title: In vivo protection of synaptosomes by ferulic acid ethyl ester (FAEE) from oxidative stress mediated by 2,2-azobis(2-amidino-propane)dihydrochloride (AAPH) or Fe(2+)/H(2)O(2): insight into mechanisms of neuroprotection and relevance to oxidative stress-related neurodegenerative disorders.
abstract: 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.
authors.affiliation: Department of Chemistry, University of Kentucky, Lexington, KY 40506, USA.
authors.forename: Gururaj
authors.initials: G
authors.lastname: Joshi
authors.forename: Marzia
authors.initials: M
authors.lastname: Perluigi
authors.forename: Rukhsana
authors.initials: R
authors.lastname: Sultana
authors.forename: Ravagna
authors.initials: R
authors.lastname: Agrippino
authors.forename: Vittorio
authors.initials: V
authors.lastname: Calabrese
authors.forename: D Allan
authors.initials: DA
authors.lastname: Butterfield
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000578:Amidines / Q000494:pharmacology*; D000818:Animals; D002109:Caffeic Acids / Q000494:pharmacology*; D005296:Ferrous Compounds / Q000494:pharmacology*; D005849:Gerbillinae; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008297:Male; D019636:Neurodegenerative Diseases / Q000209:etiology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009566:Nitrates / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism
chemical_list: D000447:Aldehydes; D000578:Amidines; D002109:Caffeic Acids; D005296:Ferrous Compounds; D018840:HSP70 Heat-Shock Proteins; D018696:Neuroprotective Agents; D009566:Nitrates; D017382:Reactive Oxygen Species; C099085:ethyl ferulate; C046728:2,2'-azobis(2-amidinopropane); D006861:Hydrogen Peroxide; D052247:Nitric Oxide Synthase Type II; D006419:Heme Oxygenase (Decyclizing); C027576:4-hydroxy-2-nonenal