Blood oxidative stress in amyotrophic lateral sclerosis

Abstract

It has been suggested that amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder resulting in motor neuron death, is associated with oxidative damage induced by free radicals. Our study aimed to get an assessment of the blood oxidative stress status in a population of 167 ALS patients (aged 59±13 years), treated or not with riluzole, compared with 62 age-matched healthy control subjects (aged 60±11 years) simultaneously included in the study. We determined the level of plasma lipid peroxidation (thiobarbituric acid-reactive substances, TBARS); the status of the major lipophilic plasma antioxidant defenses (vitamin E, vitamin A and β-carotene); the activities of erythrocyte Cu,Zn-superoxide dismutase (Cu,Zn-SOD) and of plasma and erythrocyte glutathione peroxidase (GSH-Px). Plasma selenium was also determined as a trace element essential to the activity of the GSH-Px. In comparison with controls, we observed in ALS patients (mean±S.D.) significantly higher TBARS values (ALS=1.34±0.28 μmol/l; controls=1.11±0.20 μmol/l) and a significant enhancement of the erythrocyte SOD activity (ALS=710±114 U/g Hb; controls=667±93 U/g Hb). No differences were observed for selenium level, GSH-Px activity, plasma vitamin E, β-carotene and vitamin A concentrations. These data confirm the presence of an oxidative stress in blood of ALS patients. The elevated plasma TBARS, without any deficiency in plasma lipophilic antioxidants such as vitamin E, vitamin A and β-carotene, suggest an enhancement in the production of free radicals. No correlation was found in our study between the level of any of the blood oxidative stress markers and the disease duration. Comparison between patients treated or not with riluzole did not display any modification of the plasma TBARS concentration, but we observed a slight decrease of erythrocyte SOD activity in treated patients (treated=705±113 U/g Hb; not treated=725±118 U/g Hb), suggesting a possible activity of riluzole on the oxygenated free radical production.