The role of oxidative stress in the initiation and progression of myelodysplastic syndromes (MDS) as a consequence of iron overload remains unclear. In this study we have simultaneously quantified plasma low-molecular-weight aminothiols, malondialdehyde, nitrite, and nitrate and have studied their correlation with serum iron/ferritin levels, patient treatment (chelation therapy), and clinical outcomes. We found significantly elevated plasma levels of total, oxidized, and reduced forms of cysteine (P < 0.001), homocysteine (P < 0.001), and cysteinylglycine (P < 0.006) and significantly depressed levels of total and oxidized forms of glutathione (P < 0.03) and nitrite (P < 0.001) in MDS patients compared to healthy donors. Moreover, total (P < 0.032) and oxidized cysteinylglycine (P = 0.029) and nitrite (P = 0.021) differed significantly between the analyzed MDS subgroups with different clinical classifications. Malondialdehyde levels in plasma correlated moderately with both serum ferritin levels (r = 0.78, P = 0.001) and serum free iron levels (r = 0.60, P = 0.001) and were significantly higher in patients with iron overload. The other analyzed compounds lacked correlation with iron overload (represented by serum iron/ferritin levels). For the first time our results have revealed significant differences in the concentrations of plasma aminothiols in MDS patients, when compared to healthy donors. We found no correlation of these parameters with iron overload and suggest the role of oxidative stress in the development of MDS disease.

• MeSH
• Dipeptides blood   MeSH
• Nitrates blood   MeSH
• Nitrites blood   MeSH
• Ferritins blood   MeSH
• Humans MeSH
• Malondialdehyde blood   MeSH
• Myelodysplastic Syndromes blood   complications   pathology   MeSH
• Oxidation-Reduction MeSH
• Oxidative Stress MeSH
• Iron Overload blood   complications   pathology   MeSH
• Case-Control Studies MeSH
• Sulfhydryl Compounds blood   MeSH
• Treatment Outcome MeSH
• Iron blood   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• cysteinylglycine MeSH Browser
• Dipeptides MeSH
• Nitrates MeSH
• Nitrites MeSH
• Ferritins MeSH
• Malondialdehyde MeSH
• Sulfhydryl Compounds MeSH
• Iron MeSH

The role of platelets in hemostasis may be influenced by alteration of the platelet redox state-the presence of antioxidants and the formation of reactive oxygen and nitrogen species. We investigated the effects of two antioxidants, resveratrol and trolox, on platelet activation. Trolox and resveratrol inhibited aggregation of washed platelets and platelet-rich plasma activated by ADP, collagen, and thrombin receptor-activating peptide. Resveratrol was a more effective agent in reducing platelet static and dynamic adhesion in comparison with trolox. The antioxidant capacity of resveratrol was, however, the same as that of trolox. After incubation of platelets with antioxidants, the resveratrol intraplatelet concentration was about five times lower than the intracellular concentration of trolox. Although both antioxidants comparably lowered hydroxyl radical and malondialdehyde production in platelets stimulated with collagen, TxB(2) levels were decreased by resveratrol much more effectively than by trolox. Cyclooxygenase 1 was inhibited by resveratrol and not by trolox. Our data indicate that antioxidants, apart from nonspecific redox or radical-quenching mechanisms, inhibit platelet activation also by specific interaction with target proteins. The results also show the importance of studying platelet activation under conditions of real blood flow in contact with reactive surfaces, e.g., using dynamic adhesion experiments.

• MeSH
• Platelet Aggregation drug effects   physiology   MeSH
• Antioxidants pharmacology   MeSH
• Cell Adhesion drug effects   physiology   MeSH
• Chromans pharmacology   MeSH
• Cyclooxygenase 1 metabolism   MeSH
• Hemostasis drug effects   MeSH
• Collagen pharmacology   MeSH
• Cells, Cultured MeSH
• Humans MeSH
• Malondialdehyde metabolism   MeSH
• Resveratrol MeSH
• Stilbenes pharmacology   MeSH
• Thromboxane B2 metabolism   MeSH
• Blood Platelets drug effects   physiology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Names of Substances
• 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid MeSH Browser
• Antioxidants MeSH
• Chromans MeSH
• Cyclooxygenase 1 MeSH
• Collagen MeSH
• Malondialdehyde MeSH
• Resveratrol MeSH
• Stilbenes MeSH
• Thromboxane B2 MeSH