title: An antithrombotic fucoidan, unlike heparin, does not prolong bleeding time in a murine arterial thrombosis model: a comparative study of Undaria pinnatifida sporophylls and Fucus vesiculosus.
abstract: The antithrombotic activities and bleeding effects of selected fucoidans (source from either Undaria pinnatifida sporophylls or from Fucus vesiculosus) have been compared with heparin in the ferric chloride-induced arterial thrombus mouse model. Thrombosis was induced by applying 5% ferric chloride for 3 min on the carotid artery region of Balb/c mouse. Five minutes prior to thrombus induction, mice were infused through the tail vein with either saline (control) or polysaccharides. Either fucoidan or heparin was dosed at 0.1, 1.25, 2.5, 5.0, 10, 25, or 50 mg/kg intravenously (i.v.) The carotid blood flow was monitored until more than 60 min post-thrombus induction. Mouse tail transection bleeding time was measured up to 60 min after making a cut in the mouse tail. Both antithrombotic and bleeding effects were observed in a dose-dependent manner for both fucoidans and heparin. Thrombus formation was totally (reflected by Doppler flow meter) inhibited at either 5 or 50 mg/kg of unfractionated Undaria fucoidan or a low-molecular-weight Undaria fucoidan fraction, respectively, without prolonging the time-to-stop bleeding compared with the control (p < 0.01). The total inhibition of thrombus formation was observed for unfractionated Fucus fucoidan at 25 mg/kg where the time-to-stop bleeding was still significantly prolonged, by as much as 8 ± 1.7 min (p < 0.02). In contrast the heparin-treated group showed total inhibition of thrombus formation even at a small dose of 0.8 mg/kg (400 IU) at which bleeding continued until 60 min. In conclusion algal fucoidans are highly antithrombotic without potential haemorrhagic effects compared with heparin in the arterial thrombus model, but this property differs from algal species to species, and from the molecular structure of fucoidans.
authors.affiliation: Department of Biomedical Engineering and Radiology, School of Medicine, Catholic University of Daegu, Daegu, Korea.
authors.forename: Soon-Ki
authors.initials: SK
authors.lastname: Min
authors.forename: Oh-Choon
authors.initials: OC
authors.lastname: Kwon
authors.forename: Sub
authors.initials: S
authors.lastname: Lee
authors.forename: Ki-Hyuk
authors.initials: KH
authors.lastname: Park
authors.forename: Jong-Ki
authors.initials: JK
authors.lastname: Kim
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D001760:Bleeding Time; D002712:Chlorides / Q000494:pharmacology; D004195:Disease Models, Animal; D005290:Ferric Compounds / Q000494:pharmacology; D005343:Fibrinolytic Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D044645:Fucus / Q000737:chemistry*; D006493:Heparin / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011134:Polysaccharides / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D013927:Thrombosis / Q000139:chemically induced / Q000188:drug therapy*; D044648:Undaria / Q000737:chemistry*
chemical_list: D000925:Anticoagulants; D002712:Chlorides; D005290:Ferric Compounds; D005343:Fibrinolytic Agents; D011134:Polysaccharides; D006493:Heparin; C007789:fucoidan; C024555:ferric chloride