D-galactose effectiveness in modeling aging and therapeutic antioxidant treatment in mice.

Accumulating evidence suggests that mitochondrial dysfunction and oxidative stress play major roles in aging. Chronic administration of D-galactose has been reported to cause deterioration of cognitive and motor skills that are similar to symptoms of aging and, therefore, is regarded as a model of accelerated aging. Because enhancing endogenous antioxidants is now widely regarded as an attractive therapy for conditions associated with mitochondrial oxidative stress, in the present study the effects of alpha-lipoic acid, L-carnitine, and PMX-500F on D-galactose treated mice were tested. Female mice were injected with (100 mg/kg) D-(+)-galactose for 6 weeks and some groups were treated with a daily dose of alpha-lipoic acid (5 mg/kg), L-carnitine (3.9 mg/kg), PMX-500F (11.9 mg/kg), or the vehicle (0.1M Tris, pH 7.4). Control mice were treated with physiological saline. An accelerating Rota-Rod, open field test, and Y-maze test were performed, and serum lactate concentrations were analyzed. These analyses did not identify impairment in motor coordination, open-field activity, or spatial memory (p>0.05). Similarly, serum lactate concentrations in D-galactose-treated mice were not elevated when compared to controls (p>0.05). Treatment with the antioxidant compounds at the given concentrations did not result in any changes in the behavioral parameters tested. In conclusion, results of this study illustrate that chronic, short-term D-galactose treatment may not represent a suitable model for inducing readily detectable age-related neurobehavioral symptoms in mice.