Sesamol induces apoptosis in human platelets via reactive oxygen species-mediated mitochondrial damage

Thushara, R. M. and Hemshekhar, M. and Sunitha, K. and Kumar, M. S. and Naveen, S. and Kemparaju, K. and Girish, K. S. (2013) Sesamol induces apoptosis in human platelets via reactive oxygen species-mediated mitochondrial damage. Biochimie, 95 (11). pp. 2060-2068.

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Official URL: http://doi.org/10.1016/j.biochi.2013.07.032

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 Ca2+ 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.

Item Type: Article
Uncontrolled Keywords: article, human, controlled study, phenol derivative, unclassified drug, Antioxidants, oxidative stress, reactive oxygen metabolite, drug cytotoxicity, antineoplastic activity, Humans, plant seed, Oxidative Stress, Western blotting, human cell, Phenols, Reactive Oxygen Species, apoptosis, Apoptosis, thrombocyte aggregation, Mitochondrial, Platelet Aggregation, exposure, Mitochondria, mitochondrion, caspase 9, caspase 3, Caspase 3, Membrane Potential, mitochondrial membrane potential, Blood Platelets, cytochrome c, enzyme activation, phosphatidylserine, thrombocyte, Cytochromes c, Oxidative stress, Benzodioxoles, sesamol, Sesamum indicum, Caspases, Caspase 9, cell membrane depolarization, Drug overdose, fibrinolytic agent, Platelet aggregation, Platelet Aggregation Inhibitors, Platelet apoptosis, sesame, Sesamol, thrombocyte function
Subjects: C Chemical Science > Biochemistry
Divisions: Department of > Biochemistry
Depositing User: Arshiya Kousar
Date Deposited: 09 Dec 2019 10:02
Last Modified: 09 Dec 2019 10:02
URI: http://eprints.uni-mysore.ac.in/id/eprint/9536

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