Boland T1, Murphy D2, Reddy E2, O’Neill S2

Author affiliations
1RCSI medical student
2Department of Molecular and Cellular Therapeutics, RCSI

Royal College of Surgeons in Ireland Student Medical Journal 2011;4(1):96.

RCSI Alumni funded


Oxidative stress is associated with disturbances in the redox environment of plasma, which potentially affects platelet reactivity, in turn leading to thrombus formation. Although oxidative stress has been shown to play an integral role in the pathogenesis of diseases such as atherosclerosis and diabetes, the role of anti-oxidants in vascular disease prevention is still unclear.1,2 Although ascorbic acid (vitamin C) is a known anti-oxidant, there is limited information available regarding the impact of ascorbic acid on platelet function in vitro. This investigation is crucial in order to establish mechanisms of action and target sites of anti-oxidants. The focus of this study is to investigate the effects of ascorbic acid on platelet reactivity as indicated by platelet aggregation.


Platelets were activated using various platelet agonists known to cause platelet aggregation – collagen, thrombin receptor-activating peptide (TRAP), adenosine diphosphate (ADP) and convulxin. Both ‘pro-oxidant’ and ‘anti-oxidant’ concentrations of ascorbic acid were used. N-acetyl cysteine (NAC), a known dietary anti-oxidant supplement and pharmaceutical drug, was also tested. The external redox environment of the platelets was altered by combining ratios of both NAC and cysteine (Cys) with cystine (CySS) to form a spectrum of redox couples (NAC/CySS and Cys/CySS) from reducing to oxidising potentials. A platelet aggregometer was used to measure the degree of aggregation.


The data showed that the anti-oxidants ascorbic acid (45μm), NAC (45μm) and cysteine (45μm) inhibited platelet aggregation when platelets were activated with collagen, but not with TRAP or ADP. The reducing NAC/CySS and Cys/CySS redox potentials significantly inhibited platelet aggregation to collagen (p<0.0001), but not to convulxin.


Platelet aggregation is only inhibited when platelets are activated with collagen. Therefore, it appears that the anti-oxidants and redox couples with reducing redox potentials exert a direct effect on the collagen pathway, leading to inhibition of platelet aggregation. We suggest that this is occurring through a modification of integrin α2β1, a collagen-only receptor on the platelet surface. Collagen is a naturally occurring protein in the body, which acts as a potent platelet activator.
Further understanding of the mechanism by which collagen-mediated activation is modulated could aid in the development of novel anti-thrombotic drugs.


This work was kindly supported by a grant from the RCSI Alumni Fund.


  1. Freedman JE. Oxidative stress and platelets. Arterioscler Thromb Vasc Biol. 2008;28(3):s11-6.
  2. Madamanchi NR, Vendrov A, Runge MS. Oxidative stress and vascular disease. Arterioscler Thromb Vasc Biol. 2005;25(1):29-38.

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