Effects of zileuton, a 5-Lipoxygenase inhibitor, in experimental intracranial hemorrhage

Abstract

The 5-lipoxygenase is a key enzyme involved in the biosynthesis of leukotrienes and its inhibition showed neuroprotective effects in various models of central nervous system diseases such as cerebral ischemia, epilepsy, and Alzheimers disease. In this study, we investigate whether zileuton, administered after intracerebral hemorrhage (ICH), can reduce cerebral edema and hemorrhage volume in a rodent experimental model of ICH. ICH was induced via stereotactic administration of bacterial collagenase in Sprague-Dawley rats. Edema was calculated as the increased amount of water content of the cerebral hemisphere compared to that of the cerebellum, Hemorrhage size was quantified by a spectrophotometric assay. Edema was reduced in the double-dose group compared to the ICH-only group (3.50±0.17% vs. 5.22±0.37%

p=0.008). The administration of zileuton did not show a change in hemorrhage size (p=0.548). These results show zileuton treatment may have neuroprotective effects after ICH through reduction of perihematomal edema.