Relationship between antithrombotic activities of fucans and their structure

被引:44
作者
Boisson-Vidal, C
Chaubet, F
Chevolot, L
Sinquin, C
Theveniaux, J
Millet, J
Sternberg, C
Mulloy, B
Fischer, AM
机构
[1] Natl Inst Biol Stand & Controls, Mol Struct Lab, Potters Bar EN6 3QG, Herts, England
[2] Hop Necker Enfants Malad, Lab Rech Hemostase, Paris, France
[3] Lab Fournier, Dijon, France
[4] IFREMER, Lab Biochim & Mol Marines, Unite Rech Marine 2, Nantes, France
[5] IFREMER, Lab Rech Macromol, CNRS, UMR 7540,Unite Rech Marine 2, Villetaneuse, France
关键词
low molecular weight fucan; thrombosis; anticoagulant activity; antithrombotic action; structure/antithrombotic activity relationships;
D O I
10.1002/ddr.2
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
A low molecular weight fucan fraction extracted from the brown seaweed Ascophyllum nodosum was previously shown to exhibit dose-related venous antithrombotic activity with an ED80 of about 20 mg/kg, 2 h after a single subcutaneous injection HCII (Colliec et al. [1991] Thromb Res 64:143-154; Mauray et al. [1995] Thromb Haemast 74:1280-1285). Its activity was comparable to that of a low molecular weight heparin (Dalteparin(R)). This fucan fraction is one of several, with a range of different structure parameters, prepared by degradation of the whole native fucan. These low molecular weight fractions were compared using a Wessler stasis thrombosis model in rabbits and by determination of their in vitro and ex vivo anticoagulant activities. Intravenous administrations of these fractions reduced thrombosis in a dose-dependent manner. Partial removal of sulfate groups and/or partial degradation lead to a significant decrease in their anticoagulant and antithrombotic activities. The integrity of the regular pattern of sulphation of the fucoidan is necessary for antithrombotic activity. (C) 2001 Wiley-Liss. Inc.
引用
收藏
页码:216 / 224
页数:9
相关论文
共 30 条
[1]  
BOISSON-VIDAL C, 1991, Drugs of the Future, V16, P539
[2]  
Chaubet F, 2000, PR PHYT SOC, V44, P59
[3]   Further data on the structure of brown seaweed fucans: relationships with anticoagulant activity [J].
Chevolot, L ;
Foucault, A ;
Chaubet, F ;
Kervarec, N ;
Sinquin, C ;
Fisher, AM ;
Boisson-Vidal, C .
CARBOHYDRATE RESEARCH, 1999, 319 (1-4) :154-165
[4]   A study of fucoidan from the brown seaweed Chorda filum [J].
Chizhov, AO ;
Dell, A ;
Morris, HR ;
Haslam, SM ;
McDowell, RA ;
Shashkov, AS ;
Nifant'ev, NE ;
Khatuntseva, EA ;
Usov, AI .
CARBOHYDRATE RESEARCH, 1999, 320 (1-2) :108-119
[5]  
CHURCH FC, 1989, J BIOL CHEM, V264, P3618
[6]   A LOW-MOLECULAR-WEIGHT FUCOIDAN FRACTION FROM THE BROWN SEAWEED PELVETIA-CANALICULATA [J].
COLLIEC, S ;
BOISSONVIDAL, C ;
JOZEFONVICZ, J .
PHYTOCHEMISTRY, 1994, 35 (03) :697-700
[7]   ANTICOAGULANT PROPERTIES OF A FUCOIDAN FRACTION [J].
COLLIEC, S ;
FISCHER, AM ;
TAPONBRETAUDIERE, J ;
BOISSON, C ;
DURAND, P ;
JOZEFONVICZ, J .
THROMBOSIS RESEARCH, 1991, 64 (02) :143-154
[8]   Mechanism of heparin activation of antithrombin -: Role of individual residues of the pentasaccharide activating sequence in the recognition of native and activated states of antithrombin [J].
Desai, UR ;
Petitou, M ;
Björk, I ;
Olson, ST .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (13) :7478-7487
[9]  
DISCHE Z, 1955, Methods Biochem Anal, V2, P313, DOI 10.1002/9780470110188.ch11
[10]  
FAREED J, 1995, EXPERT OPIN INV DRUG, V4, P389