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Mar Drugs. 2018 Aug 30;16(9). pii: E304. doi: 10.3390/md16090304.

Anticoagulant and Antithrombotic Properties of Three Structurally Correlated Sea Urchin Sulfated Glycans and Their Low-Molecular-Weight Derivatives.

Author information

1
Program of Glycobiology, Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro 21941-590, RJ, Brazil. arianaavasconcelos@gmail.com.
2
University Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, RJ, Brazil. arianaavasconcelos@gmail.com.
3
Program of Glycobiology, Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro 21941-590, RJ, Brazil. isabela.sucupira@gmail.com.
4
University Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, RJ, Brazil. isabela.sucupira@gmail.com.
5
Program of Glycobiology, Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro 21941-590, RJ, Brazil. alessandra.guedes@bioqmed.ufrj.br.
6
Department of Clinical Analyses and Toxicology, School of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro 21941-599, RJ, Brazil. alessandra.guedes@bioqmed.ufrj.br.
7
Program of Glycobiology, Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro 21941-590, RJ, Brazil. mael.nilo@hotmail.com.
8
University Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, RJ, Brazil. mael.nilo@hotmail.com.
9
Department of Clinical Analyses and Toxicology, School of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro 21941-599, RJ, Brazil. flaviafrattani@pharma.ufrj.br.
10
University Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, RJ, Brazil. robertofonseca@hucff.ufrj.br.
11
Undergraduate Program in Pharmacology, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil. robertofonseca@hucff.ufrj.br.
12
Program of Glycobiology, Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro 21941-590, RJ, Brazil. vpomin@olemiss.edu.
13
University Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, RJ, Brazil. vpomin@olemiss.edu.
14
Department of BioMolecular Sciences, Division of Pharmacognosy, and Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, Oxford, MS 38677-1848, USA. vpomin@olemiss.edu.

Abstract

The anticoagulant and antithrombotic properties of three structurally correlated sea urchin-derived 3-linked sulfated α-glycans and their low molecular-weight derivatives were screened comparatively through various in vitro and in vivo methods. These methods include activated partial thromboplastin time, the inhibitory activity of antithrombin over thrombin and factor Xa, venous antithrombosis, the inhibition of platelet aggregation, the activation of factor XII, and bleeding. While the 2-sulfated fucan from Strongylocentrotus franciscanus was observed to be poorly active in most assays, the 4-sulfated fucan from Lytechinus variegatus, the 2-sulfated galactan from Echinometra lucunter and their derivatives showed multiple effects. All marine compounds showed no capacity to activate factor XII and similar low bleeding tendencies regardless of the dose concentrations used to achieve the highest antithrombotic effect observed. The 2-sulfated galactan showed the best combination of results. Our work improves the background about the structure-function relationship of the marine sulfated glycans in anticoagulation and antithrombosis. Besides confirming the negative effect of the 2-sulfated fucose and the positive effect of the 2-sulfated galactose on anticoagulation in vitro, our results also demonstrate the importance of this set of structural requirements on antithrombosis in vivo, and further support the involvement of high-molecular weight and 4-sulfated fucose in both activities.

KEYWORDS:

anticoagulation; antithrombosis; marine glycan; sulfated fucan; sulfated galactan

PMID:
30200211
PMCID:
PMC6163371
DOI:
10.3390/md16090304
[Indexed for MEDLINE]
Free PMC Article

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