Ebselen (DR3305) ameliorates delayed cerebral vasospasm in a canine two-hemorrhage model

Abstract

Ebselen, a seleno-organic compound which inhibits arachidonic acid lipoxygenase activity and exerts glutathione peroxidase-like activity, ameliorated delayed cerebral vasospasm in a canine two-hemorrhage model. Twenty-five dogs were exposed to subarachnoid hemorrhage and divided into two groups. In the Ebselen-treated group (6 dogs), 50 mg kg-1 of Ebselen was administered twice a day, for 7 days. The other 19 dogs without administration of Ebselen were used as a control group. In the Ebselen-treated group, the basilar artery on Day 7 after subarachnoid hemorrhage was constricted to 68.1 +/- 6.4% (mean +/- SD, n = 6) of the angiographic diameter on Day 0, before subarachnoid hemorrhage. This percentage was significantly larger than the 41.3 +/- 4.6% (n = 19) in the control group. The basilar artery segment obtained on Day 7 in the Ebselen-treated group produced 3.32 +/- 1.82 nmol of 5-hydroxyeicosatetraenoic acid/mg protein/5 minutes (n = 5), significantly less than the 6.73 +/- 0.95 (n = 3) produced by the artery in the control group. Thus, administration of Ebselen suppressed arachidonate 5-lipoxygenase activation and had a beneficial effect on angiographically detected delayed vasospasm.