PAF-induced thrombocytopenia

PAF-induced oxidative burst in human PMNL. In guinea pigs, yangambin inhibited PAF-induced thrombocytopenia but did not affect leukocytopenia. 

The antagonistic properties of FR 900452 have also been examined in a model of endotoxin shock, the haemodynamic and haematological manifestations of this condition closely resembling the changes induced by PAF. FR 900452 (10 mg/kg, i.v.) almost completely prevents PAF (1 /ig/kg, i.v.)-induced thrombocytopenia and leukocytopenia in rabbits [295]. It also significantly inhibits endotoxin (E. coli LPS, 30 /ig/kg, i.v.)-induced thrombocytopenia but not leukocytopenia. The same dose of FR 900452 also causes the decreased arterial blood pressure to return to normal in the endotoxin-induced rat hypotension model, an effect also reported for other PAF inhibitors [121, 274], Finally, FR 900452 has been tested for its therapeutic effect on rat nephrosis induced by aminonucleoside (puromycin, 100 mg/kg, i.p.). At 100 mg/kg twice a day orally for 6 days, the agent significantly reduces urinary protein loss in nephrotic rats [298]. 

Guinea pigs, hamsters, or mice are anesthetized with pentobarbital sodium (i.p.) and Rompun (i.m.) and placed on an electrically warmed table at 37 °C. The carotid artery is cannulated for blood withdrawal and the jugular vein is cannulated to administer the thrombocytopenia-inducing substances collagen + adrenaline (injection of the mixture of both within 10 s) or PAF or thrombin. In mice collagen + adrenaline are injected into a tail vein. 

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