title: High doses of vitamin E improve mitochondrial dysfunction in rat hippocampus and frontal cortex upon aging.
abstract: Rat aging from 4 to 12 mo was accompanied by hippocampus and frontal cortex mitochondrial dysfunction, with decreases of 23 to 53% in tissue and mitochondrial respiration and in the activities of complexes I and IV and of mitochondrial nitric oxide synthase (mtNOS) (P < 0.02). In aged rats, the two brain areas showed mitochondria with higher content (35-78%) of oxidation products of phospholipids and proteins and with higher (59-95%) rates of O(2)(-) and H(2)O(2) production (P < 0.02). Dietary supplementation with vitamin E (2.0 or 5.0 g/kg of food) from 9 to 12 mo of rat age, restored in a dose-dependent manner, the decreases in tissue and mitochondrial respiration (to 90-96%) and complexes I and IV and mtNOS activities (to 86-88%) of the values of 4-mo-old rats (P < 0.02). Vitamin E prevented, by 73-80%, the increases in oxidation products, and by 62-68%, the increases in O(2)(-) and H(2)O(2) production (P < 0.05). High resolution histochemistry of cytochrome oxidase in the hippocampal CA1 region showed higher staining in vitamin E-treated rats than in control animals. Aging decreased (19%) hippocampus mitochondrial mass, an effect that was restored by vitamin E. High doses of vitamin E seem to sustain mitochondrial biogenesis in synaptic areas.
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Cádiz, Cádiz, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Navarro
authors.forename: Manuel J
authors.initials: MJ
authors.lastname: Bandez
authors.forename: Jose M
authors.initials: JM
authors.lastname: Lopez-Cepero
authors.forename: Carmen
authors.initials: C
authors.lastname: Gómez
authors.forename: Alberto
authors.initials: A
authors.lastname: Boveris
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D003576:Electron Transport Complex IV / Q000378:metabolism; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D023421:Models, Animal; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014810:Vitamin E / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D014810:Vitamin E; D006861:Hydrogen Peroxide; D019001:Nitric Oxide Synthase; D003576:Electron Transport Complex IV; D010100:Oxygen