Comparative Study on the In Vitro and In Vivo Activities of Heparinoids Derivative Investigated on the Animal Model

Abstract

In this study we compared the antithrombotic and anticoagulant properties of sodium and calcium derivatives of pentosan polysulfate (Na-PPS, Ca-PPS), unfractionated heparin (UFH), and low-molecular-weight heparin (Fraxiparin). The antithrombotic effects of these agents have been investigated in an experimental thrombosis model in which rat mesenteric venules with a diameter of 20-30 microm were injured by well-defined argon laser lesions. Furthermore, the in vivo and in vitro anticoagulant activities [activated partial thromboplastin time (aPTT), Heptest] of these agents have been studied. Thrombus formation was significantly inhibited after s.c. injection of Na-PPS and Ca-PPS in doses >10 mg/kg. The duration of the antithrombotic effect lasted 8 h for Na-PPS and 12 h for Ca-PPS. After oral administration of Na-PPS, an antithrombotic effect was not observed. Oral application of Ca-PPS in doses >20 mg/kg significantly inhibited thrombus formation. Na-PPS and Ca-PPS markedly prolonged clotting time in aPTT and Heptest in concentrations ranging from 0.01 to 0.2 mg/ml rat PTT. Two h after s.c. administration of these agents in a dose of 10 mg/kg, the aPTT increased threefold and the Heptest 2.5-fold compared with controls. After oral application of 50 mg/kg Na-PPS and Ca-PPS, no effect on the coagulation test could be measured. Intravenous injection of UFH prolonged the Heptest after 1 min and the aPTT after 30 min. In ex vivo studies of aPTT and Heptest performed in rat plasma between 2 and 24 h after s.c. injection of 0.2 mg/kg Fraxiparin, no inhibition of any coagulation test was measured. The antithrombotic effect of 0.2 mg/kg Fraxiparin after s.c. injection was significant. Intravenous injection of 20 U/kg UFH significantly inhibited thrombus formation. The smallest antithrombotic effect was after i.v. injection of UFH.

Improved coagulation in bleeding disorders by Non-Anticoagulant Sulfated Polysaccharides (NASP)

“…Fucoidan is polymeric sulfated L-fucose whichisoften isolatedfrom plant tissue and has been associatedw ith anti-inflammatory, anti-proliferative, and antiviral activities (17,39). While both PPSand fucoidan maye xhibit anticoagulant activity,likelyasaresultofheparin cofactor II interaction (40,41), PPSadministeredsubcutaneouslytorats requires doses>5mg/kg to prolong clotting (41) and fucoidan seems well-tolerated in rabbits even when givenintravenouslyat 10 mg/kg (42).Hence, the currentresults supporting improved hemostasis at doses <0.1 mg/kg in hemophilic rodents represent anovel biological property for certain sulfated polysaccharides whichoccursatdose levels in vivo lowerthan other reported effects (17,26,39,42,43).…”

Exogenous glycosaminoglycans coat damaged bladder surfaces in experimentally damaged mouse bladder

“…Both heparin and pentosanpolysulphate have pharmacologic effects on the coagulation system [22], whereas chondroitin sulphate, a normal constituent of the bladder surface, and hyaluronate do not [23]. All of these glycosaminoglycan molecules have effects on mast cells and other cells within the bladder at high concentrations in vitro [24-26].…”

Characterization, chemical modifications and in vitro anticoagulant properties of an exopolysaccharide produced by Alteromonas infernus

“…san polysulfate [13]. This R-(40% sulfate) LMW EPS inhibited thrombin generation after stimulation by both contact-activated and thromboplastin-activated systems (50% inhibition in both systems with the same concentration).…”