350 rub
Journal №12 for 2012 г.
Article in number:
The influence of anticoagulant activity of sulfated cellulose, obtained from Pópulus trémula wood, on mobility of their precipitates with protamine sulfate in the electric field
Keywords: sulfated cellulose sulfation degree molecular weight anticoagulant mediated antithrombin activity mediated anti-factor Xa activity precipitation with prothamine sulfate
Authors:
E.Y. Savchik, N.N. Drozd, S.A. Kuznetsova, V.A. Makarov, A.V. Levdanskiy
Abstract:
Sulfated polysaccharides (SP) are perspective compounds for elaboration of new anticoagulants based on it, more accessible, economic profitable and possessing lesser hemorrhage effect than heparins. The aim of this work is studying of anticoagulant activity (AA) of sulfated cellulose (SC), obtained from Pópulus trémula wood. Materials and methods: The 6 samples of SC with different molecular weights (MM, 12-19 kDa) and sulfur contents (S, 8,0 - 8,7 %) were studied on AA activity in vitro in standard coagulation and amidolytic assays (were done in citrated plasma) and relationship of AA activity to the mobility of polysaccharides complexes with polycation protamine sulfate (PPS) in the electric field. International unfractionated heparin (UFH) NIBSC standard with antithrombin activity (aIIa) 203 U/mg and anti-factor Xa (aXa) activity 220 U/mg was used as comparison sample. Results and discussion: In standard coagulation assays the clotting time was prolonged by increasing concentrations of studied SP samples. These polysaccharides inhibited amidolytic activity of thrombin without antithrombin (AT) and with AT but in lower concentrations. At the same time, like UFH, they didn-t decrease amidolytic activity of factor Xa without AT. Under addition of AT to the samples amidolytic activity of factor Xa was decreased but worse than under addition of AT to UFH (in 4,8-41 times). The SР samples had nearly identical antithrombotic (45,6±1,0 - 53,8±6,8 U/mg) and anti-factor Xa (8,6±1,8-10,5±2,0 U/mg) activities, except the one with MM 14 kDa and S 8,1%. This polysaccharide had the lowest AA activity (аIIа=12,5 ±1,5 Е/мг, аХа=2,1±0,2 U/mg). Reliable relationship aIIa or aXa with MM or S wasn-t detected. The precipitation peaks - sizes (height and square) greatly positively correlated with аIIа и аХа activities of the SP. The values of аIIа and аХа reasonably positively correlated with the polysaccharides - MM and S. Conclusion: Thus, sulfated cellulose, obtained from Pópulus trémula wood with MM from 12,7 to 18,9 kDa and sulfur content 8,0-8,7 %, are anticoagulants of direct action, those indirect inhibitor activity regarding to thrombin is 5 times higher average than regarding to factor. It is necessary to increase MM>18,9 kDa and sulfur content >8,7 % for receiving more active SC. The mobility of SP - precipitates with PPS in the electric field can be used for primary analysis of their AA activity.
Pages: 46-54
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