INHIBITION OF THE THROMBOPENIC EFFECT OF ELLAGIC ACID BY PCR 4099, AN ANTIAGGRGATING AGENT, IN RATS.

In the rat, intravenous injection of large doses (30 mg/Kg) of ellagic acid (EA) induced a decrease in the plasma level of fibrinogen and in the blood platelet content and an increase of the activated partial thromboplastin time. EA induced the accumulation of Crs1-labelled platelets into the lung and the liver accompanied by a 64% fall in Cr51 blood radioactivity.

The long-lasting thrombocytopenia induced by EA was inhibited by heparin (4 mg/Kg), defibrase (20 U/Kg), and clocoumarol (4 mg/Kg). It was not inhibited by aspirin (90 mg/Kg), indomethacin (8 mg/Kg) and ketoprofen (4-10 mg/Kg). The thrombocytopenia would depend on an intravascular coagulation.

Using this model of platelet stimulation, we studied the protective effect of PCR 4099. This drug was first given as a single dose, orally four hours before the injection of EA. It reduced the thrombocytopenia for 10 mg/Kg and suppressed it for 40 mg/Kg. The thrombocytopenia was also inhibited by 3 day oral administration of PCR 4099 4 mg/Kg. PCR 4099 is thus a potent inhibitor of this kind of platelet stimulation.