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  • Title: Sesamol induces apoptosis in human platelets via reactive oxygen species-mediated mitochondrial damage.
    Author: Thushara RM, Hemshekhar M, Sunitha K, Kumar MS, Naveen S, Kemparaju K, Girish KS.
    Journal: Biochimie; 2013 Nov; 95(11):2060-8. PubMed ID: 23933095.
    Abstract:
    Platelets play an indispensable role in human health and disease. Platelets are very sensitive to oxidative stress, as it leads to the damage of mitochondrial DNA, which is the initial step of a sequence of events culminating in the cell death through the intrinsic pathway of apoptosis. Owing to a lot of reports on secondary complications arising from oxidative stress caused by therapeutic drug overdose, the present study concentrated on the influence of sesamol on oxidative stress-induced platelet apoptosis. Sesamol, a phenolic derivative present in sesame seeds is an exceptionally promising drug with lots of reports on its protective functions, including its inhibitory effects on platelet aggregation at concentrations below 100 μM, and its anti-cancer effect at 1 mM. However, the present study explored the toxic effects of sesamol on human platelets. Sesamol at the concentration of 0.25 mM and above induced platelet apoptosis through endogenous generation of ROS, depletion of thiol pool, and Ca(2+) mobilization. It also induced mitochondrial membrane potential depolarization, caspase activation, cytochrome c translocation and phosphatidylserine exposure, thus illustrating the pro-apoptotic effect of sesamol at higher concentration. However, even at high concentration of 2 mM sesamol effectively inhibited collagen/ADP/epinephrine-induced platelet aggregation. The study demonstrates that even though sesamol inhibits platelet aggregation, it has the tendency to elicit platelet apoptosis at higher concentrations. Sesamol has a potential as thrombolytic agent, nevertheless the current work highlights the significance of an appropriate dosage of sesamol when it is used as a therapeutic drug.
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