Preventive effect of MCI-186 on 15-HPETE induced vascular endothelial cell injury in vitro

Abstract

Using cultured bovine aortic endothelial cells, the effects of MCI-186, a radical scavenger, were studied on arachidonic acid metabolism and on the cell injury caused by 15-HPETE. MCI-186 at 3 × 10 −5M enhanced prostacyclin production in the intact endothelial cells without affecting phospholipase A 2. When endothelial cell homogenates were used as an enzyme source, it was found that MCI-186 stimulated the conversion of arachidonic acid to prostacyclin like phenol, perhaps by trapping OH radicals produced in the process of the conversion of PGG 2 to PGH 2. On the other hand, MCI-186 was found to inhibit lipoxygenase metabolism of arachidonic acid in cell free homogenates of rat basophilic leukemia cells. The lipoxygenase inhibition caused by 3 × 10 −5M MCI-186 was almost equivalent to that caused by 3 × 10 −6M BW 755C. MCI-186 remarkably protected against endothelial cell damage caused by 15-HPETE. 3 × 10 −5M of 15-HPETE caused endothelial cell death in about 60% of the population: however, pretreatment of the cells with 10 −5M of MCI-186 or concomitant addition of 10 −5M of MCI-186 with 15-HPETE to the cultures prevented the cell death completely. These results suggest that MCI-186 may become an unique anti-ischemic drug.