Antioxidant strategies based on tomato-enriched food or pyruvate do not affect disease onset and survival in an animal model of amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder which is mostly sporadic, although about 5-10% of the cases are inherited. About 15-20% of patients with familial ALS (FALS) carry mutations in the gene encoding the free radical scavenging enzyme Cu/Zn superoxide dismutase (SOD1). In this study, we explored the potential neuroprotective effects of antioxidant strategies based on either a tomato-enriched diet, or pyruvate administration, in an animal model of ALS. To that aim, transgenic mice expressing a mutant form of SOD1 [the gly(93) --> ala (G93A) substitution; G93A SOD1] were fed on either tomato-enriched food pellets or the Altromin diet in which milk serum and proteins substitute for soy and fish flours. In both cases, treatments were started at the 29th day of age. In a second set of experiments, G93A SOD1 mice were treated with pyruvate intraperitoneally (500 mg/kg, i.p; starting at the 70th day of age) and compared with control mice receiving i.p. saline injections. Our results indicate that neither the tomato-enriched diet nor pyruvate administration caused any significant effect on the overall survival time and disease onset in G93A SOD1 mice. Thus, despite the wealth of data indicating the relevant role of oxidative stress and defective energy homeostasis both in patients and animal models of ALS, antioxidant strategies based on tomato-enriched food or pyruvate seem to be not sufficient to promote a disease modifying effect in an animal model of ALS.
Esposito
Ennio
E
Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro (Chieti), Italy.
Capasso
Margherita
M
di Tomasso
Nora
N
Corona
Carlo
C
Pellegrini
Fabio
F
Uncini
Antonino
A
Vitaglione
Paola
P
Fogliano
Vincenzo
V
Piantelli
Mauro
M
Sensi
Stefano L
SL
D017668:Age of Onset; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood / Q000401:mortality / Q000628:therapy*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D002338:Carotenoids / Q000097:blood; D004195:Disease Models, Animal; D005419:Flavonoids / Q000097:blood; D005527:Food, Fortified; D006801:Humans; D018551:Solanum lycopersicum; D051379:Mice; D008822:Mice, Transgenic; D019289:Pyruvic Acid / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000235:genetics; D016019:Survival Analysis
D000975:Antioxidants; D005419:Flavonoids; D002338:Carotenoids; D019289:Pyruvic Acid; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase