Aim: 

The Cu, Zn superoxide dismutase (SOD1) mutation found in some patients with familial amyotrophic lateral sclerosis (FALS) has been shown to result in an increase in free radical production that may cause systemic oxidative injury. In this study, we analyzed the extent of lipid and protein oxidative damage to the brain, heart, liver, muscle and spinal cord of transgenic FALS mice that overexpress the SOD1 mutation (G93A).

Methods: 

Fifty G93A mice were distributed into four groups according to age and SOD1 mutation: 40 and 100 day old mice without mutation (Control40 and Control100), 40 day old transgenic mice (FALS40) and 100 day old transgenic mice (FALS100). Malondialdehyde (MDA) + 4-hydroxyalkenals (4-HDA) concentrations and cabonilation of proteins were stimated as indices of lipid and protein peroxidation respectively.

Results: 

In FALS40 animals, MDA+4-HDA and protein carbonylation showed similar oxidative stress levels to the Control40. However, FALS100 mice showed that a MDA+4-HDA content in spinal cord significantly increased (p<0.05) compared with Control100 group. Moreover, MDA+4-HDA concentrations in this tissue were 2.5 times higher in FALS100 than in FALS40 (p<0.05). Although unhealthy old animals showed a higher level of lipid peroxidation in brain, muscle, heart and liver than old controls, no significant differences were found. Furthermore, protein oxidation increased in all organs in FALS100 in contrast to healthy mice.

Conclusion: 

These results suggest that the overproduction of free radical production caused by the G93A SOD 1 mutation lead to extensive lipid and protein systemic damage, above all in spinal cord, which could deteriorate its function.