Long Duration of Anticoagulant Activity and Protective Effects of Acharan Sulfate in Vivo

Authors
Li, Da Wei
Lee, In Sun
Sim, Joon Soo
Toida, Toshihiko
Linhardt, Robert J.
Kim, Yeong Shik
ORCID
https://orcid.org/0000-0003-2219-5833
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Other Contributors
Issue Date
2004-04-26
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Degree
Terms of Use
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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.
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
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Department
The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
Publisher
Relationships
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
Thrombosis Research
https://harc.rpi.edu/
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https://login.libproxy.rpi.edu/login?url=https://doi.org/10.1016/j.thromres.2004.02.003