The protective effects of resveratrol against changes in blood platelet thiols induced by platinum compounds.
Cisplatin (cis-diamminedichloroplatinum II, cisPt) is especially useful in the treatment of epithelial malignancies, however, the use of cisplatin is accompanied by several toxicities including haematological toxicity. Contrary to cisplatin, selenium-cisplatin conjugate ((NH(3))(2)Pt(SeO(3)); Se-Pt) has only a slight toxicity effect on blood platelet function. In the mechanism of platinum compounds action on platelets thiols are involved. The aim of the present studies was to examine in vitro how trans-resveratrol (trans-3,4',5-trihydroxystilbene) acts on the levels of platelet glutathione (GSH) and other thiol-containing compounds and how, as an antioxidant, protecs blood platelets against the oxidative stress caused by platinum compounds (cisPt and Se-Pt). To analyse the level of thiols in human blood platelets treated with platinum compounds and with resveratrol the classical technique HPLC has been used. Blood platelets isolated by differential centrifugation of human blood were incubated (30 min, 37 degrees C) with cisPt or Se-Pt at dose of 10 microg/ml that inhibits platelet function and with resveratrol (25 microg/ml). The obtained results indicate that platinum compounds caused in platelets a decrease of both, reduced glutathione (GSH) and free thiols of cysteine (CSH) and cysteinylglycine (CGSH). The pool of these compounds in unreduced form was increased. Platinum compounds caused the reduction of platelet protein thiols. Resveratrol (after 30 min action) at the concentration of 25 microg/ml partly reduced the platinum compounds induced decrease of platelet thiols, particularly thiols in acid-soluble fraction.
Olas
B
B
Department of General Biochemistry, University of Lodz, Lodz, Poland. olasb@biol.uni.lodz.pl
Wachowicz
B
B
Bald
E
E
Głowacki
R
R
D000975:Antioxidants / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002945:Cisplatin / Q000633:toxicity*; D003545:Cysteine / Q000378:metabolism; D004151:Dipeptides / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D018384:Oxidative Stress / Q000187:drug effects*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D000975:Antioxidants; D004151:Dipeptides; D013267:Stilbenes; D013438:Sulfhydryl Compounds; C028505:cysteinylglycine; D005978:Glutathione; D003545:Cysteine; D002945:Cisplatin; D000077185:Resveratrol