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Thromb Haemost ; 86(6): 1540-6, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11776325

RESUMO

Sulfated D-galactans occur on the red algae Botryocladia occidentalis as three fractions that differ in their sulfate content. Fractions F2 and F3 are potent anticoagulants. Like heparin, they enhance thrombin and factor Xa inhibition by antithrombin and/or heparin cofactor II. The inhibition potency increases simultaneously with the sulfate content of the fractions. The antithrombotic activity of these sulfated D-galactans was investigated on an experimental thrombosis model in which thrombus formation was induced by a combination of stasis and hypercoagulability. In contrast with heparin. the sulfated D-galactans showed a dual dose-response curve preventing thrombosis at doses up to approximately 0.5 mg/ kg body weight but losing the effect at higher doses. This unexpected behavior is probably due to a combined action of the sulfated D-galactan as anticoagulant and also as a strong inducer of platelet aggregation. In platelet-depleted animals the antithrombotic activity at higher dose of sulfated D-galactan is restored and almost total inhibition of thrombus formation is achieved. The sulfated D-galactan has no hemorrhagic effect even at high doses, possibly as a consequence of its effect on platelet aggregation. At comparable dose heparin has an intense bleeding effect. These results indicate that new polysaccharides, with well-defined structures, can help to distinguish events, such as antithrombotic and anticoagulant activities, bleeding and platelet-aggregating effects, which are obscure when induced simultaneously by a single compound.


Assuntos
Anticoagulantes/uso terapêutico , Fibrinolíticos/uso terapêutico , Galactanos/uso terapêutico , Fitoterapia , Extratos Vegetais/uso terapêutico , Agregação Plaquetária/efeitos dos fármacos , Rodófitas/química , Trombose Venosa/prevenção & controle , Animais , Anticoagulantes/isolamento & purificação , Anticoagulantes/farmacologia , Anticoagulantes/toxicidade , Brasil , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Feminino , Fibrinolíticos/isolamento & purificação , Fibrinolíticos/farmacologia , Fibrinolíticos/toxicidade , Galactanos/química , Galactanos/isolamento & purificação , Galactanos/farmacologia , Hemorragia/induzido quimicamente , Heparina/farmacologia , Heparina/uso terapêutico , Heparina/toxicidade , Masculino , Tempo de Tromboplastina Parcial , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade , Ratos , Ratos Wistar , Sulfatos/análise , Tromboplastina/toxicidade , Veia Cava Inferior , Trombose Venosa/tratamento farmacológico
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