Dual effect of docosahexaenoic acid (attenuation or amplification) on C22:0-, C24:0-, and C26:0-induced mitochondrial dysfunctions and oxidative stress on human neuronal SK-N-BE cells.

Increased levels of C22:0, C24:0 and C26:0 were found in cortical lesions of patients with Alzheimer's disease (AD). So, it was of interest to precise the cytotoxic effects of these fatty acids, and to determine whether docosahexaenoic acid (DHA), described to prevent AD, can attenuate their eventual side effects. Human neuronal SK-N-BE cells were cultured in the absence or presence of C22:0, C24:0 or C26:0 (0.1-20 µM) without or with DHA (50-150 µM). C22:0, C24:0 and C26:0 induce an inhibition of cell growth, a loss of Δψm, an overproduction of reactive oxygen species (ROS), a decrease of reduced glutathione, and a lipid peroxidation. DHA attenuates C22:0, C24:0 and C26:0 induced-mitochondrial dysfunctions and/or cell growth inhibition measured with MTT whatever the concentrations considered, whereas it can either decrease or amplify (especially at 150 µM) ROS overproduction. C22:0, C24:0 and C26:0 have neurotoxic activities, and depending on its concentration, DHA attenuates or not fatty acid-induced side effects.