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Anticoagulant and Antithrombotic Properties of Three Structurally Correlated Sea Urchin Sulfated Glycans and Their Low-Molecular-Weight Derivatives.
- Source :
-
Marine drugs [Mar Drugs] 2018 Aug 30; Vol. 16 (9). Date of Electronic Publication: 2018 Aug 30. - Publication Year :
- 2018
-
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.
- Subjects :
- Adult
Animals
Anticoagulants chemistry
Anticoagulants isolation & purification
Anticoagulants therapeutic use
Disease Models, Animal
Drug Evaluation, Preclinical
Factor Xa metabolism
Female
Fibrinolytic Agents chemistry
Fibrinolytic Agents isolation & purification
Fibrinolytic Agents therapeutic use
Healthy Volunteers
Humans
Male
Molecular Structure
Molecular Weight
Partial Thromboplastin Time
Polysaccharides chemistry
Polysaccharides isolation & purification
Polysaccharides therapeutic use
Rabbits
Rats
Rats, Wistar
Structure-Activity Relationship
Sulfates chemistry
Thromboplastin administration & dosage
Venous Thrombosis chemically induced
Young Adult
Anticoagulants pharmacology
Factor XII metabolism
Fibrinolytic Agents pharmacology
Polysaccharides pharmacology
Sea Urchins chemistry
Venous Thrombosis drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1660-3397
- Volume :
- 16
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Marine drugs
- Publication Type :
- Academic Journal
- Accession number :
- 30200211
- Full Text :
- https://doi.org/10.3390/md16090304