Ferulic acid ethyl ester (FAEE) is an
ester derivative of
ferulic acid, the latter known for its anti-inflammatory and
antioxidant properties. Previous studies from our laboratory have shown that
ferulic acid protects synaptosomal membrane system and neuronal cell culture systems against
hydroxyl and
peroxyl radical oxidation. FAEE is lipophilic and is able to penetrate
lipid bilayer. Previous studies reported that FAEE reduces Alzheimer's
amyloid beta peptide Abeta(1-42)-induced oxidative stress and cytotoxicity in neuronal cell culture by direct radical scavenging and by inducing certain
antioxidant proteins. In the present study we tested the hypothesis that FAEE would provide neuroprotection against
free radical oxidative stress in vivo. Synaptosomes were isolated from the gerbils that were previously injected intraperitoneally (i.p.) with FAEE or
DMSO and were treated with
oxidants, Fe(2+)/H(2)O(2) or 2,2-azobis(2-amidino-propane)dihydrochloride (
AAPH). Synaptosomes isolated from the gerbil previously injected i.p. with FAEE and treated with Fe(2+)/H(2)O(2) and
AAPH showed significant reduction in
reactive oxygen species (ROS), levels of
protein carbonyl,
protein bound
4-hydroxynonenal (HNE, a lipid peroxidation product), and
3-nitrotyrosine (3-NT, another marker of
protein oxidation formed by reaction of
tyrosine residues with
peroxynitrite) compared to Fe(2+)/H(2)O(2) or
AAPH induced oxidative stress in synapotosomes isolated from the brain of gerbils that were previously injected with
DMSO. The synaptosomes isolated from gerbil pre-injected with FAEE and subsequently treated with
AAPH or Fe(2+)/H(2)O(2) showed induction of
heme oxygenase (HO-1) and
heat shock protein 70 (HSP-70) but reduced
inducible nitric oxide synthase (iNOS) levels. These results are discussed with reference to potential use of this lipophilic
antioxidant phenolic compound in the treatment of oxidative stress-related
neurodegenerative disorders.