Inhibitory activity of kinetin on free radical formation of activated platelets in vitro and on thrombus formation in vivo

George Hsiao, Ming Yi Shen, Kuan Hung Lin, Chin Yi Chou, Nien Hsuan Tzu, Chien Huang Lin, Duen Suey Chou, Tzeng-Fu Chen, Joen Rong Sheu

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Kinetin has been shown to have anti-aging effects on several different systems, including plants and human cells. Recently, we demonstrated that kinetin markedly inhibited platelet aggregation in washed human platelets. In the present study, an electron spin resonance (ESR) method was used to further evaluate the scavenging activity of kinetin on the free radicals formed. Kinetin (70 and 150 μM) concentration dependently reduced the ESR signal intensity of hydroxyl radicals in collagen (1 μg/ml)-activated platelets. Furthermore, kinetin was effective in reducing the mortality of ADP-induced acute pulmonary thromboembolism in mice when administered intravenously at doses of 4 and 6 mg/kg. In addition, intravenous injection of kinetin (4 and 6 mg/kg) significantly prolonged the bleeding time by approximately 1.9- and 2.1-fold as compared with normal saline in severed mesenteric arteries of rats. A continuous infusion of kinetin (0.6 mg/kg/min) for 10 min also significantly increased the bleeding time by about 2.3-fold, and the bleeding time returned to baseline within 120 min after cessation of kinetin infusion. Platelet thrombi formation was induced by irradiation of mesenteric venules with filtered light in mice pretreated intravenously with fluorescein sodium. When kinetin was administered at 13 and 14 mg/kg in mice pretreated with fluorescein sodium (5 mg/kg), the occlusion time was significantly prolonged. In conclusion, these results suggest that kinetin has effective free radical-scavenging activity in vitro and antithrombotic activity in vivo. Treatment with kinetin may lower the risk of thromboembolic-related disorders. Therefore, kinetin may be a potential therapeutic agent for arterial thrombosis, but its toxicity must be further assessed.

Original languageEnglish
Pages (from-to)281-287
Number of pages7
JournalEuropean Journal of Pharmacology
Volume465
Issue number3
DOIs
Publication statusPublished - Apr 4 2003

Fingerprint

Kinetin
Free Radicals
Thrombosis
Blood Platelets
Bleeding Time
Electron Spin Resonance Spectroscopy
Fluorescein
In Vitro Techniques
Mesenteric Arteries
Venules
Plant Cells
Pulmonary Embolism
Platelet Aggregation
Intravenous Injections
Hydroxyl Radical
Adenosine Diphosphate

Keywords

  • Arterial thrombosis
  • Bleeding time
  • Hydroxyl radical
  • Kinetin
  • Occlusion time

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Inhibitory activity of kinetin on free radical formation of activated platelets in vitro and on thrombus formation in vivo. / Hsiao, George; Shen, Ming Yi; Lin, Kuan Hung; Chou, Chin Yi; Tzu, Nien Hsuan; Lin, Chien Huang; Chou, Duen Suey; Chen, Tzeng-Fu; Sheu, Joen Rong.

In: European Journal of Pharmacology, Vol. 465, No. 3, 04.04.2003, p. 281-287.

Research output: Contribution to journalArticle

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abstract = "Kinetin has been shown to have anti-aging effects on several different systems, including plants and human cells. Recently, we demonstrated that kinetin markedly inhibited platelet aggregation in washed human platelets. In the present study, an electron spin resonance (ESR) method was used to further evaluate the scavenging activity of kinetin on the free radicals formed. Kinetin (70 and 150 μM) concentration dependently reduced the ESR signal intensity of hydroxyl radicals in collagen (1 μg/ml)-activated platelets. Furthermore, kinetin was effective in reducing the mortality of ADP-induced acute pulmonary thromboembolism in mice when administered intravenously at doses of 4 and 6 mg/kg. In addition, intravenous injection of kinetin (4 and 6 mg/kg) significantly prolonged the bleeding time by approximately 1.9- and 2.1-fold as compared with normal saline in severed mesenteric arteries of rats. A continuous infusion of kinetin (0.6 mg/kg/min) for 10 min also significantly increased the bleeding time by about 2.3-fold, and the bleeding time returned to baseline within 120 min after cessation of kinetin infusion. Platelet thrombi formation was induced by irradiation of mesenteric venules with filtered light in mice pretreated intravenously with fluorescein sodium. When kinetin was administered at 13 and 14 mg/kg in mice pretreated with fluorescein sodium (5 mg/kg), the occlusion time was significantly prolonged. In conclusion, these results suggest that kinetin has effective free radical-scavenging activity in vitro and antithrombotic activity in vivo. Treatment with kinetin may lower the risk of thromboembolic-related disorders. Therefore, kinetin may be a potential therapeutic agent for arterial thrombosis, but its toxicity must be further assessed.",
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AU - Hsiao, George

AU - Shen, Ming Yi

AU - Lin, Kuan Hung

AU - Chou, Chin Yi

AU - Tzu, Nien Hsuan

AU - Lin, Chien Huang

AU - Chou, Duen Suey

AU - Chen, Tzeng-Fu

AU - Sheu, Joen Rong

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