Effect of YM737, a new glutathione analogue, on ischemic brain edema.

We investigated the effect of YM737, a monoester of glutathione (GSH), on brain edema and GSH content after occlusion of a middle cerebral artery (MCA) in the rat. The drug possesses stronger radical scavenging activity than GSH itself, and is more effectively transported into cells. Hemispheric water, sodium, and potassium contents were determined at 2.5 and 24 hours after MCA occlusion. The animals received either YM737 or GSH immediately after occlusion. Cerebral GSH content was measured by HPLC after 2.5 hours of ischemia. The increases in water and sodium contents at 2.5 and 24 hours after MCA occlusion were significantly suppressed by YM737. GSH content decreased by 53% in the caudate, and by 22% in the cortex after ischemia. YM737 significantly ameliorated the GSH decrease in the caudate, while administration of GSH showed little effects on the ischemia-induced changes in water, sodium, and GSH contents. The result suggests the role of free radicals in the pathogenesis of ischemic brain edema.