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Vol. 40. Núm. 4.
Páginas 235-242 (Agosto 2005)
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Vol. 40. Núm. 4.
Páginas 235-242 (Agosto 2005)
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Efecto de dos antioxidantes en la supervivencia, las actividades neurológicas y la función mitocondrial de ratones senescentes
Effect of two antioxidants on survival, neurological activities and mitochondrial function in senescent mice
Visitas
4380
A. Navarroa,
Autor para correspondencia
ana.navarro@uca.es

Correspondencia: Prof. A. Navarro. Departamento de Bioquímica y Biología Molecular. Facultad de Medicina. P.° Fragela, 9. 11003 Cádiz. España.
, M.J. Bándeza, C. Gómeza, H. Gonzáleza, N. Escuderoa, J.C. García-Ortiza, J.F. Carrióna, M.J. Sánchez-Pinoa, J.M. López-Ceperob
a Departamento de Bioquímica y Biología Molecular. Facultad de Medicina. Universidad de Cádiz. Cádiz. España
b Departamento de Histología. Facultad de Medicina. Universidad de Cádiz. Cádiz. España
Este artículo ha recibido
Información del artículo
Resumen
Objetivos

Valorar la influencia de tratamientos crónicos con los antioxidantes vitamina E y tioprolina en: a) la supervivencia de ratones; b) la actividad neurológica de los animales envejecidos, y c) la disminución de actividades enzimáticas mitocondriales y el daño oxidativo mitocondrial asociados al proceso de envejecimiento.

Material y método

Los ratones recibieron desde la semana 28 de vida, y durante toda su vida, una suplementación en la dieta de vitamina E (5 g de acetato de dl-α-tocoferol/kg de comida) o de tioprolina (2 g de l-4-ácido tiazolidín carboxílico/kg de comida). Para evaluar la actividad neurológica los ratones se sometieron cada 2 semanas a 2 pruebas de comportamiento. En mitocondrias aisladas de cerebro se determinó el daño oxidativo, medido como proteínas o lípidos oxidados, así como por disminución de las actividades enzimáticas NADH-citocromo c reductasa, succinatocitocromo c reductasa, citocromo oxidasa y óxido nítrico sintasa mitocondrial (mtNOS).

Resultados

La expectativa de vida de los ratones macho aumentó después de la suplementación con vitamina E en un 34-34% (vida media y longevidad máxima, respectivamente), y después de la suplementación con tioprolina en un 33-24%. La vitamina E y la tioprolina fueron efectivas en la disminución de los marcadores mitocondriales de daño oxidativo (TBARS y carbonilos proteínicos), y en el retardo de la disminución de las actividades enzimáticas y neurológicas asociadas al envejecimiento.

Conclusiones

Las actividades enzimáticas de mtNOS, NADH deshidrogenasa y citocromo oxidasa pueden usarse como indicadores de tratamientos efectivos del déficit neurológico asociado al envejecimiento.

Palabras clave:
Envejecimiento
Estrés oxidativo
Actividad neurológica
Vitamina E
Tioprolina
Mitocondria
MtNOS
NADH deshidrogenasa
Citocromo oxidasa
Abstract
Aims

The aim of this study was to evaluate the influence of chronic treatments with the antioxidants vitamin E and thioproline on: 1) survival in mice; 2) the neurological activities of aged animals; and 3) the decreased mitochondrial enzymatic activities and oxidative damage associated with the ageing process.

Material and method

Mice received food upplemented with vitamin E (5 g dl-α-tocopherol acetate/kg of food) or with thioproline l-4-thioproline/kg (2 g l-4-thiazolidine carboxylic acid/kg of food) from 28 weeks of age and during their entire lifespan. To evaluate neurological activity the animals underwent two behavioural tests every 15 days from weeks 28 to 76 of age. Oxidative damage to isolated brain mitochondria was evaluated by determining protein and lipid oxidation products and mitochondrial enzyme activities: NADH-cytochrome c reductase, succinate-cytochrome c reductase, cytochrome oxidase, and mitochondrial nitric oxide synthase (mtNOS).

Results

Lifespan was increased in male mice by 34-34% (mean and maximal lifespan, respectively) after supplementation with 5 g vitamin E/kg food and by 33-24% (mean and maximal lifespan, respectively) after supplementation with 2 g thioproline/kg food. Vitamin E and thioproline were effective in decreasing the level of markers of oxidative damage (TBARS and protein carbonyls) in isolated mitochondria and in delaying the decreases in mitochondrial enzyme activities and the loss of neurological function associated with ageing.

Conclusions

The activities of mtNOS, NADH dehydrogenase and cytochrome oxidase can be used as indicators of the effectiveness of treatments for age-dependent neurological impairment.

Key words:
Ageing
Oxidative stress
Neurological activity
Vitamin E
Thioproline
Mitochondria
MtNOS
NADH-dehydrogenase
Cytochrome oxidase
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Este estudio ha sido financiado por los proyectos FIS 99-1033 y 02-1354 del Ministerio de Sanidad y Consumo de España, y por el Plan Andaluz de Investigación 2000-03 (CTS-194).

Copyright © 2005. Sociedad Española de Geriatría y Gerontología
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