title: D-galactose effectiveness in modeling aging and therapeutic antioxidant treatment in mice.
abstract: 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 α-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 α-lipoic acid (5 mg/kg), L-carnitine (3.9 mg/kg), PMX-500F (11.9 mg/kg), or the vehicle (0.1 M 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.
authors.affiliation: Department of Pathobiology, College of Veterinary Medicine, Auburn University, Alabama 36849-5112, USA.
authors.forename: Kodeeswaran
authors.initials: K
authors.lastname: Parameshwaran
authors.forename: Michael H
authors.initials: MH
authors.lastname: Irwin
authors.forename: Kosta
authors.initials: K
authors.lastname: Steliou
authors.forename: Carl A
authors.initials: CA
authors.lastname: Pinkert
mesh_terms: D000375:Aging / Q000097:blood / Q000187:drug effects*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D005260:Female; D005690:Galactose / Q000494:pharmacology*; D019344:Lactic Acid / Q000097:blood; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009043:Motor Activity / Q000187:drug effects; D045442:Rotarod Performance Test
chemical_list: D000975:Antioxidants; D019344:Lactic Acid; D005690:Galactose