대한의생명과학회지 (Biomedical Science Letters)

  • 제20권2호
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  • Pages.70-76
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  • 2014
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  • 1738-3226(pISSN)
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  • 2288-7415(eISSN)
대한의생명과학회 (The Korean Society for Biomedical Laboratory Sciences)
권호 표지

Anti-platelet Effects of Dimethyl Sulfoxide via Down-regulation of COX-1 and $TXA_2$ Synthase Activity in Rat Platelets

  • Ro, Ju-Ye (Department of Biomedical Laboratory Science, College of Medical Science, Konyang University) ;
  • Lee, Hui-Jin (Department of Biomedical Laboratory Science, College of Medical Science, Konyang University) ;
  • Ryu, Jin-Hyeob (Department of Microbiology and Immunology, Institute of Medical Science, Tokyo University) ;
  • Park, Hwa-Jin (Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering and Regional Research Center, Inje University) ;
  • Cho, Hyun-Jeong (Department of Biomedical Laboratory Science, College of Medical Science, Konyang University)
  • 투고 : 2014.04.16
  • 심사 : 2014.06.27
  • 발행 : 2014.06.30
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초록

In this study, we investigated the effect of DMSO, a highly dipolar organic liquid, in collagen ($5{\mu}g/ml$)-stimulated platelet aggregation. DMSO inhibited platelet aggregation at 0.5% by inhibiting production of thromboxane $A_2$ ($TXA_2$) which was associated with blocking cyclooxygenase (COX)-1 activity and $TXA_2$ synthase. In addition, DMSO significantly increased the formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP) and cyclic guanosine monophosphate (cGMP) from guanosine triphosphate (GTP). On the other hand, DMSO (0.1~0.5% concentration) did not affect the LDH release which indicates the cytotoxicity. Based on these results, DMSO has anti-platelet effect by regulation of several platelet signaling pathways, therefore we suggest that DMSO could be a novel strategy on many thrombotic disorders.

