AbstractCarrageenans are a group of galactan sulphates derived from marine Rhodophyceae. These polymers have been shown to exert a variety of pharmacological effects, several of which involve alterations in both immune and haemostatic responses. Carrageenans were studied for the following reasons:
1. To observe the effects of defined carrageenan fractions on blood coagulation using plasma obtained from polysaccharide treated and untreated rats. Both in vitro and ex vivo samples were then subjected to amidolytic and functional clotting assays. Results obtained suggest that carrageenan is able to inhibit the activity of Factor XII, Factor I and thrombin. Unlike the known activities of the anticoagulant heparin, carrageenan activity was noted in the absence and presence of antithrombin III. The efficacy of carrageenan fractions to exert their particular anticoagulant response may reflect the ability of these polymers through their polyelectrolyte nature to form macromolecular complexes with respect to plasma proteins, thus neutralising their effectiveness in the clotting cascade.
2. Activation of the coagulation pathway also results in the activation of the fibrinotytic response. This activation can take place as a result of Factor II-dependent activation. Results obtained for the fibrinolytic response indicate that carrageenan did inhibit the fibrinolytic pathway when tested in vitro. However, plasma samples obtained from carrageenan treated animals were found to have enhanced fibrinolytic activity.
3. The kallikrein-kinin pathway, like fibrinolysis, may be triggered through Factor XII activation. In vitro results suggest that carrageenan inhibits prekallikrein activation while ex vivo an initial potentiation was observed.
4. In the formation of a haemostatic plug, blood platelets play an essential role. The carrageenan per se in vitro had no direct effect on blood platelets. In the presence of aggregating agents adenosine 5’-diphosphate and thrombin, carrageenan inhibits the platelet aggregation response. Platelet-rich plasma obtained from carrageenan treated rats suggests that the galactan sulphate may induce thrombocytopenia. Platelets from carrageenan treated rats were observed to have a reduced response to adenosine 5’-diphosphate and thrombin-induced platelet aggregation.
5. Carrageenan-lipoprotein effects were investigated to correlate lipoprotein levels with blood coagulation. Results suggest that macroion complex formation between lipoprotein lipase receptors and carrageenan may result in a release of the lipase into the blood stream.
6. Finally, the immunosuppressive effect of carrageenan on the rat model was investigated. Preliminary studies suggest that the polyelectrolyte nature of the carrageenan may influence its role as an immunosuppressive agent.
|Date of Award||Apr 1984|