Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

N-acetylcysteine Amide AD4 and Thioredoxin Mimetic Peptides Inhibit Platelet Aggregation and Protect from Oxidative Stress

Version 1 : Received: 20 June 2023 / Approved: 21 June 2023 / Online: 21 June 2023 (10:56:56 CEST)

A peer-reviewed article of this Preprint also exists.

Eligini, S.; Munno, M.; Atlas, D.; Banfi, C. N-acetylcysteine Amide AD4/NACA and Thioredoxin Mimetic Peptides Inhibit Platelet Aggregation and Protect against Oxidative Stress. Antioxidants 2023, 12, 1395. Eligini, S.; Munno, M.; Atlas, D.; Banfi, C. N-acetylcysteine Amide AD4/NACA and Thioredoxin Mimetic Peptides Inhibit Platelet Aggregation and Protect against Oxidative Stress. Antioxidants 2023, 12, 1395.

Abstract

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), the amide form of N-acetylcysteine (NAC), a thiol antioxidant with improved lipophilicity and bio-availability compared to NAC, and the thioredoxin mimetics (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 TxB2 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 effect of AD4, TXM-peptides, and NAC was tested also on the clotting time (CT) of whole blood. TXM-CB3 and TXM-CB30 showed the highest increase of CT. Furthermore, two representative compounds, TXM-CB3, and NAC, showed an increase in the an-ti-oxidant free sulfhydryl groups of plasma detected by 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.

Keywords

platelet; aggregation; N-acetylcysteine; N-acetylcysteine amide; thioredoxin mimetic peptides; clotting time; TxB2; 12-HETE

Subject

Medicine and Pharmacology, Cardiac and Cardiovascular Systems

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