Monitoring systemic oxidative stress in an animal model of amyotrophic lateral sclerosis.
A mutant form of the ubiquitous copper/zinc superoxide dismutase (SOD1) protein has been found in some patients with amyotrophic lateral sclerosis (ALS). We monitored oxidative stress in an animal model of ALS, the SOD(G93A) mouse, which develops a disease similar to ALS with an accelerated course. The aim of this work was to show that ALS damages several organs and tissues, from an oxidative stress point of view. We measured lipid and protein oxidative damage in different tissue homogenates of SOD(G93A) mice. The biomarkers that we analyzed were malondialdehyde + 4-hydroxyalkenal (MDA + 4-HDA) and carbonyls, respectively. The spinal cord and brain of SOD(G93A) mice showed increased lipid peroxidation after 100 or 130 days compared to age-matched littermate controls. The CNS was most affected, but lipid peroxidation was also detected in the skeletal muscle and liver on day 130. No changes were observed in protein carbonylation in the homogenates. Our results are consistent with a multisystem etiology of ALS and suggest that oxidative stress may play a primary role in ALS pathogenesis. Thus, oxidative stress represents a potential biomarker that might be useful in developing new therapeutic strategies for ALS.
Departamento Farmacología y Fisiología, Universidad de Zaragoza, c) Domingo Miral s/n, 50009, Zaragoza, Spain.
Francisco Javier
FJ
Miana-Mena
Cristina
C
González-Mingot
Pilar
P
Larrodé
María Jesús
MJ
Muñoz
Sara
S
Oliván
Lorena
L
Fuentes-Broto
Enrique
E
Martínez-Ballarín
Russel J
RJ
Reiter
Rosario
R
Osta
Joaquín José
JJ
García
D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D004195:Disease Models, Animal; D015227:Lipid Peroxidation / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress / Q000502:physiology*