Long Duration of Anticoagulant Activity and Protective Effects of Acharan Sulfate in Vivo
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Authors
Li, Da Wei
Lee, In Sun
Sim, Joon Soo
Toida, Toshihiko
Linhardt, Robert J.
Kim, Yeong Shik
Issue Date
2004-04-26
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
Abstract
Introduction: We previously reported that a new glycosaminoglycan, acharan sulfate (AS) from the African giant snail Achatina fulica showed anticoagulant activity in vitro, but was much less active when compared to heparin. In the present study, the anticoagulant activity of AS was investigated in vivo. Methods: AS and heparin were administered to mice and rats in various doses and the anticoagulant activities were measured by aPTT assay. Both were also compared in a thrombin-induced lethality animal model. As one of the possible mechanisms, AS-thrombin interaction was studied by using surface plasmon resonance spectroscopy. Results: Intravenous administration of AS to mice prolonged the clotting time (aPTT) in a time and dose-dependent manner. Although the anticoagulant activity was low in rats, it steadily increased over 5 h after administration of AS (30 mg/kg). In contrast, the increase in aPTT induced by 5 mg/kg of heparin was restored to a normal level after 3 h. In a thrombin-induced lethality model in mice, AS (20 mg/kg) protected against lethality by 80%, while heparin (20 mg/kg) did not show any protective activity beyond 3.5 h post-administration. AS could be also detected in plasma even 5 h after i.v. administration to rats. The binding constant (K(D)) of AS to thrombin was 7.27 x 10(-6) M, corresponding to moderate binding affinity. Conclusions: These results show that the longer duration of AS in blood could prolong the clotting time determined by aPTT and offering protection against thrombin-induced lethality. One possible mechanism may result from AS-thrombin interaction.
Description
Thrombosis Research, 113,67-73
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Full Citation
Long Duration of Anticoagulant Activity and Protective Effects of Acharan Sulfate in Vivo, D.-W. Li, I. S. Lee, J.-S. Sim, T. Toida, R. J. Linhardt, Y. S. Kim, Thrombosis Research, 113,67-73, 2004.
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PubMed ID
DOI
ISSN
493848