HISTAMINE-RELEASE BY FREE-RADICALS - EFFECT OF DEFIBROTIDE (DFT) AND ITS FRACTION PO-085-DV

The effects of defibrotide (DFT) and its fraction P.O. 085 D V on rat serosal mast cell histamine release evoked by free radicals were studi ed. Free radical production was obtained with: a) metabolic activation of arachidonic acid and cocaine by means of liver microsomes (S-10 mi x) from polychlorinated biphenyl mixture (PCB)-treated rats; b) metabo lic activation of arachidonic acid by means of prostaglandin-H-synthet ase (PHS) and c) human platelet aggregation induced by arachidonic aci d. DFT and its fraction reduced histamine release evoked by aggregatin g human platelets; P.O. 085 D V significantly reduced histamine releas e evoked by metabolic activation of both cocaine and arachidonic acid in the presence of S-10 mix, while DFT was less active on the cocaine- S 10 mix system and ineffective on the arachidonic acid-S 10 mix syste m. Both drugs were unable to decrease histamine release induced by met abolic activation of arachidonic acid in the presence of PHS.