Ebselen (DR3305) ameliorates delayed cerebral vasospasm in a canine two-hemorrhage model.
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.
Watanabe
T
T
Division of Neurosurgery, Faculty of Medicine, Tottori University, Yonago, Japan.
Nishiyama
M
M
Hori
T
T
Asano
T
T
Shimizu
T
T
Masayasu
H
H
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D001393:Azoles / Q000494:pharmacology*; D001488:Basilar Artery / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D004285:Dogs; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000209:etiology* / Q000503:physiopathology*; D054833:Isoindoles; D016566:Organoselenium Compounds / Q000494:pharmacology*; D013345:Subarachnoid Hemorrhage / Q000150:complications*; D013997:Time Factors; D014661:Vasoconstriction
D001393:Azoles; D006893:Hydroxyeicosatetraenoic Acids; D054833:Isoindoles; D016566:Organoselenium Compounds; C042986:ebselen; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D001094:Arachidonate 5-Lipoxygenase