Anticoagulant and antithrombotic activities of a chemically sulfated galactoglucomannan obtained from the lichen Cladonia ibitipocae.
A galactoglucomannan (GGM), isolated from the lichen Cladonia ibitipocae, consisted of a (1-->6)-linked main chain of alpha-mannopyranose units, substituted by alpha- and beta-D-galacto (alpha- and beta-D-Galp)-, beta-D-gluco (beta-D-Glcp)- and alpha-D-mannopyranosyl (alpha-D-Manp) groups, and was sulfated giving a sulfated polysaccharide (GGM-SO4) with 42.2% sulfate corresponding to a degree of substitution of 1.29. NMR studies indicated that after sulfation, the OH-6 groups of galactopyranosyl and mannopyranosyl units were preferentially substituted. GGM-SO4 was investigated in terms of its in vitro anticoagulant and in vivo antithrombotic properties. Those of the former were evaluated by its activated partial thromboplastin (APTT) and thrombin time (TT), using pooled normal human plasma, and compared with that of 140 USP units mg(-1) for a porcine intestinal mucosa heparin. Anticoagulant activity was detected in GGM-SO4, but not in GGM. The in vivo antithrombotic properties of GGM-SO4 were evaluated using a stasis thrombosis model in Wistar rats, intravenous administration of 2 mg kg(-1) body weight totally inhibiting thrombus formation. It caused dose-dependent increases in tail transection bleeding time. The results obtained showed that this sulfated polysaccharides is a promising anticoagulant and antithrombotic agent.
Martinichen-Herrero
J C
JC
Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, C.P. 19046, 81531-990 Curitiba-PR, Brazil.
Carbonero
E R
ER
Sassaki
G L
GL
Gorin
P A J
PA
Iacomini
M
M
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001760:Bleeding Time; D001777:Blood Coagulation; D001835:Body Weight; D004305:Dose-Response Relationship, Drug; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D008401:Gas Chromatography-Mass Spectrometry; D006493:Heparin / Q000737:chemistry; D007413:Intestinal Mucosa / Q000378:metabolism; D008011:Lichens / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008351:Mannans / Q000737:chemistry*; D008358:Mannose / Q000737:chemistry; D008745:Methylation; D010314:Partial Thromboplastin Time; D011134:Polysaccharides / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D013552:Swine; D013918:Thrombin Time; D020246:Venous Thrombosis / Q000188:drug therapy* / Q000473:pathology
D000925:Anticoagulants; D005343:Fibrinolytic Agents; D008351:Mannans; D011134:Polysaccharides; C443804:galactoglucomannan; D006493:Heparin; D008358:Mannose