Abstract

Lycopene is a natural carotenoid antioxidant that is present in tomatoes and tomato products. The pharmacologic function of lycopene in platelets is not yet understood. Therefore, in this study we sought to systematically examine the effects of lycopene in the prevention of platelet aggregation and thrombus formation. We found that lycopene concentration-dependently (2-12 μmol/L) inhibited platelet aggregation in human platelets stimulated by agonists. Lycopene (6 and 12 μmol/L) inhibited phosphoinositide breakdown in platelets labeled with tritiated inositol, intracellular Ca+2 mobilization in Fura-2 AM-loaded platelets, and thromboxane B2 formation stimulated by collagen. In addition, lycopene (6 and 12 μmol/L) significantly increased the formations of cyclic GMP and nitrate but not cyclic AMP in human platelets. Rapid phosphorylation of a protein of 47,000 Da (P47), a marker of protein kinase C activation, was triggered by PDBu (60 nmol/L). This phosphorylation was markedly inhibited by lycopene (12 μmol/L) in phosphorus-32-labeled platelets. In an in vivo study, thrombus formation was induced by irradiation of mesenteric venules in mice pretreated with fluorescein sodium. Lycopene (5, 10, and 20 mg/kg) significantly prolonged the latency period for the induction of platelet-plug formation in mesenteric venules. These results indicate that the antiplatelet activity of lycopene may involve the following pathways: (1) Lycopene may inhibit the activation of phospholipase C, followed by inhibition of phosphoinositide breakdown and thromboxane B2 formation, thereby leading to inhibition of intracellular Ca+2 mobilization. (2) Lycopene also activated the formations of cyclic GMP/nitrate in human platelets, resulting in the inhibition of platelet aggregation. The results may imply that tomato-based foods are especially beneficial in the prevention of platelet aggregation and thrombosis.

Original languageEnglish
Pages (from-to)216-226
Number of pages11
JournalJournal of Laboratory and Clinical Medicine
Volume146
Issue number4
DOIs
Publication statusPublished - Oct 2005

Fingerprint

Platelet Activation
Platelets
Thrombosis
Chemical activation
Blood Platelets
Platelet Aggregation
Lycopersicon esculentum
Agglomeration
Thromboxane B2
Venules
Phosphorylation
Cyclic GMP
Phosphatidylinositols
Nitrates
lycopene
In Vitro Techniques
Fura-2
Type C Phospholipases
Inositol
Carotenoids

ASJC Scopus subject areas

  • Medicine(all)
  • Pathology and Forensic Medicine

Cite this

Inhibitory effects of lycopene on in vitro platelet activation and in vivo prevention of thrombus formation. / Hsiao, George; Wang, Ying; Tzu, Nien Hsuan; Fong, Tsorng Hang; Shen, Ming Yi; Lin, Kuang Hung; Chou, Duen Suey; Sheu, Joen Rong.

In: Journal of Laboratory and Clinical Medicine, Vol. 146, No. 4, 10.2005, p. 216-226.

Research output: Contribution to journalArticle

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abstract = "Lycopene is a natural carotenoid antioxidant that is present in tomatoes and tomato products. The pharmacologic function of lycopene in platelets is not yet understood. Therefore, in this study we sought to systematically examine the effects of lycopene in the prevention of platelet aggregation and thrombus formation. We found that lycopene concentration-dependently (2-12 μmol/L) inhibited platelet aggregation in human platelets stimulated by agonists. Lycopene (6 and 12 μmol/L) inhibited phosphoinositide breakdown in platelets labeled with tritiated inositol, intracellular Ca+2 mobilization in Fura-2 AM-loaded platelets, and thromboxane B2 formation stimulated by collagen. In addition, lycopene (6 and 12 μmol/L) significantly increased the formations of cyclic GMP and nitrate but not cyclic AMP in human platelets. Rapid phosphorylation of a protein of 47,000 Da (P47), a marker of protein kinase C activation, was triggered by PDBu (60 nmol/L). This phosphorylation was markedly inhibited by lycopene (12 μmol/L) in phosphorus-32-labeled platelets. In an in vivo study, thrombus formation was induced by irradiation of mesenteric venules in mice pretreated with fluorescein sodium. Lycopene (5, 10, and 20 mg/kg) significantly prolonged the latency period for the induction of platelet-plug formation in mesenteric venules. These results indicate that the antiplatelet activity of lycopene may involve the following pathways: (1) Lycopene may inhibit the activation of phospholipase C, followed by inhibition of phosphoinositide breakdown and thromboxane B2 formation, thereby leading to inhibition of intracellular Ca+2 mobilization. (2) Lycopene also activated the formations of cyclic GMP/nitrate in human platelets, resulting in the inhibition of platelet aggregation. The results may imply that tomato-based foods are especially beneficial in the prevention of platelet aggregation and thrombosis.",
author = "George Hsiao and Ying Wang and Tzu, {Nien Hsuan} and Fong, {Tsorng Hang} and Shen, {Ming Yi} and Lin, {Kuang Hung} and Chou, {Duen Suey} and Sheu, {Joen Rong}",
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T1 - Inhibitory effects of lycopene on in vitro platelet activation and in vivo prevention of thrombus formation

AU - Hsiao, George

AU - Wang, Ying

AU - Tzu, Nien Hsuan

AU - Fong, Tsorng Hang

AU - Shen, Ming Yi

AU - Lin, Kuang Hung

AU - Chou, Duen Suey

AU - Sheu, Joen Rong

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