level in platelets was time and dose dependent (p<0.05). Exposure of blood platelets to BSO reduced not only the cellular GSH content, but diminished also cytotoxicity effects of cisplatin on platelets. Cytotoxic effects of cisplatin were determined by the extent of oxidative stress in these cells, i.e. lipid peroxidation expressed as thiobarbituric acid reactive substances and oxygen free radicals (superoxide anion). The obtained results confirm that the intracellular level of GSH plays an important role in the action of cisplatin on blood platelets.
Olas
B
B
Department of General Biochemistry, Institute of Biochemistry, University of Lódz, Poland.
Wachowicz
B
B
D000818:Animals; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors / Q000633:toxicity*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D019328:Buthionine Sulfoximine / Q000008:administration & dosage / Q000494:pharmacology; D002945:Cisplatin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005978:Glutathione / Q000172:deficiency* / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013552:Swine; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D019328:Buthionine Sulfoximine; D005978:Glutathione; D002945:Cisplatin