Slight differences in sulfation of algal galactans account for differences in their anticoagulant and venous antithrombotic activities.
We compared sulfated galactans (SGs) from two species of red algae using specific coagulation assays and experimental models of thrombosis. These polysaccharides have an identical saccharide structure and the same size chain, but with slight differences in their sulfation patterns. As a consequence of these differences, the two SGs differ in their anticoagulant and venous antithrombotic activities. SG from G. crinale exhibits procoagulant and prothrombotic effects in low doses (up to 1.0 mg/kg body weight), but in high doses (>1.0 mg/kg) this polysaccharide inhibits both venous and arterial thrombosis in rats and prolongs ex-vivo recalcification time. In contrast, SG from B. occidentalis is a very potent anticoagulant and antithrombotic compound in low doses (up to 0.5 mg/kg body weight), inhibiting venous experimental thrombosis and prolonging ex-vivo recalcification time, but these effects are reverted in high doses. Only at high doses (>1.0 mg/kg) the SG from B. occidentalis inhibits arterial thrombosis. As with heparin, SG from G. crinale does not activate factor XII, while the polysaccharide from B. occidentalis activates factor XII in high concentrations, which could account for its procoagulant effect at high doses on rats. Both SGs do not modify bleeding time in rats. These results indicate that slight differences in the proportions and/or distribution of sulfated residues along the galactan chain may be critical for the interaction between proteases, inhibitors and activators of the coagulation system, resulting in a distinct pattern in anti- and procoagulant activities and in the antithrombotic action.
Fonseca
Roberto J C
RJ
Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Programa de Glicobiologia, Instituto de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Brazil.
Oliveira
Stephan-Nicollas M C G
SN
Melo
Fábio R
FR
Pereira
Maria G
MG
Benevides
Norma M B
NM
Mourão
Paulo A S
PA
D000818:Animals; D000925:Anticoagulants / Q000009:adverse effects / Q000302:isolation & purification / Q000494:pharmacology*; D001760:Bleeding Time; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015956:Factor XIIa / Q000378:metabolism; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000302:isolation & purification / Q000494:pharmacology*; D005685:Galactans / Q000009:adverse effects / Q000302:isolation & purification / Q000494:pharmacology*; D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D008297:Male; D015394:Molecular Structure; D008970:Molecular Weight; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D000461:Rhodophyta / Q000737:chemistry*; D013431:Sulfates / Q000009:adverse effects / Q000302:isolation & purification / Q000494:pharmacology*; D013927:Thrombosis / Q000097:blood / Q000517:prevention & control*; D020246:Venous Thrombosis / Q000097:blood / Q000517:prevention & control
D000925:Anticoagulants; D005343:Fibrinolytic Agents; D005685:Galactans; D013431:Sulfates; D006493:Heparin; D015956:Factor XIIa