N-acetylcysteine Amide AD4/NACA and Thioredoxin Mimetic Peptides Inhibit Platelet Aggregation and Protect against Oxidative Stress

In the present study, we tested effect of small-molecular-weight redox molecules on collagen-induced platelet aggregation. We used N-acetylcysteine amide (AD4/NACA), form (NAC), a thiol antioxidant with improved lipophilicity and bioavailability compared to NAC, thioredoxin-mimetic (TXM) peptides, TXM-CB3, TXM-CB13, TXM-CB30. All compounds significantly inhibited aggregation induced by collagen, TXM-peptides AD4 being more effective than NAC. The levels TxB2 12-HETE, main metabolites derived from cyclooxygenase lipoxygenase pathways following activation, were reduced in presence AD4, TXM or when at highest concentration (0.6 mM). effects TXM-peptides, NAC also clotting time (CT) whole blood. TXM-CB3 TXM-CB30 showed greatest increase CT. Furthermore, two representative compounds, an anti-oxidant free sulfhydryl groups plasma detected via Ellman’s method, suggesting contribution factors antiaggregating effects. Our results suggest that these peptides might become useful for prevention and/or treatment oxidative stress conditions associated activation.