Eligini Sonia, Munno Marco, Atlas Daphne, Banfi Cristina
Centro Cardiologico Monzino IRCCS, Unit of Functional Proteomics, Metabolomics, and Network Analysis, 20138 Milan, Italy.
Department of Biological Chemistry, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Antioxidants (Basel). 2023 Jul 7;12(7):1395. doi: 10.3390/antiox12071395.
In the present study, we tested the effect of small-molecular-weight redox molecules on collagen-induced platelet aggregation. We used N-acetylcysteine amide (AD4/NACA), the amide form of N-acetylcysteine (NAC), a thiol antioxidant with improved lipophilicity and bioavailability compared to NAC, and the thioredoxin-mimetic (TXM) peptides, TXM-CB3, TXM-CB13, and TXM-CB30. All compounds significantly inhibited platelet aggregation induced by collagen, with TXM-peptides and AD4 being more effective than NAC. The levels of TxB and 12-HETE, the main metabolites derived from the cyclooxygenase and lipoxygenase pathways following platelet activation, were significantly reduced in the presence of AD4, TXM peptides, or NAC, when tested at the highest concentration (0.6 mM). The effects of AD4, TXM-peptides, and NAC were also tested on the clotting time (CT) of whole blood. TXM-CB3 and TXM-CB30 showed the greatest increase in CT. Furthermore, two representative compounds, TXM-CB3 and NAC, showed an increase in the anti-oxidant free sulfhydryl groups of plasma detected via Ellman's method, suggesting a contribution of plasma factors to the antiaggregating effects. Our results suggest that these small-molecular-weight redox peptides might become useful for the prevention and/or treatment of oxidative stress conditions associated with platelet activation.
在本研究中，我们测试了小分子氧化还原分子对胶原蛋白诱导的血小板聚集的影响。我们使用了N-乙酰半胱氨酸酰胺（AD4/NACA），即N-乙酰半胱氨酸（NAC）的酰胺形式，与NAC相比，它是一种具有改善的亲脂性和生物利用度的硫醇抗氧化剂，以及硫氧还蛋白模拟（TXM）肽TXM-CB3、TXM-CB13和TXM-CB30。所有化合物均显著抑制胶原蛋白诱导的血小板聚集，其中TXM肽和AD4比NAC更有效。当在最高浓度（0.6 mM）下测试时，在AD4、TXM肽或NAC存在的情况下，血小板活化后源自环氧合酶和脂氧合酶途径的主要代谢产物TxB和12-HETE的水平显著降低。还测试了AD4、TXM肽和NAC对全血凝血时间（CT）的影响。TXM-CB3和TXM-CB30显示CT增加最大。此外，两种代表性化合物TXM-CB3和NAC通过埃尔曼法检测到血浆中抗氧化游离巯基增加，表明血浆因子对抗聚集作用有贡献。我们的结果表明，这些小分子氧化还原肽可能对预防和/或治疗与血小板活化相关的氧化应激状况有用。
