Nitronyl nitroxides (NN) effectively decompose free radicals (. As brain endothelium,
forming the blood-brain barrier (BBB), is both the main source and the target of reactive
species during cerebral oxidative stress, we studied the effect of NN on brain endothelial
cells injured by the mediator of oxidative stress H(2)O(2) (. H(2)O(2) caused hydroxyl
radical generation, lipid peroxidation, membrane dysfunction, membrane leak and cell
death, concentration dependently. Due to 0.5 mM H(2)O(2), oxy-radical-induced membrane
phospholipid peroxidation (malondialdehyde) increased to 0.61+/-0.04 nmol/mg protein
vs control (0.32+/-0.03, p<0.05), cells lost cytosolic proteins into the medium and
viability decreased to 28+/-2% of control (p<0.05). Permeability through the endothelial
monolayer (measure for the tightness of the BBB) rose to 250+/-40% after 0.15 mM H(2)O(2)
(p<0.001). Addition of 10 microM of the NN 5,5-dimethyl-2,4-diphenyl-4-methoxy-2-imidazoline-3-oxide-1-oxyl
(NN-2), 1 mM phenylbutyl nitrone (PBN), or 10 microM of the lazaroid U83836E improved
cell viability during incubation with 0.5 mM H(2)O(2) to 57+/-1%, 49+/-2%, and 42+/-3%
(p<0.05, vs drug-free H(2)O(2) group). The permeability enhancement by 0.15 mM H(2)O(2)
was reduced to 171+/-21%, 170+/-25%, and 118+/-32% (p<0.05 vs drug-free H(2)O(2) group).
Generally, the assumption is supported that during cerebral oxidative stress the protection
should also be directed to the cells of the BBB, which can be provided by antioxidative
approaches. NN represent a new group of antioxdatively acting cytoprotectiva improving
the survival and function of the endothelium against oxidative stress.