The anti-inflammatory effects of
pranlukast, an antagonist of
cysteinyl leukotriene receptor 1, may be rendered not only by antileukotriene activity but also by other pharmacological activities. Previous studies indicate that
pranlukast reduces ischemic tissue injury partially through decreasing vascular permeability, but its effect on ischemic injury in endothelial cells is not known. Thus, in this study, we investigated the effect of
pranlukast on
ischemia-like injury induced by
oxygen-
glucose deprivation (OGD) in EA.hy926 cells, a human endothelial cell line, and the possible mechanisms. We found that cell viability was reduced,
lactate dehydrogenase release was increased 4-8 hours after OGD, and
necrosis was induced 8 hours after OGD. Production of
reactive oxygen species (ROS) increased by 211%, 176%, and 128%, respectively, 0.5, 1, and 2 hours after OGD.
Nuclear factor-kappaB (
NF-kappaB) was translocated to the nuclei 4-8 hours after OGD.
Pranlukast ameliorated the reduced viability, the increased
lactate dehydrogenase release, and
necrosis after OGD. It also reduced ROS production and inhibited
NF-kappaB nuclear translocation after OGD. The ROS scavenger,
edaravone, inhibited OGD-induced nuclear translocation of
NF-kappaB as well.
Edaravone and
pyrrolidine dithiocarbamate (a specific
NF-kappaB inhibitor) protected endothelial cells from the OGD-induced injury. However,
zileuton, a
5-lipoxygenase inhibitor, did not affect the cell injury, ROS production, and
NF-kappaB nuclear translocation after OGD. The exogenous
leukotriene D4 did not induce cell injury, ROS production, and
NF-kappaB translocation. Thus, we conclude that
pranlukast protects endothelial cells from
ischemia-like injury via decreasing ROS production and inhibiting
NF-kappaB activation, which is
leukotriene independent.