title: Protective effects of naringenin on iron-overload-induced cerebral cortex neurotoxicity correlated with oxidative stress.
abstract: Iron is a component of several metalloproteins involved in crucial metabolic processes such as oxygen sensing and transport, energy metabolism, and DNA synthesis. This metal progressively accumulates in the pathogenesis of Alzheimer's (AD) and Parkinson's (PD) diseases. Naringenin (NGEN), a natural flavonoid compound, has been reported to possess neuroprotective effect against PD-related pathology, however, the mechanisms underlying its beneficial effects are poorly defined. Thus, the aim of this study is to investigate the potential mechanism involved in the cytoprotection of NGEN against iron-induced neurotoxicity in the cerebral cortex of Wistar rats. Animals that were given repetitive injections of iron dextran for a total of 4 weeks showed a significant increase in lipid and protein markers such as thiobarbituric reactive acid substances, protein carbonyl product content levels, and DNA apoptosis in the cerebral cortex. These changes were accompanied by a decrease of enzymatic antioxidants like superoxide dismutase and catalase and in the levels of nonenzymatic antioxidants like total thiols and ascorbic acid. The activity of glutathione peroxidase remained unchanged in rats. A significant decrease in acetylcholinesterase and Na(+)/K(+)-ATPase activities was also shown, with a substantial rise in the nitric oxide levels. Coadministration of NGEN to iron-treated rats significantly improved antioxidant enzyme activities and attenuated oxidative damages observed in the cerebral cortex. The potential effect of NGEN to prevent iron-induced neurotoxicity was also reflected by the microscopic study, indicative of its neuroprotective effects.
authors.affiliation: Toxicology-Microbiology and Environmental Health (UR11ES70), Faculty of Sciences, University of Sfax, BP1171, 3000, Sfax, Tunisia, yacine_chtourou@yahoo.fr.
authors.forename: Yassine
authors.initials: Y
authors.lastname: Chtourou
authors.forename: Hamadi
authors.initials: H
authors.lastname: Fetoui
authors.forename: Radhouane
authors.initials: R
authors.lastname: Gdoura
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001205:Ascorbic Acid / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D053938:DNA Fragmentation / Q000187:drug effects; D044950:Flavanones / Q000494:pharmacology*; D019190:Iron Overload / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020258:Neurotoxicity Syndromes / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects*; D050050:Protein Carbonylation / Q000187:drug effects; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D044950:Flavanones; D018696:Neuroprotective Agents; D013438:Sulfhydryl Compounds; D017392:Thiobarbituric Acid Reactive Substances; D002374:Catalase; D013482:Superoxide Dismutase; D000110:Acetylcholinesterase; D000254:Sodium-Potassium-Exchanging ATPase; C005273:naringenin; D001205:Ascorbic Acid