키워드

참고문헌

  1. Abe T, Takeuchi K, Takahashi N, Tsutsumi E, Taniyama Y, Abe K. Rat kidney thromboxane receptor: molecular cloning, signal transduction, and intrarenal expression localization. J Clin Invest. 1995. 96: 657-664. https://doi.org/10.1172/JCI118108
  2. Asmis L, Tanner FC, Sudano I, Luscher TF, Camici GG. DMSO inhibits human platelet activation through cyclooxygenase-1 inhibition. A novel agent for drug eluting stents? Biochem Biophys Res Commun. 2010. 391: 1629-1633. https://doi.org/10.1016/j.bbrc.2009.12.102
  3. Bardutzky J, Meng X, Bouley J, Duong TQ, Ratan R, Fisher M. Effects of intravenous dimethyl sulfoxide on ischemia evolution in a rat permanent occlusion model. J Cereb Blood Flow Metab. 2005. 25: 968-977. https://doi.org/10.1038/sj.jcbfm.9600095
  4. Basch H, Gadebusch HH. In vitro antimicrobial activity of dimethylsulfoxide. Appl Microbiol. 1968. 16: 1953-1954.
  5. Baumgartner HR, Haudenschild C. Adhesion of platelets to subendothelium. Ann N Y Acad Sci. 1972. 201: 22-36. https://doi.org/10.1111/j.1749-6632.1972.tb16285.x
  6. Bunting S, Moncada S, Vane JR. The prostacyclin--thromboxane A2 balance: pathophysiological and therapeutic implications. Br Med Bull. 1983. 39: 271-276. https://doi.org/10.1093/oxfordjournals.bmb.a071832
  7. Bush LR, Campbell WB, Buja LM, Tilton GD, Willerson JT. Effects of the selective thromboxane synthetase inhibitor dazoxiben on variations in cyclic blood flow in stenosed canine coronary arteries. Circulation. 1984. 69: 1161-1170. https://doi.org/10.1161/01.CIR.69.6.1161
  8. Camici GG, Steffel J, Akhmedov A, Schafer N, Baldinger J, Schulz U, Shojaati K, Matter CM, Yang Z, Luscher TF, Tanner FC. Dimethyl Sulfoxide Inhibits Tissue Factor Expression, Thrombus Formation, and Vascular Smooth Muscle Cell Activation: A Potential Treatment Strategy for Drug-Eluting Stents. Circulation. 2006. 114: 1512-1521. https://doi.org/10.1161/CIRCULATIONAHA.106.638460
  9. Cetin M, Eser B, Er O, Unal A, Kilic E, Patiroglu T, Coskun HS, Altinbas M, Arslan D, Ilhan O. Effects of DMSO on platelet functions and P-selectin expression during storage. Transfus Apher Sci. 2001. 24: 261-267. https://doi.org/10.1016/S1473-0502(01)00068-4
  10. Dujovny M, Rozario R, Kossovsky N, Diaz FG, Segal R. Antiplatelet effect of dimethyl sulfoxide, barbiturates, and methyl prednisolone. Ann N Y Acad Sci. 1983. 411: 234-244. https://doi.org/10.1111/j.1749-6632.1983.tb47304.x
  11. Egorin MJ, Rosen DM, Sridhara R, Sensenbrenner L, Cottler-Fox M. Plasma concentrations and pharmacokinetics of dimethylsulfoxide and its metabolites in patients undergoing peripheralblood stem-cell transplants. J Clin Oncol. 1998. 16: 610-615. https://doi.org/10.1200/JCO.1998.16.2.610
  12. Fitzgerald DJ, Roy L, Catella F, FitzGerald GA. Platelet activation in unstable coronary disease. N Engl J Med. 1986. 315: 983-989. https://doi.org/10.1056/NEJM198610163151602
  13. FitzGerald GA, Healy C, Daugherty J. Thromboxane A2 biosynthesis in human disease. Fed Proc. 1987. 46: 154-158.
  14. Gresele P, Deckmyn H, Nenci GG, Vermylen J. Thromboxane synthase inhibitors, thromboxane receptor antagonists and dual blockers in thrombotic disorders. Trends Pharmacol Sci. 1991. 12: 158-163. https://doi.org/10.1016/0165-6147(91)90533-X
  15. Halbrugge M, Friedrich C, Eigenthaler M, Schanzenbacher P, Walter U. Stoichiometric and reversible phosphorylation of a 46-kDa protein in human platelets in response to cGMP- and cAMP-elevating vasodilators. J Biol Chem. 1990. 265: 3088-3093.
  16. Hamberg M, Svensson J, Samuelsson B. Thromboxanes: a new group of biologically active compounds derived from prostaglandin endoperoxides. Proc Natl Acad Sci U S A. 1975. 72: 2994-2998. https://doi.org/10.1073/pnas.72.8.2994
  17. Kligman AM. TOpical pharmacology and toxicology of dimethyl sulfoxide-part 1. JAMA. 1965. 193: 796-804. https://doi.org/10.1001/jama.1965.03090100042010
  18. Li Z, Ajdic J, Eigenthaler M, Du X. A predominant role for cAMPdependent protein kinase in the cGMP-induced phosphorylation of vasodilator-stimulated phosphoprotein and platelet inhibition in humans. Blood. 2003. 101: 4423-4429. https://doi.org/10.1182/blood-2002-10-3210
  19. Miller OV, Johnson RA, Gorman RR. Inhibition of PGE1-stimulated cAMP accumulation in human platelets by thromboxane a2. Prostaglandins. 1977. 13: 599-609. https://doi.org/10.1016/0090-6980(77)90231-3
  20. Nossel HL, Wilner GD, LeRoy EC. Importances of polar groups for initiating blood coagulation and aggregating platelets. Nature. 1969. 221: 75-76. https://doi.org/10.1038/221075a0
  21. Paul BZS, Jin J, Kunapuli SP. Molecular Mechanism of Thromboxane A2-induced Platelet Aggregation: Essential Role for P2T AC and ${\alpha}$2areceptors. J Biol Chem. 1999. 274: 29108-29114. https://doi.org/10.1074/jbc.274.41.29108
  22. Rosenblum WI, El-Sabban F. Dimethyl sulfoxide (DMSO) and glycerol, hydroxyl radical scavengers, impair platelet aggregation within and eliminate the accompanying vasodilation of, injured mouse pial arterioles. Stroke. 1982. 13: 35-39. https://doi.org/10.1161/01.STR.13.1.35
  23. Shimizu S, Simon RP, Graham SH. Dimethylsulfoxide (DMSO) treatment reduces infarction volume after permanent focal cerebral ischemia in rats. Neurosci Lett. 1997. 239: 125-127. https://doi.org/10.1016/S0304-3940(97)00915-4
  24. Smith WL, DeWitt DL, Shimokawa T, Kraemer SA, Meade EA. Molecular basis for the inhibition of prostanoid biosynthesis by nonsteroidal anti-inflammatory agents. Stroke. 1990. 21: IV24-28. https://doi.org/10.1161/01.STR.21.1.24
  25. Vilahur G, Casani L, Badimon L. A thromboxane A2/prostaglandin H2 receptor antagonist (S18886) shows high antithrombotic efficacy in an experimental model of stent-induced thrombosis. Thromb Haemost. 2007. 98: 662-669.
  26. Wang G-R, Zhu Y, Halushka PV, Lincoln TM, Mendelsohn ME. Mechanism of platelet inhibition by nitric oxide: in vivo phosphorylation of thromboxane receptor by cyclic GMPdependent protein kinase. Proc Natl Acad Sci U S A. 1998. 95: 4888-4893. https://doi.org/10.1073/pnas.95.9.4888
  27. Wood DC, Wood J. Pharmacologic and biochemical considerations of dimethyl sulfoxide. Ann N Y Acad Sci. 1975. 243: 7-19. https://doi.org/10.1111/j.1749-6632.1975.tb25339.x
  28. Wusteman M, Rauen U, Simmonds J, Hunds N, Pegg DE. Reduction of cryoprotectant toxicity in cells in suspension by use of a sodium-free vehicle solution. Cryobiology. 2008. 56: 72-79. https://doi.org/10.1016/j.cryobiol.2007.10.178