Algal fucoidan, unlike heparin, has thrombolytic activity in a murine arterial thrombosis model

Thrombolytic effects of fucoidans were investigated in the FeCl3-induced arterial thrombus mouse model and compared with heparin and tissue plasminogen activator (t-PA). Thrombosis model was made by applying 5% FeCl3 on the carotid artery of a Balb/c mouse. Twenty minutes after complete occlusion, a couple of test agents including fucoidan were infused into each mouse group with various doses intravenously, before measuring the time to reperfusion. The occluded arteries were reperfused 37.5 ± 12.4 min after administration of unfractionated fucoidan from Undaria pinnatifida sporophylls (UPS-UF) with a dose of 100 mg/kg. In the mice given either a low-molecular-weight UPS fucoidan or fucoidan source from Fucus vesiculosus (FV-UF), reperfusion was delayed at 55.0 ± 8.0 min with a higher reperfusion effective dose (RED) of 1 g/kg or at 63.3 ± 7.2 at RED of 200 mg/kg, respectively. In the control mice given t-PA of 15 mg/kg, reperfusion occurred at 24.8 ± 6.5 min after administration. In contrast, reperfusion was not observed in the occluded mice given heparin (P < 0.001) in the range of 60-1000 mg/kg. Minimal injection of fucoidan in addition to a given t-PA-enabled restoration of blood flow in the blocked artery without reocclusion at 17.2 ± 2.3 min postinjection (P < 0.002). In conclusion, algal fucoidan has both thrombolytic activity and a stimulatory effect on the thrombolytic activity of t-PA in a dose-dependent manner at an arterial thrombosis model.