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ID 110054
Title Alternative
ホルボール12-ミリスタート 13-アセタート分化誘導による巨核球系細胞を用いた血小板機能に対する各種薬剤効果の評価
Effects of various drugs on platelet functions
Author
Tada, Tomoki Tokushima University
Oboshi, Wataru Kagawa Prefectural University of Health Sciences
Keywords
platelets
intracellular Ca2+ concentration ([Ca2+]i)
aspirin
cilostazol
ibuprofen
sodium valproate
Content Type
Thesis or Dissertation
Description
Background: The hyperfunction and activation of platelets have been strongly implicated in the development and recurrence of arterial occlusive disease, and various antiplatelet drugs are used to treat and prevent such diseases. New antiplatelet drugs and many other drugs have been developed, but some drugs may have adverse effects on platelet functions.
Objective: The aim of this study was to establish an evaluation method for evaluating the effect and adverse effect of various drugs on platelet functions.
Materials and methods: Human erythroid leukemia (HEL) cells were used after megakaryocytic differentiation with phorbol 12-myristate 13-acetate as an alternative to platelets. Drugs were evaluated by changes in intracellular Ca2+ concentration ([Ca2+]i) mobilization in Fura2-loaded phorbol 12-myristate 13-acetate-induced HEL cells. Aspirin and cilostazol were selected as antiplatelet drugs and ibuprofen and sodium valproate as other drugs.
Results: There was a positive correlation between [Ca2+]i and platelet aggregation induced by thrombin. Aspirin (5.6–560 µM) and cilostazol (5–10 µM) significantly inhibited thrombin-induced increases in [Ca2+]i in a concentration-dependent manner. On the other hand, ibuprofen (8–200 µM) and sodium valproate (50–1,000 µg/mL) also significantly inhibited thrombin-induced increases in [Ca2+]i in a concentration-dependent manner. Furthermore, the interaction effects of the simultaneous combined use of aspirin and ibuprofen or sodium valproate were evaluated. When the inhibitory effect of aspirin was higher than that of ibuprofen, the effect of aspirin was reduced, whereas when the inhibitory effect of aspirin was lower than that of ibuprofen, the effect of ibuprofen was reduced. The combination of aspirin and sodium valproate synergistically inhibited thrombin-induced [Ca2+]i.
Conclusion: It is possible to induce HEL cells to differentiate into megakaryocytes, which are a useful model for the study of platelet functions, and the quantification of the inhibition of thrombin-induced increases in [Ca2+]i is applicable to the evaluation of the effects of various drugs on platelets.
Journal Title
Drug Design, Development and Therapy
ISSN
11778881
Publisher
Dove Press
Volume
10
Start Page
3099
End Page
3107
Published Date
2016-09-26
Remark
内容要旨・審査要旨・論文本文の公開:
内容要旨 : LID201704181007.pdf
審査要旨 : LID201704181008.pdf
論文本文 : LID201704181009.pdf
本論文は, 著者Tomoki Tadaの学位論文として提出され, 学位審査・授与の対象となっている。
Rights
Copyrihgt© 2016 Tada et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php
and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php)
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3037号
Diploma Number
甲保第30号
Granted Date
2017-03-23
Degree Name
Doctor of Health Science
Grantor
Tokushima University
departments
Medical Sciences
Pharmaceutical Sciences