Abstract
β-D xylosides have been shown to have venous antithrombotic properties after simple
oral administration. Therefore, the arterial antithrombotic effect of these compounds
was investigated in vivo, using the experimental thrombosis model induced by laser injury. The products tested
were administered orally, 4 h before the thrombosis induction. Two β-D xylosides were
tested (LF 09-0055 and LP 05-0030), either after a simple oral administration at 50,
100, 200, and 400 mg/kg, or after repetitive oral administration at 200 mg/kg twice
daily during 5 days. These compounds increased significantly the number of laser shots
required to induce arterial thrombosis and decreased the number of emboli and the
duration of embolization. At single-dose or repeated administrations, these xylosides
did not affect diluted thrombin time in platelet-poor plasma collected after thrombosis
inductions. They induced a dermatan sulfatelike activity in the plasma of treated
rats, as measured by heparin cofactor II-mediated thrombin inhibition assay. These
data suggest that these xylosides are potent arterial antithrombotic agents after
single or repetitive oral administrations. β-D xylosides constitute a very promising
therapeutic class of orally active antithrombotic drugs.
Keywords:
β-D xylosides - arterial thrombosis - glycosaminoglycan - dermatan sulfate-like activity
- laser
