Inhibition of arachidonic acid-induced vasogenic brain edema by the non-glucocorticoid 21-aminosteroid U74006F.

The effects of the novel non-glucocorticoid 21-aminosteroid U74006F on arachidonic acid (AA)-induced vasogenic brain edema were examined in rats. Vasogenic edema was assessed in terms of the extent of Evan's blue extravasation after subcortical micro-injection of AA indicative of blood-brain barrier disruption. U74006F, given i.v. at 15 min before the AA, produced a dose-related reduction in the area of subsequent Evan's blue staining measured in a coronal brain cross-section through the injection site. The highest dose tested (1.0 mg/kg) resulted in a 65% decrease in the area of blood-brain barrier disruption in comparison to that seen in vehicle-treated animals (P less than 0.0001). The mechanism of the anti-edema effect of U74006F is discussed in relation to the previously demonstrated ability of the compound to inhibit oxygen free radical-mediated lipid peroxidation.