High doses of vitamin E improve mitochondrial dysfunction in rat hippocampus and frontal cortex upon aging

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 O2− and H2O2 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 O2− and H2O2 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.Fil: Navarro, Ana. Universidad de Cádiz; EspañaFil: Bández, Manuel J.. Universidad de Cádiz; EspañaFil: López Cepero, José M.. Universidad de Cádiz; EspañaFil: Gómez, Carmen. Universidad de Cádiz; EspañaFil: Boveris, Alejandro D.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Cadenas, Enrique. University Of Southern California; Estados UnidosFil: Boveris, Alberto Antonio. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin