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

• Published in: Marine drugs Vol. 16; no. 9; p. 304
• Main Authors: Vasconcelos, Ariana A, Sucupira, Isabela D, Guedes, Alessandra L, Queiroz, Ismael N, Frattani, Flavia S, Fonseca, Roberto J, Pomin, Vitor H
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 30.08.2018; MDPI AG
• Subjects: Adult; Animals; Anticoagulants - chemistry; Anticoagulants - isolation & purification; Anticoagulants - pharmacology; Anticoagulants - therapeutic use; anticoagulation; antithrombosis; Disease Models, Animal; Drug Evaluation, Preclinical; Factor Xa - metabolism; Factor XII - metabolism; Female; Fibrinolytic Agents - chemistry; Fibrinolytic Agents - isolation & purification; Fibrinolytic Agents - pharmacology; Fibrinolytic Agents - therapeutic use; Healthy Volunteers; Humans; Male; marine glycan; Molecular Structure; Molecular Weight; Partial Thromboplastin Time; Polysaccharides - chemistry; Polysaccharides - isolation & purification; Polysaccharides - pharmacology; Polysaccharides - therapeutic use; Rabbits; Rats; Rats, Wistar; Sea Urchins - chemistry; Structure-Activity Relationship; sulfated fucan; sulfated galactan; Sulfates - chemistry; Thromboplastin - administration & dosage; Venous Thrombosis - chemically induced; Venous Thrombosis - drug therapy; Young Adult; sulfated fucan; marine glycan; sulfated galactan; anticoagulation; antithrombosis
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md16090304

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 was observed to be poorly active in most assays, the 4-sulfated fucan from , the 2-sulfated galactan from 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.