In vivo protective effects of ferulic acid ethyl ester against amyloid-beta peptide 1-42-induced oxidative stress.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the deposition of amyloid-beta peptide (Abeta), a peptide that as both oligomers and fibrils is believed to play a central role in the development and progress of AD by inducing oxidative stress in brain. Therefore, treatment with antioxidants might, in principle, prevent propagation of tissue damage and neurological dysfunction. The aim of the present study was to investigate the in vivo protective effect of the antioxidant compound ferulic acid ethyl ester (FAEE) against Abeta-induced oxidative damage on isolated synaptosomes. Gerbils were injected intraperitoneally (i.p.) with FAEE or with dimethylsulfoxide, and synaptosomes were isolated from the brain. Synaptosomes isolated from FAEE-injected gerbils and then treated ex vivo with Abeta(1-42) showed a significant decrease in oxidative stress parameters: reactive oxygen species levels, protein oxidation (protein carbonyl and 3-nitrotyrosine levels), and lipid peroxidation (4-hydroxy-2-nonenal levels). Consistent with these results, both FAEE and Abeta(1-42) increased levels of antioxidant defense systems, evidenced by increased levels of heme oxygenase 1 and heat shock protein 72. FAEE led to decreased levels of inducible nitric oxide synthase. These results are discussed with potential therapeutic implications of FAEE, a brain accessible, multifunctional antioxidant compound, for AD involving modulation of free radicals generated by Abeta.
Perluigi
Marzia
M
Department of Biochemical Sciences, University of Rome La Sapienza, Rome, Italy.
Joshi
Gururaj
G
Sultana
Rukhsana
R
Calabrese
Vittorio
V
De Marco
Carlo
C
Coccia
Raffaella
R
Cini
Chiara
C
Butterfield
D Allan
DA
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002109:Caffeic Acids / Q000494:pharmacology*; D005849:Gerbillinae; D050884:HSP72 Heat-Shock Proteins / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects; D009603:Nitroso Compounds / Q000032:analysis; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis / Q000187:drug effects
C443112:3-nitrosotyrosine; D016229:Amyloid beta-Peptides; D000975:Antioxidants; D002109:Caffeic Acids; D050884:HSP72 Heat-Shock Proteins; D018696:Neuroprotective Agents; D009603:Nitroso Compounds; D017382:Reactive Oxygen Species; D014443:Tyrosine; C099085:ethyl ferulate; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1