title: Naringenin Mitigates Iron-Induced Anxiety-Like Behavioral Impairment, Mitochondrial Dysfunctions, Ectonucleotidases and Acetylcholinesterase Alteration Activities in Rat Hippocampus.
abstract: Studies demonstrated that the iron chelating antioxidant restores brain dysfunction induced by iron toxicity in animals. Earlier, we found that iron overload-induced cerebral cortex apoptosis correlated with oxidative stress could be protected by naringenin (NGEN). In this respect, the present study is focused on the mechanisms associated with the protective efficacy of NGEN, natural flavonoid compound abundant in the peels of citrus fruit, on iron induced impairment of the anxiogenic-like behaviour, purinergic and cholinergic dysfunctions with oxidative stress related disorders on mitochondrial function in the rat hippocampus. Results showed that administration of NGEN (50 mg/kg/day) by gavage significantly ameliorated anxiogenic-like behaviour impairment induced by the exposure to 50 mg of Fe-dextran/kg/day intraperitoneally for 28 days in rats, decreased iron-induced reactive oxygen species formation and restored the iron-induced decrease of the acetylcholinesterase expression level, mitochondrial membrane potential and mitochondrial complexes activities in the hippocampus of rats. Moreover, NGEN was able to restore the alteration on the activity and expression of ectonucleotidases such as adenosine triphosphate diphosphohydrolase and 5'-nucleotidase, enzymes which hydrolyze and therefore control extracellular ATP and adenosine concentrations in the synaptic cleft. These results may contribute to a better understanding of the neuroprotective role of NGEN, emphasizing the influence of including this flavonoid in the diet for human health, possibly preventing brain injury associated with iron overload.
authors.affiliation: Toxicology-Microbiology and Environmental Health Unit (UR11ES70), Life Sciences Department, Faculty of Sciences, University of Sfax, Street Soukra Km 3.5, BP 1171, 3000, Sfax, Tunisia, yacine_chtourou@topnet.tn.
authors.forename: Yassine
authors.initials: Y
authors.lastname: Chtourou
authors.forename: Ahlem Ben
authors.initials: AB
authors.lastname: Slima
authors.forename: Radhouane
authors.initials: R
authors.lastname: Gdoura
authors.forename: Hamadi
authors.initials: H
authors.lastname: Fetoui
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D044950:Flavanones / Q000494:pharmacology / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007501:Iron / Q000633:toxicity*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D044950:Flavanones; D007501:Iron; D000110:Acetylcholinesterase; D000251:Adenosine Triphosphatases; C027201:ectoATPase; C005273:naringenin